Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

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2017-10-01

AWARD NUMBERS: W81XWH-14-1-0554 TITLE: Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer PRINCIPAL INVESTIGATOR...Dr. Nora M. Navone CONTRACTING ORGANIZATION: The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd. Houston, TX 77030-4009...COVERED 09/22/2016-09/21/2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER N/A Development of Personalized Cancer Therapy for Men with Advanced

Radiation therapy for prostate cancer.

Science.gov (United States)

Koontz, Bridget F; Lee, W Robert

2013-07-01

Radiation therapy is an effective treatment for newly diagnosed prostate cancer, salvage treatment, or for palliation of advanced disease. Herein we briefly discuss the indications, results, and complications associated with brachytherapy and external beam radiotherapy, when used as monotherapy and in combination with each other or androgen deprivation. Copyright © 2013 Elsevier Inc. All rights reserved.

MRI-guided biopsies and minimally invasive therapy for prostate cancer

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Sangeet Ghai

2015-01-01

Full Text Available Recent advances in multiparametric magnetic resonance imaging (mp-MRI have led to a paradigm shift in the diagnosis and management of prostate cancer (PCa. Its sensitivity in detecting clinically significant cancer and the ability to localize the tumor within the prostate gland has opened up discussion on targeted diagnosis and therapy in PCa. Use of mp-MRI in conjunction with prostate-specific antigen followed by targeted biopsy allows for a better diagnostic pathway than transrectal ultrasound (TRUS biopsy and improves the diagnosis of PCa. Improved detection of PCa by mp-MRI has also opened up opportunities for focal therapy within the organ while reducing the incidence of side-effects associated with the radical treatment methods for PCa. This review discusses the evidence and techniques for in-bore MRI-guided prostate biopsy and provides an update on the status of MRI-guided targeted focal therapy in PCa.

Percutaneous radiation therapy for localized and generalized stages of prostatic cancer

International Nuclear Information System (INIS)

Mueller, R.P.; Schnepper, E.; Castrup, W.

1981-01-01

Eighty-three patients with prostatic cancer, who underwent megavoltage therapy of the carcinoma or of its metastases, are reported. The majority of the patients had advanced disease (Stage C or D according to Flocks) when they came to be treated, and thus the general prognosis was bad. Radiation therapy, however, represents on the whole an important constituent of therapy in prostatic cancer, with regard to the practicability as well as to palliative treatment of metastases to the skeleton. (orig.) [de

The role of metastasis-directed therapy and local therapy of the primary tumor in the management of oligometastatic prostate cancer.

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Kim, Jongchan; Park, Jee Soo; Ham, Won Sik

2017-09-01

Oligometastasis has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastasis. Oligometastatic malignancy is now being diagnosed more frequently as the result of improvements in diagnostic modalities such as functional imaging. The importance of oligometastasis in managing metastatic prostate cancer is that it is possible to treat with a curative aim by metastasis-directed or local therapy in selected patients. Many studies have shown that these aggressive treatments lead to improved survival in other oligometastatic malignancies. However, few studies have shown definitive benefits of metastasis-directed or local therapy in oligometastatic prostate cancer. Review of the available studies suggests that stereotactic radiotherapy (RT) of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing oligometastatic prostate cancer. Also, stereotactic RT can delay the start of androgen deprivation therapy. Many retrospective studies of metastatic prostate cancer have shown that patients undergoing local therapy seem to have superior overall and cancer-specific survival compared with patients not receiving local therapy. Ongoing prospective randomized trials would be helpful to evaluate the role of local therapy in oligometastatic prostate cancer.

The role of metastasis-directed therapy and local therapy of the primary tumor in the management of oligometastatic prostate cancer

Directory of Open Access Journals (Sweden)

Jongchan Kim

2017-09-01

Full Text Available Oligometastasis has been proposed as an intermediate stage of cancer spread between localized disease and widespread metas-tasis. Oligometastatic malignancy is now being diagnosed more frequently as the result of improvements in diagnostic modalities such as functional imaging. The importance of oligometastasis in managing metastatic prostate cancer is that it is possible to treat with a curative aim by metastasis-directed or local therapy in selected patients. Many studies have shown that these aggressive treatments lead to improved survival in other oligometastatic malignancies. However, few studies have shown definitive benefits of metastasis-directed or local therapy in oligometastatic prostate cancer. Review of the available studies suggests that stereotac-tic radiotherapy (RT of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing oligometastatic prostate cancer. Also, stereotactic RT can delay the start of androgen deprivation therapy. Many retrospective studies of metastatic prostate cancer have shown that patients undergoing local therapy seem to have superior overall and cancer-specific survival compared with patients not receiving local therapy. Ongoing prospective randomized trials would be helpful to evaluate the role of local therapy in oligometastatic prostate cancer.

Overall Survival Benefit From Postoperative Radiation Therapy for Organ-Confined, Margin-Positive Prostate Cancer

International Nuclear Information System (INIS)

Dillman, Robert O.; Hafer, Russell; Cox, Craig; McClure, Stephanie E.

2011-01-01

Purpose: Radical prostatectomy for invasive prostate cancer is associated with positive margin rates in 10% to 50% of resected specimens. Postoperative radiation therapy may benefit patients who have organ-confined prostate cancer with positive margins. Methods and Materials: We performed a retrospective analysis to examine whether adjunctive radiation therapy enhanced long-term survival for prostate cancer patients who underwent prostatectomy for localized prostate cancer but with positive margins. We used the Hoag Cancer Center database to identify patients diagnosed with invasive prostate cancer. Relative and overall survival rates were calculated. Results: Among 1,474 patients diagnosed with localized invasive prostate cancer during the years 1990 to 2006 and undergoing prostatectomy, 113 (7.7%) were identified who had positive margins and did not have local extension of disease, positive lymph nodes, or distant metastases. A total of 17 patients received adjunctive radiation therapy (Group A), whereas 96 did not (Group B; 3 received hormonal therapy). Both groups had a median age of 64 years and median follow-up of 7.5 years. In Group A, no patients have died as of last follow-up, but in Group B, 18 have died. Estimated 10-year and 15-year overall survival rates were both 100% for Group A compared with 85% and 57% respectively for Group B (p 2 = 0.050, log rank). Relative 10- and 15 year survival rates were both 100% for Group A compared with 100% and 79% respectively for Group B. Conclusions: This retrospective analysis suggests that prostate cancer patients with localized disease but positive margins do derive a survival benefit from adjuvant radiation therapy.

Cannabinoid Receptors: A Novel Target for Therapy of Prostate Cancer

Science.gov (United States)

2007-02-01

study could be to develop nonhabit-forming cannabi - noid agonist (s) for the management of prostate cancer . REFERENCES 1. Jemal, A., Siegel, R.W...for Therapy of Prostate Cancer PRINCIPAL INVESTIGATOR: Prof. Hasan Mukhtar, Ph.D (PI) Dr. Farrukh Afaq, Ph.D (Co-Investigator...REPORT DATE: February 2007 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command

Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer

Science.gov (United States)

2011-05-01

8 4 INTRODUCTION The focus of this project is to evaluate the anti-tumor effects of benzimidazoles as a...potential anti-metastatic prostate cancer therapy. We identified benzimidazoles , a class of anti-parasitic drug, in a drug screening process for...preferential anti-tumor activity on metastatic prostate cancer cells. We have data indicate that benzimidazoles have potent anti-tumor activities

Endocrine therapy for recurrence after definitive radiotherapy in patients with prostate cancer

International Nuclear Information System (INIS)

Furuya, Yuzo; Akakura, Koichiro; Ichikawa, Tomohiko; Igarashi, Tatsuo; Ito, Haruo; Tanaka, Masashi; Murakami, Shino

2001-01-01

Long-term results were analyzed to evaluate the role of endocrine therapy in the management of local and distant recurrence of prostate cancer following external radiation therapy. Between 1976 and 1994, 92 patients with untreated prostate cancer underwent external beam radiation therapy alone. Endocrine therapy had been started when relapse was evident. Failure was seen in 35 of 92 patients: 10 local, 19 distant and six biochemical failures. Endocrine treatment was performed in 28 patients with nine local and 19 distant failures. The cancer-specific survival rate from the endocrine treatment was 54.5% at 5 years. Prostate-specific antigen level in 20 of 20 patients (100%) decreased to below the normal limit 3 months after the start of endocrine therapy. In univariate analysis, T classification was the most significant variable for cancer-specific survival from the initial treatment. A favorable outcome was achieved by endocrine therapy in patients who had relapsed after external beam radiation monotherapy. Even the recurrent tumor had a sensitivity to androgen. Patients with locally advanced disease (T2b and T3) had poorer prognosis than those with minimally extended disease (T1b and T2a). (author)

Saw Palmetto for Symptom Management During Radiation Therapy for Prostate Cancer.

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Wyatt, Gwen K; Sikorskii, Alla; Safikhani, Abolfazl; McVary, Kevin T; Herman, James

2016-06-01

Lower urinary tract symptoms (LUTSs) affect 75%-80% of men undergoing radiation therapy (RT) for prostate cancer. To determine the safety, maximum tolerated dose (MTD), and preliminary efficacy of Serenoa repens commonly known as saw palmetto (SP) for management of LUTS during RT for prostate cancer. The dose finding phase used the time-to-event continual reassessment method to evaluate safety of three doses (320, 640, and 960 mg) of SP. Dose-limiting toxicities were assessed for 22 weeks using the Common Terminology Criteria for Adverse Events for nausea, gastritis, and anorexia. The exploratory randomized controlled trial phase assessed preliminary efficacy of the MTD against placebo. The primary outcome of LUTS was measured over 22 weeks using the International Prostate Symptom Score. Additional longitudinal assessments included quality of life measured with the Functional Assessment of Cancer Therapy-Prostate. The dose finding phase was completed by 27 men who reported no dose-limiting toxicities and with 20 participants at the MTD of 960 mg daily. The exploratory randomized controlled trial phase included 21 men, and no statistically significant differences in the International Prostate Symptom Score were observed. The prostate-specific concerns score of the Functional Assessment of Cancer Therapy-Prostate improved in the SP group (P = 0.03). Of 11 men in the placebo group, two received physician-prescribed medications to manage LUTS compared with none of the 10 men in the SP group. SP at 960 mg may be a safe herbal supplement, but its efficacy in managing LUTS during RT needs further investigation. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Nuclear Imaging for Assessment of Prostate Cancer Gene Therapy

Science.gov (United States)

2007-03-01

thymidine kinase transfected EL4 cells . Further exploration of Tc-99m conjugated potential HSV1-TK substrates is still undergoing in our laboratory...prostate cancer cells , has been demonstrated the utility for tissue-specific toxic gene therapy for prostate cancer[10, 11]. Therefore, an adenovirus...BJ5183 together with pAdeasy-1, the viral DNA plasmid. The pAdeasy-1 is E1 and E3 deleted, its E1 function can be complemented in 293A cells . The

Radiation therapy for prostatic cancer

International Nuclear Information System (INIS)

Kimura, Akira; Minowada, Shigeru; Tomoishi, Junzo; Kinoshita, Kenji; Matsuda, Tadayoshi

1983-01-01

A conformation radiotherapy system with collimators, whose openings can be controlled symmetrically by computerized techniques during rotational irradiation by a linear accelerator, has been developed for routine use in our hospital. Forty-four patients underwent radiation therapy, including this particular modality of radiotherapy, for prostatic cancer during the period of July 1976 through December 1981. Eight patients were classified as stage A, 10 stage B, 10 stage C, and 16 as stage D. Twenty-nine patients underwent conformation radiotherapy, two rotation radiotherapy, eight 2-port opposing technique radiotherapy, one 4-field radiotherapy, and four underwent a combination of 2-port opposing technique and conformation radiotherapy. Transient mild side effects such as diarrhea occurred in seven cases, while severe side effects such as rectal stricture or contracted bladder occurred in three cases. The latter occurred only in one case among 29 of conformation radiotherapy and in two among eight of 2-port opposing technique radiotherapy. The results of the treatment of short intervals in stage B, C, and D are as follows: prostatic size was reduced in 26 cases among 36, serum acid phosphatase level was reduced in 15 among 18 who had showed high acid phosphatase levels before treatment, although almost all cases underwent simultaneous hormonal therapy. The effects of radiotherapy alone were verified in two cases of stage B in which radiotherapy preceded hormonal therapy. Prostatic size and serum acid phosphatase level were reduced by radiotherapy alone. (author)

Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol.

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Baguley, Brenton J; Skinner, Tina L; Leveritt, Michael D; Wright, Olivia R L

2017-01-03

Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse side effects of treatment. The exercise literature has shown high intensity interval training can improve various aspects of health that are typically impaired with androgen deprivation therapy; however exercise at this intensity is yet to be conducted in men with prostate cancer. The purpose of this study is to examine the effects of nutrition therapy beyond the current healthy eating guidelines with high intensity interval training for managing cancer-related fatigue in men with prostate cancer treated with androgen deprivation therapy. This is a two-arm randomized control trial of 116 men with prostate cancer and survivors treated with androgen deprivation therapy. Participants will be randomized to either the intervention group i.e. nutrition therapy and high intensity interval training, or usual care. The intervention group will receive 20 weeks of individualized nutrition therapy from an Accredited Practising Dietitian, and high intensity interval training (from weeks 12-20 of the intervention) from an Accredited Exercise Physiologist. The usual care group will maintain their standard treatment regimen over the 20 weeks. Both groups will undertake primary and secondary outcome testing at baseline, week 8, 12, and 20; testing includes questionnaires of fatigue and quality of life, objective measures of body composition, muscular strength, cardiorespiratory fitness, biomarkers for disease progression, as well as dietary analysis. The primary outcomes for this trial are measures of

Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy.

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Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

2013-01-01

The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization.

Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy

OpenAIRE

Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

2013-01-01

The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization.

Quality of Life in Men Treated With Carbon Ion Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Wakatsuki, Masaru; Tsuji, Hiroshi; Ishikawa, Hitoshi; Yanagi, Takeshi; Kamada, Tadashi; Nakano, Takashi; Suzuki, Hiroyoshi; Akakura, Koichiro; Shimazaki, Jun; Tsujii, Hirohiko

2008-01-01

Purpose: To prospectively assess patient quality of life (QOL) after carbon ion radiotherapy (C-ion RT) for prostate cancer, using established questionnaires. Methods and Material: The subjects were 150 patients who underwent C-ion RT. Of these, 25 patients with low-risk prostate cancer received C-ion RT alone, whereas the remaining 125 patients with a high-risk tumor also received androgen deprivation therapy. Quality of life was assessed using the self-administered Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire in all patients three times. In addition, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI) was conducted in the low-risk patients. Results: The FACT-General (FACT-G) and FACT-P scores at 12 months after treatment averaged over all 150 patients showed no significant change compared with those before C-ion RT. In FACT-P subscales, emotional well-being increased significantly just after and 12 months after treatment. In contrast, physical well-being (PWB) and social/family well-being (S/FWB) decreased significantly at 12 months, whereas the prostate cancer subscale (PCS) decreased significantly just after treatment. Average scores for FACT-G, FACT-P, PWB, S/FWB, and PCS for the 125 patients receiving hormone therapy showed substantial detrimental changes at 12 months. In contrast, those of the 25 low-risk patients who had no hormone therapy showed no significant change. Similarly no significant change in the average of the UCLA-PCI scores in the low-risk patients was seen at 12 months. Conclusions: Average QOL parameters reported by patients with localized prostate cancer treated with C-ion RT, in the absence of hormone therapy, showed no significant decrease 12 months after C-ion RT

Hormone therapy in metastatic prostate cancer

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Jebelameli P

1997-09-01

Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

Therapy assessment in prostate cancer using choline and PSMA PET/CT

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Ceci, Francesco; Castellucci, Paolo; Fanti, Stefano [University of Bologna, Nuclear Medicine Unit, S. Orsola-Malpighi University Hospital, Bologna (Italy); Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); University of California Los Angeles, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA (United States); Hadaschik, Boris [University Hospital Essen, Department of Urology, Essen (Germany)

2017-08-15

While PET with non-FDG tracers (mainly choline and Ga-PSMA) has commonly been used for restaging in men with biochemically recurrent prostate cancer, as well as for primary staging, it is only recently that a few preliminary studies have addressed the possible use of PET for monitoring the response to systemic therapy of metastatic disease, especially innovative treatments such as abiraterone and enzalutamide. This article aims to evaluate the role of PET imaging with different non-FDG radiotracers for assessment of therapy in advanced prostate cancer patients. (orig.)

Image Guidance Based on Prostate Position for Prostate Cancer Proton Therapy

International Nuclear Information System (INIS)

Vargas, Carlos; Wagner, Marcus; Indelicato, Daniel; Fryer, Amber; Horne, David; Chellini, Angela; McKenzie, Craig; Lawlor, Paula; Mahajan, Chaitali; Li Zuofeng; Lin Liyong; Keole, Sameer

2008-01-01

Purpose: To determine the target coverage for proton therapy with and without image guidance and daily prebeam reorientation. Methods and Materials: A total of 207 prostate positions were analyzed for 9 prostate cancer patients treated using our low-risk prostate proton therapy protocol (University of Florida Proton Therapy Institute 001). The planning target volume was defined as the prostate plus a 5-mm axial and 8-mm superoinferior extension. The prostate was repositioned using 5- and 10-mm shifts (anteriorly, inferiorly, posteriorly, and superiorly) and for Points A-D using a combination of 10-mm multidimensional movements (anteriorly or inferiorly; posteriorly or superiorly; and left or right). The beams were then realigned using the new prostate position. The prescription dose was 78 Gray equivalent (GE) to 95% of the planning target volume. Results: For small movements in the anterior, inferior, and posterior directions within the planning target volume (≤5 mm), treatment realignment demonstrated small, but significant, improvements in the clinical target volume (CTV) coverage to the prescribed dose (78 GE). The anterior and posterior shifts also significantly increased the minimal CTV dose (Δ +1.59 GE). For prostate 10-mm movements in the inferior, posterior, and superior directions, the beam realignment produced larger and significant improvements for both the CTV V 78 (Δ +6.4%) and the CTV minimal dose (Δ +8.22 GE). For the compounded 10-mm multidimensional shifts, realignment significantly improved the CTV V 78 (Δ +11.8%) and CTV minimal dose (Δ +23.6 GE). After realignment, the CTV minimal dose was >76.6 GE (>98%) for all points (A-D). Conclusion: Proton beam realignment after target shift will enhance CTV coverage for different prostate positions

T2-weighted endorectal magnetic resonance imaging of prostate cancer after external beam radiation therapy

International Nuclear Information System (INIS)

Westphalen, Antonio C.; Kurhanewicz, John; Cunha, Rui M.G.; Hsu, I-Chow; Kornak, John; Zhao, Shoujun; Coakley, Fergus V.

2009-01-01

Purpose: To retrospectively determine the accuracy of T2-weighted endorectal MR imaging in the detection of prostate cancer after external beam radiation therapy and to investigate the relationship between imaging accuracy and time since therapy. Materials and Methods: Institutional review board approval was obtained and the study was HIPPA compliant. We identified 59 patients who underwent 1.5 Tesla endorectal MR imaging of the prostate between 1999 and 2006 after definitive external beam radiation therapy for biopsy-proven prostate cancer. Two readers recorded the presence or absence of tumor on T2-weighted images. Logistic regression and Fisher's exact tests for 2x2 tables were used to determine the accuracy of imaging and investigate if accuracy differed between those imaged within 3 years of therapy (n = 25) and those imaged more than 3 years after therapy (n = 34). Transrectal biopsy was used as the standard of reference for the presence or absence of recurrent cancer. Results: Thirty-four of 59 patients (58%) had recurrent prostate cancer detected on biopsy. The overall accuracy of T2-weighted MR imaging in the detection cancer after external beam radiation therapy was 63% (37/59) for reader 1 and 71% for reader 2 (42/59). For both readers, logistic regression showed no difference in accuracy between those imaged within 3 years of therapy and those imaged more than 3 years after therapy (p = 0.86 for reader 1 and 0.44 for reader 2). Conclusion: T2-weighted endorectal MR imaging has low accuracy in the detection of prostate cancer after external beam radiation therapy, irrespective of the time since therapy. (author)

Focal Therapy in Prostate Cancer-Report from a Consensus Panel

NARCIS (Netherlands)

de la Rosette, J.; Ahmed, H.; Barentsz, J.; Johansen, T. Bjerklund; Brausi, M.; Emberton, M.; Frauscher, F.; Greene, D.; Harisinghani, M.; Haustermans, K.; Heidenreich, A.; Kovacs, G.; Mason, M.; Montironi, R.; Mouraviev, V.; de Reijke, T.; Taneja, S.; Thuroff, S.; Tombal, B.; Trachtenberg, J.; Wijkstra, H.; Polascik, T.

2010-01-01

Purpose: To establish a consensus in relation to case selection, conduct of therapy, and outcomes that are associated with focal therapy for men with localized prostate cancer. Material and Methods: Urologic surgeons, radiation oncologists, radiologists, and histopathologists from North America and

Focal therapy in prostate cancer-report from a consensus panel.

NARCIS (Netherlands)

Rosette, J.J.M.H.C. de la; Ahmed, H.; Barentsz, J.O.; Johansen, T.B.; Brausi, M.; Emberton, M.; Frauscher, F.; Greene, D.; Harisinghani, M.; Haustermans, K.; Heidenreich, A.; Kovacs, G.; Mason, M.; Montironi, R.; Mouraviev, V.; Reijke, T. de; Taneja, S.; Thuroff, S.; Tombal, B.; Trachtenberg, J.; Wijkstra, H.; Polascik, T.

2010-01-01

PURPOSE: To establish a consensus in relation to case selection, conduct of therapy, and outcomes that are associated with focal therapy for men with localized prostate cancer. MATERIAL AND METHODS: Urologic surgeons, radiation oncologists, radiologists, and histopathologists from North America and

Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

Directory of Open Access Journals (Sweden)

Shian-Ying Sung

Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

International Nuclear Information System (INIS)

Iwasawa, Toshihisa; Matsumoto, Hidetsugu

1996-01-01

To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

Management of Biochemical Recurrence after Primary Localized Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Darwish, Oussama M.; Raj, Ganesh V.

2012-01-01

Clinically localized prostate cancer is typically managed by well established therapies like radical prostatectomy, brachytherapy, and external beam radiation therapy. While many patients can be cured with definitive local therapy, some will have biochemical recurrence (BCR) of disease detected by a rising serum prostate-specific antigen (PSA). Management of these patients is nuanced and controversial. The natural history indicates that a majority of patients with BCR will not die from prostate cancer but from other causes. Despite this, a vast majority of patients with BCR are empirically treated with non-curable systemic androgen deprivation therapy (ADT), with its myriad of real and potential side effects. In this review article, we examined the very definition of BCR after definitive local therapy, the current status of imaging studies in its evaluation, the need for additional therapies, and the factors involved in the decision making in the choice of additional therapies. This review aims to help clinicians with the management of patients with BCR. The assessment of prognostic factors including absolute PSA level, time to recurrence, PSA kinetics, multivariable nomograms, imaging, and biopsy of the prostatic bed may help stratify the patients into localized or systemic recurrence. Patients with low-risk of systemic disease may be cured by a salvage local therapy, while those with higher risk of systemic disease may be offered the option of ADT or a clinical trial. An algorithm incorporating these factors is presented.

Radical radiation therapy for prostate cancer in Japan. A patterns of care study report

International Nuclear Information System (INIS)

Nakamura, Katsumasa; Mitsuhashi, Norio

2003-01-01

The patterns of radical radiation therapy for prostate cancer are unclear in Japan. A Patterns of Care Study was performed throughout Japan to examine the patterns of radiation therapy for prostate cancer. From 1999 to 2000, extramural audits were performed on 50 randomly selected institutions (∼7% of all institutions in Japan). Detailed information was collected on a total of 311 prostate cancer patients without evidence of distant metastases, who were treated by radiation therapy between 1996 and 1998. Of these 311 patients, 162 treated radically using photon beams were analyzed in this study. Eighty percent of the patients had high-risk diseases defined as T3 or T4 tumors, a pretreatment prostate-specific antigen level >20 ng/ml or poorly differentiated adenocarcinoma. Androgen ablation was performed in 85.8% of patients and the median duration of hormonal therapy before and after radiation therapy was 5.3 and 21.4 months, respectively. The median total dose of radiation therapy to the prostate was 65.0 Gy (range: 20-74 Gy). The 3-year overall and biochemical relapse-free survival rates were 86.7 and 86.1%, respectively. Late toxicity was mild, with only nine patients (5.6%) exhibiting grade 2 late morbidity. The majority of the patients who received radical radiation therapy in Japan have high-risk disease. Androgen ablation plus radiation therapy was commonly used to treat these patients and resulted in high rates of initial control with a low risk of complications. (author)

Late rectal symptoms and quality of life after conformal radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Geinitz, Hans; Zimmermann, Frank B.; Thamm, Reinhard; Erber, Caroline; Mueller, Tobias; Keller, Monika; Busch, Raymonde; Molls, Michael

2006-01-01

Background and purpose: This study was carried out in order to analyze the prevalence of late rectal and anal symptoms after conformal radiation therapy for prostate cancer and to assess their association with quality of life. Patients and methods: Two-hundred and forty nine patients were interviewed at 24-111 months after definitive conformal radiation therapy of localized prostate cancer with a median dose of 70 Gy. Rectal symptoms and fecal incontinence were evaluated with standardized questionnaires. Quality of life was assessed with the EORTC Quality of Life Questionnaire-C30 and the prostate cancer module PR25. Results: Rectal symptoms were mostly intermittent. Daily symptoms occurred in ≤5% of the patients. Incontinence was mostly mild with only 3% of the patients reporting daily incontinence episodes. Quality of life was comparable to that of the male German general population except that cognitive functioning and diarrhea were worse in the study population and pain was worse in the reference population. Global quality of life was associated with fecal incontinence, fecal urge, tenesmus, therapy for rectal symptoms and hormonal therapy for biochemical/clinical recurrence. Conclusions: Rectal symptoms and fecal incontinence after conformal radiation therapy for prostate cancer are mostly intermittent. Fecal incontinence, fecal urge and tenesmus are associated with lower global quality of life levels

Outcomes in men with large prostates ({>=}60 cm{sup 3}) treated with definitive proton therapy for prostate cancer

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Mcgee, Lisa; Mendenhall, William M. [Dept. of Radiation Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Mendenhall, Nancy P.; Morris, Christopher G.; Marcus, Robert J. Jr. [Dept. of Radiation Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Univ. of Florida Proton Therapy Inst., Jacksonville (United States); Henderson, Randal H.; Nichols, Romaine C. Jr.; Li, Zuofeng; Williams, Christopher R.; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: bhoppe@floridaproton.org

2013-04-15

Background: Large prostate size is associated with higher rates of genitourinary and gastrointestinal toxicities after definitive treatment for prostate cancer, and because of this many men will undergo cytoreduction with androgen deprivation therapy (ADT) before definitive therapy, which results in its own unique toxicities and worsens quality of life. This series investigates genitourinary and gastrointestinal toxicity in men with large prostates (> 60 cm{sup 3}) undergoing definitive proton therapy (PT) for prostate cancer. Material and methods: From 2006 to 2010, 186 men with prostates {>=}60 cm{sup 3} were treated with definitive PT (median dose, 78 CGE) for low- (47%), intermediate- (37%) and high-risk (16%) prostate cancer. Median prostate size was 76 cm{sup 3} (range, 60-143 cm{sup 3}) and pretreatment IPSS was > 15 in 27%. At baseline, 51% were managed for obstructive symptoms with transurethral resection of the prostate (TURP) (9.7%) or medical management with {alpha} blockers (32%), 5 {alpha}-reductase inhibitors (15%), and/or saw palmetto (11%). Fourteen men received ADT for cytoreduction. Results: Median follow-up was two years. Grade 3 genitourinary toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). Multivariate analysis demonstrated pretreatment medical management (p = 0.0065) and pretreatment TURP (p 0.0002) were significantly associated with grade 3 genitourinary toxicity. One man experienced grade 3 gastrointestinal toxicity and 15 men had grade 2 gastrointestinal toxicities. On multivariate analysis, dose > 78 CGE was associated with increased grade 2 + gastrointestinal toxicity (p = 0.0142). Conclusion: Definitive management of men with large prostates without ADT was associated with low rates of genitourinary and gastrointestinal toxicity.

Outcomes in men with large prostates (≥60 cm3) treated with definitive proton therapy for prostate cancer

International Nuclear Information System (INIS)

Mcgee, Lisa; Mendenhall, William M.; Mendenhall, Nancy P.; Morris, Christopher G.; Marcus, Robert J. Jr.; Henderson, Randal H.; Nichols, Romaine C. Jr.; Li, Zuofeng; Williams, Christopher R.; Hoppe, Bradford S.

2013-01-01

Background: Large prostate size is associated with higher rates of genitourinary and gastrointestinal toxicities after definitive treatment for prostate cancer, and because of this many men will undergo cytoreduction with androgen deprivation therapy (ADT) before definitive therapy, which results in its own unique toxicities and worsens quality of life. This series investigates genitourinary and gastrointestinal toxicity in men with large prostates (> 60 cm 3 ) undergoing definitive proton therapy (PT) for prostate cancer. Material and methods: From 2006 to 2010, 186 men with prostates ≥60 cm 3 were treated with definitive PT (median dose, 78 CGE) for low- (47%), intermediate- (37%) and high-risk (16%) prostate cancer. Median prostate size was 76 cm 3 (range, 60-143 cm 3 ) and pretreatment IPSS was > 15 in 27%. At baseline, 51% were managed for obstructive symptoms with transurethral resection of the prostate (TURP) (9.7%) or medical management with α blockers (32%), 5 α-reductase inhibitors (15%), and/or saw palmetto (11%). Fourteen men received ADT for cytoreduction. Results: Median follow-up was two years. Grade 3 genitourinary toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). Multivariate analysis demonstrated pretreatment medical management (p = 0.0065) and pretreatment TURP (p 0.0002) were significantly associated with grade 3 genitourinary toxicity. One man experienced grade 3 gastrointestinal toxicity and 15 men had grade 2 gastrointestinal toxicities. On multivariate analysis, dose > 78 CGE was associated with increased grade 2 + gastrointestinal toxicity (p = 0.0142). Conclusion: Definitive management of men with large prostates without ADT was associated with low rates of genitourinary and gastrointestinal toxicity

Probiotics for Rectal Volume Variation During Radiation Therapy for Prostate Cancer

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Ki, Yongkan [Department of Radiation Oncology, Pusan National University School of Medicine, Busan (Korea, Republic of); Kim, Wontaek, E-mail: rokwt@hanmail.net [Department of Radiation Oncology, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Jiho; Kim, Donghyun; Lee, Juhye; Park, Dahl; Jeon, Hosang [Department of Radiation Oncology, Pusan National University School of Medicine, Busan (Korea, Republic of); Ha, Honggu; Kim, Taenam [Department of Urology, Medical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Kim, Dongwon [Department of Radiation Oncology, Pusan National University School of Medicine, Busan (Korea, Republic of)

2013-11-15

Purpose: To investigate the effect of the probiotic Lactobacillus acidophilus on the percentage volume change of the rectum (PVC{sub R}), a crucial factor of prostate movement. Methods and Materials: Prostate cancer patients managed with tomotherapy as a radical treatment were enrolled in the study to take a probiotic capsule containing 1.0 × 10{sup 8} colony-forming units of L acidophilus or a placebo capsule twice daily. Radiation therapy was performed at a dose of 78 Gy in 39 fractions. The PVC{sub R}, defined as the difference in rectal volume between the planning computed tomographic (CT) and daily megavoltage CT images, was analyzed. Results: Forty patients were randomized into 2 groups. The L acidophilus group showed significantly lower median rectal volume and median PVC{sub R} values than the placebo group. L acidophilus showed a significant reduction effect on the PVC{sub R} (P<.001). However, the radiation therapy fraction number did not significantly influence the PVC{sub R}. Conclusions: L acidophilus was useful in reducing the PVC{sub R}, which is the most important determining factor of prostate position, during radiation therapy for prostate cancer.

Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

International Nuclear Information System (INIS)

Beyer, David C.; McKeough, Timothy; Thomas, Theresa

2005-01-01

Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] 70 years (p = 0.0013), Gleason score ≥ 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers

Risk of Second Cancers According to Radiation Therapy Technique and Modality in Prostate Cancer Survivors

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Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Wong, Jeannette; Kleinerman, Ruth; Kim, Clara; Morton, Lindsay [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bekelman, Justin E. [Department of Radiation Oncology, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2015-02-01

Purpose: Radiation therapy (RT) techniques for prostate cancer are evolving rapidly, but the impact of these changes on risk of second cancers, which are an uncommon but serious consequence of RT, are uncertain. We conducted a comprehensive assessment of risks of second cancer according to RT technique (>10 MV vs ≤10 MV and 3-dimensional [3D] vs 2D RT) and modality (external beam RT, brachytherapy, and combined modes) in a large cohort of prostate cancer patients. Methods and Materials: The cohort was constructed using the Surveillance Epidemiology and End Results-Medicare database. We included cases of prostate cancer diagnosed in patients 66 to 84 years of age from 1992 to 2004 and followed through 2009. We used Poisson regression analysis to compare rates of second cancer across RT groups with adjustment for age, follow-up, chemotherapy, hormone therapy, and comorbidities. Analyses of second solid cancers were based on the number of 5-year survivors (n=38,733), and analyses of leukemia were based on number of 2-year survivors (n=52,515) to account for the minimum latency period for radiation-related cancer. Results: During an average of 4.4 years' follow-up among 5-year prostate cancer survivors (2DRT = 5.5 years; 3DRT = 3.9 years; and brachytherapy = 2.7 years), 2933 second solid cancers were diagnosed. There were no significant differences in second solid cancer rates overall between 3DRT and 2DRT patients (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.91-1.09), but second rectal cancer rates were significantly lower after 3DRT (RR = 0.59, 95% CI: 0.40-0.88). Rates of second solid cancers for higher- and lower-energy RT were similar overall (RR = 0.97, 95% CI: 0.89-1.06), as were rates for site-specific cancers. There were significant reductions in colon cancer and leukemia rates in the first decade after brachytherapy compared to those after external beam RT. Conclusions: Advanced treatment planning may have reduced rectal

Hormonal therapy with external radiation therapy for metastatic spinal cord compression from newly diagnosed prostate cancer

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Kato, So; Hozumi, Takahiro; Yamakawa, Kiyofumi; Higashikawa, Akiro; Goto, Takahiro; Shinohara, Mitsuru; Kondo, Taiji

2013-01-01

Although hormonal therapy is effective for treatment of prostate cancer, its effect in the treatment of metastatic spinal cord compression (MSCC) has not been established. The objective of this study was to clarify the efficacy of conservative treatment of MSCC-induced paralysis resulting from prostate cancer for patients without a previous treatment history. We reviewed data from 38 patients with MSCC-induced paralysis from newly diagnosed prostate cancer who presented to our service between 1984 and 2010. Conservative treatment consisted of hormonal therapy with external radiation therapy (ERT). Patient demographic data, treatment details, involved spine MRI images, complications, and the course of neurologic recovery were investigated. Twenty-five patients were treated conservatively. Mean follow-up period was 36.8 months. Sixteen patients (two with Frankel B, 14 with Frankel C) were unable to walk at initial presentation. After initiating conservative treatment, 75% (12 of 16) of these patients regained the ability to walk within 1 month, 88% (14 in 16) did so within 3 months, and all non-ambulatory patients did so within 6 months. No one had morbid complications. Four patients who did not regain the ability to walk at 1 month were found to have progressed to paraplegia rapidly, and tended to have severe compression as visualized on MRI, with a delay in the start of treatment in comparison with those who did so within 1 month (21.0 vs. 7.8 days). Hormonal therapy associated with ERT is an important option for treatment of MSCC resulting from newly diagnosed prostate cancer. (author)

Proton therapy for prostate cancer online: patient education or marketing?

Science.gov (United States)

Sadowski, Daniel J; Ellimoottil, Chandy S; Tejwani, Ajay; Gorbonos, Alex

2013-12-01

Proton therapy (PT) for prostate cancer is an expensive treatment with limited evidence of benefit over conventional radiotherapy. We sought to study whether online information on PT for prostate cancer was balanced and whether the website source influenced the content presented. We applied a systematic search process to identify 270 weblinks associated with PT for prostate cancer, categorized the websites by source, and filtered the results to 50 websites using predetermined criteria. We then used a customized version of the DISCERN instrument, a validated tool for assessing the quality of consumer health information, to evaluate the remaining websites for balance of content and description of risks, benefits and uncertainty. Depending on the search engine and key word used, proton center websites (PCWs) made up 10%-47% of the first 30 encountered links. In comparison, websites from academic and nonacademic medical centers without ownership stake in proton centers appeared much less frequently as a search result (0%-3%). PCWs scored lower on DISCERN questions compared to other sources for being balanced/unbiased (p online information regarding PT for prostate cancer may represent marketing by proton centers rather than comprehensive and unbiased patient education. An awareness of these results will also better prepare clinicians to address the potential biases of patients with prostate cancer who search the Internet for health information.

3D conformal radiation therapy and hormonal therapy for localized prostate cancer: Is age a limiting factor?

International Nuclear Information System (INIS)

Faure, A.; Negrea, T.; Lechevallier, E.; Coulange, C.; Murraciole, X.; Jouvea, E.; Sambuca, R.; Cowen, D.

2011-01-01

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9 300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71 92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67 80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P ≡ ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients. (authors)

Probiotics for Rectal Volume Variation During Radiation Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Ki, Yongkan; Kim, Wontaek; Nam, Jiho; Kim, Donghyun; Lee, Juhye; Park, Dahl; Jeon, Hosang; Ha, Honggu; Kim, Taenam; Kim, Dongwon

2013-01-01

Purpose: To investigate the effect of the probiotic Lactobacillus acidophilus on the percentage volume change of the rectum (PVC R ), a crucial factor of prostate movement. Methods and Materials: Prostate cancer patients managed with tomotherapy as a radical treatment were enrolled in the study to take a probiotic capsule containing 1.0 × 10 8 colony-forming units of L acidophilus or a placebo capsule twice daily. Radiation therapy was performed at a dose of 78 Gy in 39 fractions. The PVC R , defined as the difference in rectal volume between the planning computed tomographic (CT) and daily megavoltage CT images, was analyzed. Results: Forty patients were randomized into 2 groups. The L acidophilus group showed significantly lower median rectal volume and median PVC R values than the placebo group. L acidophilus showed a significant reduction effect on the PVC R (P R . Conclusions: L acidophilus was useful in reducing the PVC R , which is the most important determining factor of prostate position, during radiation therapy for prostate cancer

Self-assembled albumin nanoparticles for combination therapy in prostate cancer

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Lian H

2017-10-01

Full Text Available Huibo Lian,1 Jinhui Wu,2 Yiqiao Hu,2 Hongqian Guo1 1Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, 2State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China Abstract: Resistance to regular treatment strategies is a big challenge in the treatment of castration-resistant prostate cancer. Combination of photothermal and photodynamic therapy (PTT/PDT with chemotherapy offers unique advantages over monotherapy alone. However, free drugs, such as photosensitizers and chemotherapeutic agents, lack tumor-targeted accumulation and can be easily eliminated from the body. Moreover, most of the PTT drugs are hydrophobic and their organic solvents have in vivo toxicity, thereby limiting their potential in clinical translation. Herein, simple multifunctional nanoparticles (NPs using IR780 (a near-infrared dye and docetaxel (DTX-loaded nanoplatform based on human serum albumin (HSA (HSA@IR780@DTX was developed for targeted imaging and for PTT/PDT with chemotherapy for the treatment of castration-resistant prostate cancer treatment. In this platform, HSA is a biocompatible nanocarrier that binds to both DTX and IR780. DTX and IR780, as hydrophobic drug, can induce the self-assembly of HSA proteins. Transmission electron microscopic imaging showed that NPs formed by self-assembly are spherical with a smooth surface with a hydrodynamic diameter of 146.5±10.8 nm. The cytotoxicity of HSA@IR780@DTX NPs with or without laser irradiation in prostate cancer cells (22RV1 was determined via CCK-8 assay. The antitumor effect of HSA@IR780@DTX plus laser irradiation was better than either HSA@IR780@DTX without laser exposure or single PTT heating induced by HSA@IR780 NPs under near-infrared laser, suggesting a significant combined effect in comparison to monotherapy. Near-infrared fluorescence imaging showed that HSA@IR780@DTX NPs could preferentially

Depression related to (neo)adjuvant hormonal therapy for prostate cancer

International Nuclear Information System (INIS)

Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

2011-01-01

Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

PREVENTION OF DYSURIA AFTER HIFU THERAPY FOR PROSTATE CANCER

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A. Yu. Shestaev

2014-01-01

Full Text Available Objective: to identify factors for the development of dysuria and its prevention in patients with prostate cancer (PC after high-intensity focused ultrasound (HIFU therapy.Subjects and methods. In September 2008 to June 2013, the Clinic of Urology, S.M. Kirov Military Medical Academy, treated 98 patients, by performing HIFU sessions on an Ablatherm apparatus (EDAP, France. All the patients underwent transurethral resection of the prostate (TURP to reduce the volume of the ablated tissue. The patients were divided into 2 groups: 1 29 patients underwent TURP 3 days before HIFU therapy; 2 69 did this 1 month before major surgery. Each group was divided into 2 subgroups: 1 after ultrasound ablation, a urethral catheter was inserted for 10 days; 2 epicystostoma was applied, followed by its overlapping on day 3 postablation and spontaneous urination. The postoperative incidence of dysuria was estimated from subjective (complaints, voiding diary, and Inter-national Prostate Symptom Score and objective (uroflowmetry, small pelvic ultrasonography with determination of residual urine volume criteria.Results. In the patients who had undergone TURP one month before HIFU therapy, grades I–II urinary incontinence and urethral pros-tatic stricture occurred much less infrequently than in those who had undergone this maneuver 3 days prior to major surgery. Urinary in-continence and urethral prostatic stricture occurred 2-fold more frequently after TURP being carried out 3 days before HIFU therapy than after the urethral catheter being inserted. TURP performed one month before HIFU therapy showed no great difference in the incidence complications regardless of the type of bladder drainage.Conclusion. The short interval between TURP and HIFU therapy for PC increases the risk of postoperative dysuric events. The optimal time to perform TURP prior to HIFU therapy is 1 month.

PREVENTION OF DYSURIA AFTER HIFU THERAPY FOR PROSTATE CANCER

Directory of Open Access Journals (Sweden)

A. Yu. Shestaev

2014-07-01

Full Text Available Objective: to identify factors for the development of dysuria and its prevention in patients with prostate cancer (PC after high-intensity focused ultrasound (HIFU therapy.Subjects and methods. In September 2008 to June 2013, the Clinic of Urology, S.M. Kirov Military Medical Academy, treated 98 patients, by performing HIFU sessions on an Ablatherm apparatus (EDAP, France. All the patients underwent transurethral resection of the prostate (TURP to reduce the volume of the ablated tissue. The patients were divided into 2 groups: 1 29 patients underwent TURP 3 days before HIFU therapy; 2 69 did this 1 month before major surgery. Each group was divided into 2 subgroups: 1 after ultrasound ablation, a urethral catheter was inserted for 10 days; 2 epicystostoma was applied, followed by its overlapping on day 3 postablation and spontaneous urination. The postoperative incidence of dysuria was estimated from subjective (complaints, voiding diary, and Inter-national Prostate Symptom Score and objective (uroflowmetry, small pelvic ultrasonography with determination of residual urine volume criteria.Results. In the patients who had undergone TURP one month before HIFU therapy, grades I–II urinary incontinence and urethral pros-tatic stricture occurred much less infrequently than in those who had undergone this maneuver 3 days prior to major surgery. Urinary in-continence and urethral prostatic stricture occurred 2-fold more frequently after TURP being carried out 3 days before HIFU therapy than after the urethral catheter being inserted. TURP performed one month before HIFU therapy showed no great difference in the incidence complications regardless of the type of bladder drainage.Conclusion. The short interval between TURP and HIFU therapy for PC increases the risk of postoperative dysuric events. The optimal time to perform TURP prior to HIFU therapy is 1 month.

Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

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Fuminori Sato

2005-09-01

Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

Prostate cancer volume adds significantly to prostate-specific antigen in the prediction of early biochemical failure after external beam radiation therapy

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Propert, Kathleen J.

1996-01-01

Purpose: A new clinical pretreatment quantity that closely approximates the true prostate cancer volume is defined. Methods and Materials: The cancer-specific prostate-specific antigen (PSA), PSA density, prostate cancer volume (V Ca ), and the volume fraction of the gland involved with carcinoma (V Ca fx) were calculated for 227 prostate cancer patients managed definitively with external beam radiation therapy. 1. PSA density PSA/ultrasound prostate gland volume 2. Cancer-specific PSA = PSA - [PSA from benign epithelial tissue] 3. V Ca = Cancer-specific PSA/[PSA in serum per cm 3 of cancer] 4. V Ca fx = V Ca /ultrasound prostate gland volume A Cox multiple regression analysis was used to test whether any of these-clinical pretreatment parameters added significantly to PSA in predicting early postradiation PSA failure. Results: The prostate cancer volume (p = 0.039) and the volume fraction of the gland involved by carcinoma (p = 0.035) significantly added to the PSA in predicting postradiation PSA failure. Conversely, the PSA density and the cancer-specific PSA did not add significantly (p > 0.05) to PSA in predicting postradiation PSA failure. The 20-month actuarial PSA failure-free rates for patients with calculated tumor volumes of ≤0.5 cm 3 , 0.5-4.0 cm 3 , and >4.0 cm 3 were 92, 80, and 47%, respectively (p = 0.00004). Conclusion: The volume of prostate cancer (V Ca ) and the resulting volume fraction of cancer both added significantly to PSA in their ability to predict for early postradiation PSA failure. These new parameters may be used to select patients in prospective randomized trials that examine the efficacy of combining radiation and androgen ablative therapy in patients with clinically localized disease, who are at high risk for early postradiation PSA failure

[New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer].

Science.gov (United States)

Vlasova, O P; German, K E; Krilov, V V; Petriev, V M; Epstein, N B

2015-01-01

About 10.7% cases of prostate cancer were registered in Russia in 2011 (40,000 patients). More than half of cancer cases were revealed in advanced (III-IV) stages when metastases inevitably developed quickly. Clinical problem of early diagnostics and treatment of metastatic prostate cancer is still not solved. Anatomical imaging techniques have low sensitivity and specificity for the detection of this disease. Metabolic visualization methods which use prostate specific antigen (PSA) as a marker are also ineffective. This article describes prostate-specific membrane antigens (PSMA) that are proposed as a marker for diagnostics and therapy of prostate cancer. The most promising PSMA-based radiopharmaceutical agent for diagnostics has been developed and clinically tested in the European countries. These pharmaceuticals are based on small peptide molecules modified with urea, and have the highest affinity to PSMA. Favorable phannacokinetics, rapid accumulation in the tumor and rapid excretion from the body are beneficial features of these pharmaceuticals.

Immunotherapy and Immune Evasion in Prostate Cancer

International Nuclear Information System (INIS)

Thakur, Archana; Vaishampayan, Ulka; Lum, Lawrence G.

2013-01-01

Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

Immunotherapy and Immune Evasion in Prostate Cancer

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Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

2013-05-24

Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

Science.gov (United States)

Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

2011-06-01

• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

International Nuclear Information System (INIS)

Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

2011-01-01

Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm 3 , respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm 3 ) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm 3 increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer

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Muldermans, Jonathan L. [F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Romak, Lindsay B. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Kwon, Eugene D. [Department of Urology, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Park, Sean S. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Olivier, Kenneth R., E-mail: olivier.kenneth@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

2016-06-01

Purpose: To review outcomes of patients with oligometastatic prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT) and to identify variables associated with local failure. Methods and Materials: We retrospectively reviewed records of patients treated with SBRT for oligometastatic PCa. Metastasis control (ie, control of the treated lesion, MC), biochemical progression-free survival, distant progression-free survival, and overall survival were estimated with the Kaplan-Meier method. Results: Sixty-six men with 81 metastatic PCa lesions, 50 of which were castrate-resistant, were included in the analysis. Lesions were in bone (n=74), lymph nodes (n=6), or liver (n=1). Stereotactic body radiation therapy was delivered in 1 fraction to 71 lesions (88%), at a median dose of 16 Gy (range, 16-24 Gy). The remaining lesions received 30 Gy in 3 fractions (n=6) or 50 Gy in 5 fractions (n=4). Median follow-up was 16 months (range, 3-49 months). Estimated MC at 2 years was 82%. Biochemical progression-free survival, distant progression-free survival, and overall survival were 54%, 45%, and 83%, respectively. On multivariate analysis, only the dose of SBRT was significantly associated with MC; lesions treated with 16 Gy had 58% MC, and those treated with ≥18 Gy had 95% MC at 2 years (P≤.001). At 2 years, MC for lesions treated with 18 Gy (n=21) was 88%. No patient treated with ≥18 Gy in a single fraction or with any multifraction regimen had local failure. Six patients (9%) had grade 1 pain flare, and 2 (3%) had grade 2 pain flare. No grade 2 or greater late toxicities were reported. Conclusions: Stereotactic body radiation therapy for patients with oligometastatic prostate cancer provided optimal metastasis control and acceptable toxicity with doses ≥18 Gy. Biochemical progression-free survival was 54% at 16 months with the inclusion of SBRT in the treatment regimen. Stereotactic body radiation therapy should be considered in

Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer

International Nuclear Information System (INIS)

Muldermans, Jonathan L.; Romak, Lindsay B.; Kwon, Eugene D.; Park, Sean S.; Olivier, Kenneth R.

2016-01-01

Purpose: To review outcomes of patients with oligometastatic prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT) and to identify variables associated with local failure. Methods and Materials: We retrospectively reviewed records of patients treated with SBRT for oligometastatic PCa. Metastasis control (ie, control of the treated lesion, MC), biochemical progression-free survival, distant progression-free survival, and overall survival were estimated with the Kaplan-Meier method. Results: Sixty-six men with 81 metastatic PCa lesions, 50 of which were castrate-resistant, were included in the analysis. Lesions were in bone (n=74), lymph nodes (n=6), or liver (n=1). Stereotactic body radiation therapy was delivered in 1 fraction to 71 lesions (88%), at a median dose of 16 Gy (range, 16-24 Gy). The remaining lesions received 30 Gy in 3 fractions (n=6) or 50 Gy in 5 fractions (n=4). Median follow-up was 16 months (range, 3-49 months). Estimated MC at 2 years was 82%. Biochemical progression-free survival, distant progression-free survival, and overall survival were 54%, 45%, and 83%, respectively. On multivariate analysis, only the dose of SBRT was significantly associated with MC; lesions treated with 16 Gy had 58% MC, and those treated with ≥18 Gy had 95% MC at 2 years (P≤.001). At 2 years, MC for lesions treated with 18 Gy (n=21) was 88%. No patient treated with ≥18 Gy in a single fraction or with any multifraction regimen had local failure. Six patients (9%) had grade 1 pain flare, and 2 (3%) had grade 2 pain flare. No grade 2 or greater late toxicities were reported. Conclusions: Stereotactic body radiation therapy for patients with oligometastatic prostate cancer provided optimal metastasis control and acceptable toxicity with doses ≥18 Gy. Biochemical progression-free survival was 54% at 16 months with the inclusion of SBRT in the treatment regimen. Stereotactic body radiation therapy should be considered in

Immunotherapy in metastatic prostate cancer

Directory of Open Access Journals (Sweden)

Susan F Slovin

2016-01-01

Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

A pilot study of exercise in men with prostate cancer receiving androgen deprivation therapy

International Nuclear Information System (INIS)

Lee, C Ellen; Leslie, William D; Lau, YK James

2012-01-01

Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT. A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data. Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

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See, William A; Wirth, Manfred P; McLeod, David G

2002-01-01

We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.......We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer....

The Danish Prostate Cancer Database

DEFF Research Database (Denmark)

Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren

2016-01-01

variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). DESCRIPTIVE DATA: In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015......AIM OF DATABASE: The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer...... care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. STUDY POPULATION: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. MAIN VARIABLES: The DAPROCAdata...

The link between benign prostatic hyperplasia and prostate cancer

DEFF Research Database (Denmark)

Ørsted, David Dynnes; Bojesen, Stig E

2013-01-01

Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen...... therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological...... studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH...

Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score

Science.gov (United States)

Akaza, Hideyuki; Hinotsu, Shiro; Usami, Michiyuki; Ogawa, Osamu; Kitamura, Tadaichi; Suzuki, Kazuhiro; Tsukamoto, Taiji; Naito, Seiji; Namiki, Mikio; Hirao, Yoshihiko; Murai, Masaru

2013-01-01

Purpose: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. Methods: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. Results: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. Conclusions: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients. PMID:24223407

Eph receptor A10 has a potential as a target for a prostate cancer therapy

International Nuclear Information System (INIS)

Nagano, Kazuya; Yamashita, Takuya; Inoue, Masaki; Higashisaka, Kazuma; Yoshioka, Yasuo; Abe, Yasuhiro; Mukai, Yohei; Kamada, Haruhiko

2014-01-01

Highlights: • EphA10 mRNA is overexpressed in breast, prostate and colon cancer cell lines. • EphA10 is overexpressed in clinical prostate tumors at mRNA and protein levels. • Anti-EphA10 antibodies were cytotoxic on EphA10-positive prostate cancer cells. - Abstract: We recently identified Eph receptor A10 (EphA10) as a novel breast cancer-specific protein. Moreover, we also showed that an in-house developed anti-EphA10 monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer cells, suggesting EphA10 as a promising target for breast cancer therapy. However, the only other known report for EphA10 was its expression in the testis at the mRNA level. Therefore, the potency of EphA10 as a drug target against cancers other than the breast is not known. The expression of EphA10 in a wide variety of cancer cells was studied and the potential of EphA10 as a drug target was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was overexpressed in breast cancer cell lines as well as in prostate and colon cancer cell lines. Thus, we focused on prostate cancers in which EphA10 expression was equivalent to that in breast cancers. As a result, EphA10 expression was clearly shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and protein levels. In order to evaluate the potential of EphA10 as a drug target, we analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found that significant cytotoxicity was mediated by the expression of EphA10. Therefore, the idea was conceived that the overexpression of EphA10 in prostate cancers might have a potential as a target for prostate cancer therapy, and formed the basis for the studies reported here

uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

DEFF Research Database (Denmark)

Persson, Morten; Juhl, Karina; Rasmussen, Palle

2014-01-01

The urokinase-type plasminogen activator receptor (uPAR) is implicated in cancer invasion and metastatic development in prostate cancer and provides therefore an attractive molecular target for both imaging and therapy. In this study, we provide the first in vivo data on an antimetastatic effect...... of uPAR radionuclide targeted therapy in such lesions and show the potential of uPAR positron emission tomography (PET) imaging for identifying small foci of metastatic cells in a mouse model of disseminating human prostate cancer. Two radiolabeled ligands were generated in high purity and specific...... value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p

Autophagosomal Sequestration of Mitochondria as an Indicator of Antiandrogen Therapy Resistance of Prostate Cancer (PCa)

Science.gov (United States)

2017-11-01

Prostate Cancer (PCa) PRINCIPAL INVESTIGATOR: George Wilding, M.D. CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer Center Houston, TX...Indicator of Antiandrogen Therapy Resistance of Prostate Cancer (PCa) 5b. GRANT NUMBER W81XWH-15-1-0509 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER The University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd. Houston, TX 77030-4009

Role of transurethral resection of the prostate in the management of prostate cancer

Directory of Open Access Journals (Sweden)

Szollosi Attila

2016-06-01

Full Text Available Introduction: Prostate cancer is the second most diagnosed cancer in men, after lung cancer. The gold standard procedure in prostate cancer (PCa diagnosis is the ultrasound guided prostate biopsy. Transurethral resection of the prostate (TURP used in solving the bladder outlet obstruction, can have a role in detection of PCa. The aim of this retrospective study is to examine the role of transurethral resection of the prostate in the diagnosis and therapy of prostate cancer.

Hematuria following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer

International Nuclear Information System (INIS)

Gurka, Marie K; Chen, Leonard N; Bhagat, Aditi; Moures, Rudy; Kim, Joy S; Yung, Thomas; Lei, Siyuan; Collins, Brian T; Krishnan, Pranay; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P

2015-01-01

Hematuria following prostate radiotherapy is a known toxicity that may adversely affect a patient’s quality of life. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT hematuria would be more common than with alternative radiation therapy approaches. Herein, we describe the incidence and severity of hematuria following stereotactic body radiation therapy (SBRT) for prostate cancer at our institution. Two hundred and eight consecutive patients with prostate cancer treated with SBRT monotherapy with at least three years of follow-up were included in this retrospective analysis. Treatment was delivered using the CyberKnife® (Accuray) to doses of 35–36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.4. Hematuria was counted at the highest grade it occurred in the acute and late setting for each patient. Cystoscopy findings were retrospectively reviewed. Univariate and multivariate analyses were performed. Hematuria-associated bother was assessed via the Expanded Prostate Index Composite (EPIC)-26. The median age was 69 years with a median prostate volume of 39 cc. With a median follow-up of 48 months, 38 patients (18.3%) experienced at least one episode of hematuria. Median time to hematuria was 13.5 months. In the late period, there were three grade 3 events and five grade 2 events. There were no grade 4 or 5 events. The 3-year actuarial incidence of late hematuria ≥ grade 2 was 2.4%. On univariate analysis, prostate volume (p = 0.022) and history of prior procedure(s) for benign prostatic hypertrophy (BPH) (p = 0.002) were significantly associated with hematuria. On multivariate analysis, history of prior procedure(s) for BPH (p < 0.0001) and α 1A antagonist use (p = 0.008) were significantly associated with the development of hematuria. SBRT for prostate cancer was well tolerated with hematuria rates comparable to other radiation modalities. Patients factors

[Epigenetics of prostate cancer].

Science.gov (United States)

Yi, Xiao-Ming; Zhou, Wen-Quan

2010-07-01

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

A comparison of robotic arm versus gantry linear accelerator stereotactic body radiation therapy for prostate cancer.

Science.gov (United States)

Avkshtol, Vladimir; Dong, Yanqun; Hayes, Shelly B; Hallman, Mark A; Price, Robert A; Sobczak, Mark L; Horwitz, Eric M; Zaorsky, Nicholas G

2016-01-01

Prostate cancer is the most prevalent cancer diagnosed in men in the United States besides skin cancer. Stereotactic body radiation therapy (SBRT; 6-15 Gy per fraction, up to 45 minutes per fraction, delivered in five fractions or less, over the course of approximately 2 weeks) is emerging as a popular treatment option for prostate cancer. The American Society for Radiation Oncology now recognizes SBRT for select low- and intermediate-risk prostate cancer patients. SBRT grew from the notion that high doses of radiation typical of brachytherapy could be delivered noninvasively using modern external-beam radiation therapy planning and delivery methods. SBRT is most commonly delivered using either a traditional gantry-mounted linear accelerator or a robotic arm-mounted linear accelerator. In this systematic review article, we compare and contrast the current clinical evidence supporting a gantry vs robotic arm SBRT for prostate cancer. The data for SBRT show encouraging and comparable results in terms of freedom from biochemical failure (>90% for low and intermediate risk at 5-7 years) and acute and late toxicity (6 MV). Finally, SBRT (particularly on a gantry) may also be more cost-effective than conventionally fractionated external-beam radiation therapy. Randomized controlled trials of SBRT using both technologies are underway.

Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

International Nuclear Information System (INIS)

Kaidar-Person, Orit; Roach, Mack; Créhange, Gilles

2013-01-01

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer

Whole-Pelvic Nodal Radiation Therapy in the Context of Hypofractionation for High-Risk Prostate Cancer Patients: A Step Forward

Energy Technology Data Exchange (ETDEWEB)

Kaidar-Person, Orit [Division of Oncology, Rambam Health Care Campus, Haifa (Israel); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Créhange, Gilles, E-mail: gcrehange@cgfl.fr [Department of Radiation Oncology, Georges-François Leclerc Cancer Center, Dijon (France)

2013-07-15

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer.

Impact of Androgen Deprivation Therapy on Self-Reported Cognitive Function in Men with Prostate Cancer.

Science.gov (United States)

Marzouk, Shireen; Naglie, Gary; Tomlinson, George; Duff Canning, Sarah; Breunis, Henriette; Timilshina, Narhari; Alibhai, Shabbir M H

2018-03-01

Although androgen deprivation therapy is widely used to treat prostate cancer, its effects on cognitive function are unclear. To our knowledge no prior report has examined the impact of androgen deprivation therapy on self-reported cognitive function. Three groups of men 50 years old or older who were matched on age and education were enrolled in the study, including 81 with prostate cancer starting on continuous androgen deprivation therapy, 84 controls with prostate cancer not receiving androgen deprivation therapy and 85 healthy controls. Two scales from the FACT-Cog (Functional Assessment of Cancer Therapy-Cognitive subscale) version 3 were used to assess self-reported cognitive function. Changes in cognitive scores with time were analyzed by 2 approaches, including 1) multivariable regression and 2) calculation of the proportion of subjects per group with a decrease of 1 SD or more. Multivariable regression was applied to assess predictors of a decline in self-reported cognitive function. We also examined relationships between the FACT-Cog and a neuropsychological battery of 15 tests. Mean participant age was 69 years (range 50 to 87). The mean educational level was 15 years (range 8 to 24). FACT-Cog scores were similar at baseline across the cohorts. Neither analytical approach revealed that androgen deprivation therapy was associated with changes in self-reported cognitive function on either FACT-Cog scale. Mood and fatigue correlated with changes in self-reported cognitive function. The relationship between self-reported and objective cognitive measures was weak (maximum Spearman correlation coefficient 0.14) and only 2 of 30 correlations were statistically significant. A total of 12 months of androgen deprivation therapy were not associated with self-reported cognitive function changes in older men with nonmetastatic prostate cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

Prostate-specific antigen bounce following stereotactic body radiation therapy for prostate cancer

Directory of Open Access Journals (Sweden)

Charles C. Vu

2014-01-01

Full Text Available Introduction: Prostate-specific antigen (PSA bounce after brachytherapy has been well-documented. This phenomenon has also been identified in patients undergoing stereotactic body radiation therapy (SBRT. While the parameters that predict PSA bounce have been extensively studied in prostate brachytherapy patients, this study is the first to analyze the clinical and pathologic predictors of PSA bounce in prostate SBRT patients. Materials and Methods: Our institution has maintained a prospective database of patients undergoing SBRT for prostate cancer since 2006. Our study population includes patients between May 2006 and November 2011 who have at least 18 months of follow-up. All patients were treated using the CyberKnife treatment system. The prescription dose was 3500-3625cGy in 5 fractions.Results: 120 patients were included in our study. Median PSA follow-up was 24 months (range 18-78 months. 34 (28% patients had a PSA bounce. The median time to PSA bounce was 9 months, and the median bounce size was 0.50ng/mL. On univariate analysis, only younger age (p = .011 was shown to be associated with an increased incidence of PSA bounce. Other patient factors, including race, prostate size, prior treatment by hormones, and family history of prostate cancer, did not predict PSA bounces. None of the tumor characteristics studied, including Gleason score, pre-treatment PSA, T-stage, or risk classification by NCCN guidelines, was associated with increased incidence of PSA bounces. Younger age was the only statistically significant predictor of PSA bounce on multivariate analysis (OR = 0.937, p = 0.009.Conclusion: PSA bounce, which has been reported after prostate brachytherapy, is also seen in a significant percentage of patients after CyberKnife SBRT. Close observation rather than biopsy can be considered for these patients. Younger age was the only factor that predicted PSA bounce.

Mesenchymal Stem Cell Based Therapy for Prostate Cancer

Science.gov (United States)

2015-11-01

Montero-Menei, C.; Menei, P. Mesenchymal Stem Cells as Cellular Vehicles for Delivery of Nanoparticles to Brain Tumors. Biomaterials 2010, 31, 8393... Stem Cells : Considerations for Regenerative Medicine Approaches. Tissue Eng. Part B. Rev. 2010, 16, 159–168. 55. Ellem, S. J.; Taylor, R. a.; Furic, L...Award Number: W81XWH-13-1-0304 TITLE: Mesenchymal Stem Cell -Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs CONTRACTING

Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

Science.gov (United States)

2017-10-01

of this study is to develop a strategy to identify molecular markers of response of advanced prostate cancer to specific therapies using clinically...combination treatment strategies are urgently needed. The purpose of this study is to develop a strategy for identifying molecular markers of response of...PENDING) Level of Funding: $125,978 annual direct Project Goals: To develop a strategy for identifying molecular therapeutic response markers of

Hip fractures and pain following proton therapy for management of prostate cancer

International Nuclear Information System (INIS)

Valery, Raul; Mendenhall, Nancy P.; Nichols, Romaine C. Jr.; Henderson, Randal; Morris, Christopher G.; Su, Zhong; Li, Zuofeng; Hoppe, Bradford S.; Mendenhall, William M.; Williams, Christopher R.

2013-01-01

Background: Proton therapy (PT) for prostate cancer reduces rectal and bladder dose, but increases dose to the femoral necks. We assessed the risk of hip fracture and pain in men treated with PT for prostate cancer. Material and methods: From 2006 to 2008, 382 men were treated for prostate cancer and evaluated at six-month intervals after PT for toxicities at Univ. of Florida Proton Therapy Institute (UFPTI). The WHO Fracture Risk Assessment Tool (FRAX) generated annual hip-fracture risk for the cohort. The WHO FRAX tool was utilized to generate the expected number of patients with hip fractures and the observed-to-expected ratio; confidence intervals and p-value were generated with the mid-P exact test. Univariate analysis of hip pain as a function of several prognostic factors was accomplished with Fisher's exact test. Results. Median follow-up was four years (range, 0.1-5.5 years). Per FRAX, 3.02 patients were expected to develop a hip fracture without PT. Three PT patients actually developed fractures for a rate of 0.21 fractures per 100 person-years of follow-up. There was an observed-expected ratio of 0.99 (p-value not significant). Forty-eight patients (13%) reported new pain in the hip during follow-up; three required prescription analgesics. Conclusion. PT for prostate cancer did not increase hip-fractures in the first four years after PT compared to expected rates in untreated men

Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

DEFF Research Database (Denmark)

Kongsted, Per; Svane, Inge M; Lindberg, Henriette

2016-01-01

To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

Long term results in radiotherapy of prostatic cancer

International Nuclear Information System (INIS)

Bagshaw, M.A.; Ray, G.R.; Cox, R.S.

1987-01-01

Discounting skin cancer, prostatic cancer remains second only to lung cancer in incidence in the United States. Colon Cancer is a close third. The incidence of lung cancer has started to decline slightly in the male, while prostatic cancer continues to increase, no doubt related to the aging of the population. Radiation therapy was first used in the treatment of prostatic cancer in the United States about 1915, having been introduced as intracavitary radium treatments by the American urologist, Hugh Young. External beam irradiation was used in the 1930's, but mostly for palliation of ureteral and vascular obstruction. Definitive use was first described by other investigators in the 1940's' however, attention changed to hormonal manipulation following Huggin's discovery of the dependency of prostate cancer on male hormone. Improved radiation therapy sources were invented, such as Cobalt 60 units, linear accelerators and betatrons, stimulated a reinvestigation of the definitive use of radiation therapy to prostate cancer in the 1950's. According to the current American College of Surgeon's survey of patterns of care of patients with prostate cancer, the use of external beam irradiation for the treatment of prostatic cancer has doubled in the United States during the past decade; however, apparently in Europe, hormone deprivation remains the therapeutic standard

Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.

Science.gov (United States)

Steer, Anna N; Aherne, Noel J; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P

2013-07-15

Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Steer, Anna N.; Aherne, Noel J.; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P.

2013-01-01

Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery

Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Steer, Anna N. [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Aherne, Noel J., E-mail: noel.aherne@ncahs.health.nsw.gov.au [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Rural Clinical School Faculty of Medicine, University of New South Wales, Coffs Harbour (Australia); Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Shakespeare, Thomas P. [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Rural Clinical School Faculty of Medicine, University of New South Wales, Coffs Harbour (Australia)

2013-07-15

Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

Mitochondrial mutations drive prostate cancer aggression

DEFF Research Database (Denmark)

Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

2017-01-01

Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy

Directory of Open Access Journals (Sweden)

Mankgopo M. Kgatle

2016-01-01

Full Text Available Prostate cancer (PCa is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

Science.gov (United States)

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Prognostic significance of obstructive uropathy in advanced prostate cancer.

Science.gov (United States)

Oefelein, Michael G

2004-06-01

To report the incidence and prognostic implications of obstructive uropathy (OU) in patients with advanced prostate cancer receiving androgen deprivation therapy and to define the impact initial local therapy has on the development of OU in patients with prostate cancer who develop recurrence and begin androgen deprivation therapy. From a population of 260 patients with advanced prostate cancer diagnosed between 1986 and 2003, OU was identified in 51 patients. The OU treatment options included ureteral stent, percutaneous nephrostomy, transurethral resection of the prostate, Foley catheter placement, and urinary diversion. Overall survival and the factors that influenced survival were calculated using standard statistical methods. OU was diagnosed in 15 (16%) of 80 patients who received local therapy with curative intent and in whom local therapy subsequently failed and in 36 (19%) of 180 patients who had never received local therapy (P = 0.7, chi-square test). Of these 51 patients, 39 had bladder neck obstruction and 16 had ureteral obstruction. Overall survival was significantly worse for the men with OU compared with those without OU (41 versus 54 months). OU was associated with tumor stage and androgen-insensitive prostate cancer. OU results in significantly reduced survival in men with prostate cancer. In a select group of patients with prostate cancer with progression after local therapy (primarily radiotherapy), no statistically significant reduction in the development of OU was observed relative to patients matched for stage, grade, and pretreatment prostate-specific antigen level treated with androgen deprivation therapy alone. Aggressive advanced stage and hormone-insensitive disease are variables associated with OU.

Cost comparison of curative therapies for localized prostate cancer in Japan. A single-institution experience

International Nuclear Information System (INIS)

Satoh, Takefumi; Ishiyama, Hiromichi; Matsumoto, Kazumasa

2009-01-01

In addition to open surgery, curative therapies for prostate cancer now include endoscopic surgery and radiation therapies. Because of the expansion and subdivision of treatment methods for prostate cancer, the medical fee point schedule in Japan was revised in fiscal year 2006. We examined changes in medical income and expenditure after this revision of the medical fee system. We studied income and expenditure, after institution of the new medical fee schedule, for the five types of therapies for prostate cancer performed at our hospital: two surgical therapies (radical retropubic prostatectomy and laparoscopic prostatectomy) and three radiation therapies (three-dimensional conformal radiation therapy, 192 Ir high-dose-rate brachytherapy, and 125 I low-dose-rate brachytherapy). Low-dose-rate brachytherapy was found to be associated with a profit of 199 yen per patient. Laparoscopic prostatectomy, a highly advanced medical treatment that the fee revision changed from a partially insured to an insured procedure, yielded a profit of 75672 yen per patient. However, high-dose-rate brachytherapy was associated with a loss of 654016 yen per patient. Given the loss in hospital income per patient undergoing high-dose-rate brachytherapy, the medical fee point system for this procedure should be reassessed. (author)

Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer.

LENUS (Irish Health Repository)

D'Amico, Anthony V

2011-12-10

We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.

Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer

Science.gov (United States)

Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

2005-01-01

In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

Clinical survey of prostate cancer

International Nuclear Information System (INIS)

Takada, Tsuyoshi; Hatano, Koji; Satoh, Mototaka; Tsujimoto, Yuichi; Honda, Masahito; Matsumiya, Kiyomi; Fujioka, Hideki

2007-01-01

Treatment trends and outcomes for prostate cancer in our hospital were reported. A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with prostatic specific antigen (PSA) elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p=0.0226), D (p=0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p=0.0027). In stage D2 patients, chemo-endocrine therapy with etoposide (VP-16), adriamycin (ADM) and cisplatin (CDDP) refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p=0.0467, P=0.0381). Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively. (author)

Preclinical targeted alpha therapy for melanoma, leukaemia, breast, prostate and colorectal cancers

International Nuclear Information System (INIS)

Allen, B.J.; Rizvi, S.; Li, Y.; Tian, Z.; University of Wollongong, NSW; Ranson, M.

2000-01-01

Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micro-metastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 are produced by accelerator and generator respectively and are chelated to a cancer specific monoclonal antibody, peptide or protein to form the alpha-conjugates (AC) against melanoma, leukaemia, breast, prostate and colorectal cancers. These ACs are tested for stability, specificity and cytotoxicity in vitro and in vivo using several nude mouse models. The Australian TAT program began some 7 years at ANSTO but was still-born. Later, TAT had a second wind at St George Hospital, where collaborative research led to the investigation of Tb-149 as a new alpha emitting radionuclide. Subsequently, increased emphasis was placed on the Ac-225 generator to produce Bi-213. Although in-house funding was terminated in 1998, the project received its third wind with local fund raising in the Shire and a US grant in 1999, and continues to break new ground in the control of the above cancers. Stable alpha-ACs are produced which are highly specific and cytotoxic in vitro against melanoma, leukaemia, colorectal, breast and prostate cancers. Subcutaneous inoculation of 11.5 million cells into the flanks of nude mice causes tumours to grow in all mice. The tumour growth is compared with untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of melanoma xenografts and gives almost complete control of breast cancer tumour growth in the primary site and metastatic invasion of the lymph nodes. These results point to the application of local

Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

Science.gov (United States)

Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

1993-06-01

The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

Development of a Combination Therapy for Prostate Cancer by Targeting Stat3 and HIF-1alpha

Science.gov (United States)

2013-07-01

inflammation-induced cancer, making it an attractive target (25-27). A3. Innovation 1. TEL03 is a novel anti-cancer agent from Chinese herbal medicine ...agents from Chinese herbal medicine (CHM) that targets HIF-1α /2α for prostate cancer therapy. Hypoxia orchestrated by HIF-1αis crucial for tumor...Stat3 for treatment of prostate and other cancers. TEL03, which is a novel anti-cancer agent derived from Chinese herbal medicine (CHM: Hypocrella

Alpha Particle Therapy in Metastatic Prostate Cancer

International Nuclear Information System (INIS)

O’Sullivan, Joe

2013-01-01

Metastatic castrate resistant prostate cancer (CRPC) is a leading cause of cancer mortality among men in western countries. Although nearly 85% of patients present with localised disease, up to 40% will eventually develop metastatic disease during the course of illness. Of men dying from prostate cancer, more than 90% have bone metastases many with no other significant metastatic sites. Symptoms related to bone metastases and skeletal related events (SREs) account for the major cause of morbidity in these patients. Bone-seeking radionuclides have been used in the treatment of prostate cancer bone metastases for many years. The first bone seeking radionuclide drug approved by the FDA was Strontium-89. Other agents have also been used including Samarium-153 EDTMP, Rhenium-186 (-188)-HEDP. These radionuclides are all emit shortrange therapeutic beta radiation with bone marrow as the dose limiting toxicity. There is strong clinical trial evidence of benefit for these radionuclides in reducing pain in advanced prostate cancer; however, none of the drugs has been shown to improve survival, albeit none of the clinical trials were powered to detect differences in survival

Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter.

Science.gov (United States)

Ahn, M; Lee, S-J; Li, X; Jiménez, J A; Zhang, Y-P; Bae, K-H; Mohammadi, Y; Kao, C; Gardner, T A

2009-01-01

Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 microg ml(-1)), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy.

Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer

International Nuclear Information System (INIS)

Hurwitz, Mark D.; Kaur, Punit; Nagaraja, Ganachari M.; Bausero, Maria A.; Manola, Judith; Asea, Alexzander

2010-01-01

Background and purpose: Hsp72 found in the extracellular milieu has been shown to play an important role in immune regulation. The impact of common cancer therapies on extracellular release of Hsp72 however, has been to date undefined. Materials and methods: Serum from 13 patients undergoing radiation therapy (XRT) for prostate cancer with or without hormonal therapy (ADT) was measured for levels of circulating serum Hsp72 and pro-inflammatory cytokines (IL-6 and TNF-α) using the classical sandwich ELISA technique and the relative expression of CD8 + T lymphocytes and natural killer (NK) cells was measured using flow cytometry. Mouse orthotopic xenograft of human prostate cancer tumors (DU-145 and PC-3) were used to validate and further characterize the response noted in the clinical setting. The biological significance of tumor released Hsp72 was studied in human dendritic cells (DC) in vitro. Results: Circulating serum Hsp72 levels increased an average of 3.5-fold (median per patient 4.8-fold) with XRT but not with ADT (p = 0.0002). Increases in IL-6 (3.3-fold), TNF-α (1.8-fold), CD8 + CTL (2.1-fold) and NK cells (3.2-fold) also occurred. Using PC-3 and DU-145 human prostate cancer xenograft models in mice, we confirmed that XRT induces Hsp72 release primarily from implanted tumors. In vitro studies using supernatant recovered from irradiated human prostate cancer cells point to exosomes containing Hsp72 as a possible stimulator of pro-inflammatory cytokine production and costimulatory molecules expression in human DC. Conclusions: The current study confirms for the first time in an actual clinical setting elevation of circulating serum Hsp72 with XRT. The accompanying studies in mice and in vitro identify the released exosomes containing Hsp72 as playing a pivotal role in stimulating pro-inflammatory immune responses. These findings, if validated, may lead to new treatment paradigms for common human malignancies.

Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

International Nuclear Information System (INIS)

Solberg, Arne; Haugen, Olav A.; Viset, Trond; Bergh, Anders; Tasdemir, Ilker; Ahlgren, Goeran; Widmark, Anders; Angelsen, Anders

2011-01-01

Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66% (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score ≥8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.

Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

Directory of Open Access Journals (Sweden)

Pascoe Abigail C

2012-03-01

Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database

Directory of Open Access Journals (Sweden)

Anthony Ricco

2017-08-01

Full Text Available PurposeNo direct comparisons between extreme hypofractionation and conventional fractionation have been reported in randomized trials for the treatment of localized prostate cancer. The goal of this study is to use a propensity score matched (PSM analysis with the National Cancer Database (NCDB for the comparison of stereotactic body radiation therapy (SBRT and intensity modulated radiation therapy (IMRT for organ confined prostate cancer.MethodsMen with localized prostate cancer treated with radiation dose ≥72 Gy for IMRT and ≥35 Gy for SBRT to the prostate only were abstracted from the NCDB. Men treated with previous surgery, brachytherapy, or proton therapy were excluded. Matching was performed to eliminate confounding variables via PSM. Simple 1–1 nearest neighbor matching resulted in a matched sample of 5,430 (2,715 in each group. Subset analyses of men with prostate-specific antigen (PSA > 10, GS = 7, and GS > 7 yielded matched samples of 1,020, 2,194, and 247, respectively.ResultsNo difference in survival was noted between IMRT and SBRT at 8 years (p = 0.65. Subset analyses of higher risk men with PSA > 10 or GS = 7 histology or GS > 7 histology revealed no difference in survival between IMRT and SBRT (p = 0.58, p = 0.68, and p = 0.62, respectively. Variables significant for survival for the matched group included: age (p < 0.0001, primary payor (p = 0.0001, Charlson/Deyo Score (p = 0.0002, PSA (p = 0.0013, Gleason score (p < 0.0001, and use of hormone therapy (p = 0.02.ConclusionUtilizing the NCDB, there is no difference in survival at 8 years comparing IMRT to SBRT in the treatment of localized prostate cancer. Subset analysis confirmed no difference in survival even for intermediate- and high-risk patients based on Gleason Score and PSA.

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

Science.gov (United States)

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

Epigenetic Regulation in Prostate Cancer Progression.

Science.gov (United States)

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

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A. I. Neimark

2014-01-01

Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

[Radiotherapy in node-positive prostate cancer].

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Bottke, D; Bartkowiak, D; Bolenz, C; Wiegel, T

2016-03-01

There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options. This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy. The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery. There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

A Systematic Overview of Radiation Therapy Effects in Prostate Cancer

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Nilsson, Sten; Norlen, Bo Johan; Widmark, Anders

2004-01-01

A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients. There is a lack of properly controlled clinical trials in most important aspects of radiation therapy in prostate cancer. The conclusions reached can be summarized as follows: There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. Dose escalation to patients with intermediate-risk or high-risk disease can be performed with 3D conformal radiotherapy (photon or proton) boost, with Ir-192 high dose rate brachytherapy boost, or brachytherapy boost with permanent seed implantation. Despite an increased risk of urinary tract and/or rectal side effects, dose-escalated therapy can generally be safely delivered with all three techniques. There is some evidence that 3D conformal radiotherapy results in reduced late rectal toxicity and acute anal toxicity compared with radiotherapy administered with non-conformal treatment volumes. There is some evidence that postoperative external beam radiotherapy after radical prostatectomy in patients with

Sexual function with localized prostate cancer: active surveillance vs radical therapy

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van den Bergh, Roderick C. N.; Korfage, Ida J.; Roobol, Monique J.; Bangma, Chris H.; de Koning, Harry J.; Steyerberg, Ewout W.; Essink-Bot, Marie-Louise

2012-01-01

OBJECTIVE To compare sexual function of men with localized prostate cancer (PCa) on active surveillance (AS) with similar patients who received radical therapy. PATIENTS AND METHODS Two groups of men with screening-detected localized PCa were compared. The first were men on AS within the prospective

Late toxicity after conformal and intensity-modulated radiation therapy for prostate cancer. Impact of previous surgery for benign prostatic hyperplasia

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Odrazka, K.; Dolezel, M.; Vanasek, J.

2010-01-01

The objective of this study was to retrospectively compare late toxicity of conventional-dose three-dimensional conformal radiation therapy (3D-CRT) and high-dose intensity-modulated radiation therapy (IMRT) for prostate cancer. A total of 340 patients with T1-3 prostate cancer were treated with 3D-CRT (n=228) and IMRT (n=112). The median follow-up time was 5.9 years and 3.0 years, respectively. The prescription dose was 70 Gy for 3D-CRT and 78 Gy for IMRT. Late gastrointestinal (GI) and genitourinary (GU) toxicities were graded according to the Fox Chase modification of the Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. There was no difference between 3D-CRT and IMRT in the incidence of GI and GU toxicity at 3 years. On multivariate analysis, transurethral resection of prostate/open transvesical prostatectomy (TURP/TVPE) for benign prostatic hyperplasia, carried out before radiotherapy, significantly increased the risk of Grade ≥2 GU toxicity (risk ratio 1.88). Among patients who experienced TURP/TVPE, the 5-year actuarial likelihood of Grade 2-3 urinary incontinence was 23%, compared with 9% for those without prostate surgery (P=0.01). Tolerance of 3D-CRT and IMRT was similar, despite the use of high radiation dose with IMRT. Previous TURP/TVPE increased the risk of GU toxicity. (author)

Novel epigenetic target therapy for prostate cancer: a preclinical study.

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Ilaria Naldi

Full Text Available Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine, hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap and hormone refractory (DU145 prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs drug delivery system (DDS carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Novel epigenetic target therapy for prostate cancer: a preclinical study.

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Naldi, Ilaria; Taranta, Monia; Gherardini, Lisa; Pelosi, Gualtiero; Viglione, Federica; Grimaldi, Settimio; Pani, Luca; Cinti, Caterina

2014-01-01

Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

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Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

2016-03-31

There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer. Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated. Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.

Improved Beam Angle Arrangement in Intensity Modulated Proton Therapy Treatment Planning for Localized Prostate Cancer

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Cao, Wenhua; Lim, Gino J.; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

2015-01-01

Purpose: This study investigates potential gains of an improved beam angle arrangement compared to a conventional fixed gantry setup in intensity modulated proton therapy (IMPT) treatment for localized prostate cancer patients based on a proof of principle study. Materials and Methods: Three patients with localized prostate cancer retrospectively selected from our institution were studied. For each patient, IMPT plans were designed using two, three and four beam angles, respectively, obtained from a beam angle optimization algorithm. Those plans were then compared with ones using two lateral parallel-opposed beams according to the conventional planning protocol for localized prostate cancer adopted at our institution. Results: IMPT plans with two optimized angles achieved significant improvements in rectum sparing and moderate improvements in bladder sparing against those with two lateral angles. Plans with three optimized angles further improved rectum sparing significantly over those two-angle plans, whereas four-angle plans found no advantage over three-angle plans. A possible three-beam class solution for localized prostate patients was suggested and demonstrated with preserved dosimetric benefits because individually optimized three-angle solutions were found sharing a very similar pattern. Conclusions: This study has demonstrated the potential of using an improved beam angle arrangement to better exploit the theoretical dosimetric benefits of proton therapy and provided insights of selecting quality beam angles for localized prostate cancer treatment

Quantitative evaluation of bone metastases in patients with advanced prostate cancer during endocrine therapy

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Yahara, Jyunro

2003-01-01

A well-recognized difficulty in assessing the response to therapy for advanced prostate cancer is the infrequency of measurable metastatic disease. The most common metastatic site is bone, and it is manifested by diffuse ostoblastic lesions that cannot be measured reliably to allow for assessments of therapeutic benefits. We assessed the clinical usefulness of quantifying the extent of disease on bone scans in monitoring treatment response in patients with advance prostate cancer using computer-assisted image analysis. Percentage of the positive area on the bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program. Serial measurements of %PABS in 44 patients with bone metastasis from prostate cancer followed for a mean of 33 month (range 4 to 72) with hormonal therapy were compared with those of the extent of disease (EOD) grades in bone lesions and serum prostate specific antigen (PSA) levels according to treatment response. Serial measurements of EOD grades and %PABS in 13 patients with partial response (PR) disease and those in 12 patients with progressive disease (PD) who did not show bone metastasis progression demonstrated a downward trend during the treatment. On the other hand, changes of EOD grades and %PABS in the remaining 19 patients with PD who showed bone metastasis progression demonstrated an upward trend. Estimated survival curves showed that %PABS was a useful prognostic indicator, with the patients who showed a 25% decline in %PABS surviving longer than the patients who showed a less than 25% decline in %PABS after treatment (p=0.0207). The %PABS is a simple and reproducible estimate of the percentage of the skeleton involving tumors in patients with advanced prostate cancer, and serial measurements of %PABS can assist in monitoring the treatment response in patients with bone metastatic prostate cancer. (author)

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

Science.gov (United States)

2017-10-01

prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

Therapeutic effects of strontium-89 combined with endocrine therapy for treatment of bone metastasis in patients with prostate cancer

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Guo Deming

2009-01-01

Objective: To evaluate the effects of strontium-89 ( 89 Sr) combined with endocrine therapy for the treatment of bone metastasis in patients with advanced prostate cancer. Methods: 45 cases of prostate cancer with bone metastasis were randomly divided into 2 groups: patients in study group (23 cases) were given 89 Sr combined with endocrine therapy while patients in control group (22 cases) were given endocrine therapy only. The effect on pain relief, the serum PSA level, hemogram and biochemical indicators of hepatic and renal function were observed. Results: The pain degree was not statistically significant between two groups before treatment (P>0.05) and was statistically significant after treatment (P 89 Sr radionuclide combined with endocrine therapy was more effective than endocrine therapy alone in relief of the pain from bone metastasis and reduction of metastasis size in patients with advaced prostatic cancer. (authors)

Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

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Tsung-Yi Huang

2015-06-01

Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

Development of Personalized Cancer Therapy for Men with AdvancedProstate Cancer

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2016-10-01

propose to study the mechanism of pharmacologic inhibition of the MLL complex in prostate cancer cells 3) we will assess the in vivo efficacy of the...Project Goals: 1) Enroll patients with known or suspicious for prostate cancer in the NIH MRI /metabolic imaging program, 2) Whole exome and...Henderson 02/11/2014-01/31/2017 Project Goals: 1) Enroll patients with known or suspicious for prostate cancer in the NIH MRI /metabolic imaging program

Accuracy of Real-time Couch Tracking During 3-dimensional Conformal Radiation Therapy, Intensity Modulated Radiation Therapy, and Volumetric Modulated Arc Therapy for Prostate Cancer

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Wilbert, Juergen; Baier, Kurt; Hermann, Christian; Flentje, Michael; Guckenberger, Matthias

2013-01-01

Purpose: To evaluate the accuracy of real-time couch tracking for prostate cancer. Methods and Materials: Intrafractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study; prostate motion had been monitored with the Calypso System. An industrial robot moved a phantom along these trajectories, motion was detected via an infrared camera system, and the robotic HexaPOD couch was used for real-time counter-steering. Residual phantom motion during real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of 3-dimensional conformal radiation therapy (3D-CRT), step-and-shoot intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Results: Motion of the prostate was largest in the anterior–posterior direction, with systematic (∑) and random (σ) errors of 2.3 mm and 2.9 mm, respectively; the prostate was outside a threshold of 5 mm (3D vector) for 25.0%±19.8% of treatment time. Real-time tracking reduced prostate motion to ∑=0.01 mm and σ = 0.55 mm in the anterior–posterior direction; the prostate remained within a 1-mm and 5-mm threshold for 93.9%±4.6% and 99.7%±0.4% of the time, respectively. Without real-time tracking, pass rates based on a γ index of 2%/2 mm in film dosimetry ranged between 66% and 72% for 3D-CRT, IMRT, and VMAT, on average. Real-time tracking increased pass rates to minimum 98% on average for 3D-CRT, IMRT, and VMAT. Conclusions: Real-time couch tracking resulted in submillimeter accuracy for prostate cancer, which transferred into high dosimetric accuracy independently of whether 3D-CRT, IMRT, or VMAT was used.

Prostate Cancer Stem-Like Cells | Center for Cancer Research

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Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation

Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy.

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Morita, Masaru; Matsuura, Takeshi

2012-01-01

Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients' age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients' age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%). In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months' follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer.

Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy

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Masaru Morita

2012-01-01

Full Text Available Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients’ age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients’ age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%. In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months’ follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer.

Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

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Julia Lipianskaya

2014-08-01

Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

Decreased sexual capacity after external radiation therapy for prostate cancer impairs quality of life

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Helgason, Asgeir R.; Fredrikson, Mats; Adolfsson, Jan; Steineck, Gunnar

1995-01-01

Purpose: The aim of this study was to assess to what extent patients treated with radiation therapy for prostate cancer experience change in sexual functioning and to what extent this effects quality of life. Methods and Materials: Information was provided by 53 men treated with radiation therapy for localized prostate cancer. Assessment was made with the ''Radiumhemmets Scale of Sexual Functioning,'' which measures sexual desire, erectile capacity, orgasm, and to what extent a decrease in any of these aspects of sexual functioning affects quality of life. Function before treatment was assessed retrospectively. Results: Sexual desire diminished among 77% after treatment. The erection stiffness decreased in 77%. Before external radiation therapy, 66% had an erection usually sufficient for intercourse. Half of the men lost this ability after treatment. Of those retaining orgasm after treatment, 47% reported a decreased orgasmic pleasure and 91% a reduced ejaculation volume. Of all men, 50% reported that quality of life had decreased much or very much due to a decline in the erectile capacity following external radiation therapy. Conclusion: The results of the present study indicate that external radiation therapy for prostate cancer is associated with a reduction in sexual desire, erectile capacity, and orgasm functions. In a majority of patients this reduces quality of life. Previously, we may have underestimated the importance an intact sexual function has for the quality of life in this patient category of elderly men

National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

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Yang, David D. [Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Medicine, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Labe, Shelby A.; Nezolosky, Michelle D.; Vastola, Marie E.; King, Martin T.; Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Choueiri, Toni K. [Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Division of Urological Surgery, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Spratt, Daniel E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Feng, Felix Y. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Departments of Urology & Medicine and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California (United States); and others

2017-06-01

Purpose: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Methods and Materials: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Results: Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. Conclusions: ADT use in low-risk prostate cancer has declined nationally but may remain an issue

P52 Activation and Enzalutamide Therapy in Prostate Cancer

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2017-10-01

c-Myc:hnRNPA1 pathway regulates expression of androgen receptor splice variants and enzalutamide sensitivity in prostate cancer . Castration resistant... prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active... receptor splice variants and enzalutamide sensitivity in prostate cancer . • We discovered that quercetin, a naturally occurring polyphenolic compound

Localized field conformation radiotherapy combined with endocrine therapy for the treatment of prostate cancer

International Nuclear Information System (INIS)

Karasawa, Katsuyuki; Kaizu, Toshihide; Kurosaki, Hiromasa; Tanaka, Yoshiaki

1999-01-01

To improve the quality of life (QOL) of the patients with prostate cancer, we limit the radiotherapy target volume to the prostate and seminal vesicles while using endocrine therapy towards the disease outside the target volume. Radiotherapy technique was rotation conformation technique with computer-controlled multileaf collimators to the total doses of up to 66-70 Gy. Among 145 evaluable cases with the median age of 74, overall and cause-specific 5-year survival rates were 59.3% and 84.1%, respectively, and the relative survival rate of the Stage A-C cases was 100%. The two thirds (33/50) of the deaths were not of prostate cancer. The rate of severe complication was 1.4%. As for QOL, the rate of impotence was 90%, however, the patients' overall satisfaction towards the treatment was 90%. From this analysis, this combined treatment seems beneficial in the treatment of prostate cancer. (author)

Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

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Waldemar Białek

2016-12-01

Full Text Available Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

Treatment of prostatic cancer using daily intermittent multiportal therapy (DIMT) technique

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Suzuki, Keishiro; Irie, Goro (Hokkaido Univ., Sapporo (Japan). School of Medicine); Shirato, Hiroki; Takayama, Naohisa; Sutoh, Susumu

1992-06-01

In the treatment of prostatic cancer using a newly proposed intermittent multiportal therapy (DIMT), acute reactions, change in tumor marker levels, and complications more than 6 months after treatment were evaluated. From June 1989 to September 1990, 26 patients with prostatic cancer (stage A2, 3 patients; B, 9; C, 2; D, 10; recurrence, 2) were treated. Fifteen patients were followed up for more than one year, with a mean period of 11.6 months. The treatment schedule is 52.5 Gy in 16 fractions in 4 weeks for radical treatment, and 30.0 Gy in 8 fractions in 2 weeks for palliative treatment. The 360 degree rotation about the patient was divided into 16 fractions, and 2 opposing fractions were used in one day as parallel opposed portals to treat the target volume. The fractions were serially treated one per day, so that 8 treatment days produced a total dose of distribution similar to that for conventional conformational therapy. The size of the irradiation field varied from 6 x 6 cm to 9 x 9 cm. No hormonal therapy was performed for stage A2 or B. Acute effect was minimal including skin erythema 2/26 (7%), pollakisuria 1/26 (4%), mild symptoms due to acute proctitis 9/26 (35%). Abnormality high PSA and/or PAP levels returned to the normal range after the treatment in 7 of 10 patients. Local recurrence was detected in 1 patient with stage D, 15 months after completion of therapy, but 21 other patients continued for more than 6 months with no clinical evidence of local recurrence. No residual disease was detected by biopsy undertaken in 10 patients after more than 6 months. No severe complication was detected after more than 6 months except in 1 patient who needed colostomy for the relief of rectal bleeding. DIMT can have the total dose distribution similar to that of conventional conformational therapy without specific devices. Initial results on prostatic cancer treatment were encouraging. (J.P.N.).

Proton Therapy Coverage for Prostate Cancer Treatment

International Nuclear Information System (INIS)

Vargas, Carlos; Wagner, Marcus; Mahajan, Chaitali; Indelicato, Daniel; Fryer, Amber; Falchook, Aaron; Horne, David C.; Chellini, Angela; McKenzie, Craig C.; Lawlor, Paula C.; Li Zuofeng; Lin Liyong; Keole, Sameer

2008-01-01

Purpose: To determine the impact of prostate motion on dose coverage in proton therapy. Methods and Materials: A total of 120 prostate positions were analyzed on 10 treatment plans for 10 prostate patients treated using our low-risk proton therapy prostate protocol (University of Florida Proton Therapy Institute 001). Computed tomography and magnetic resonance imaging T 2 -weighted turbo spin-echo scans were registered for all cases. The planning target volume included the prostate with a 5-mm axial and 8-mm superoinferior expansion. The prostate was repositioned using 5- and 10-mm one-dimensional vectors and 10-mm multidimensional vectors (Points A-D). The beam was realigned for the 5- and 10-mm displacements. The prescription dose was 78 Gy equivalent (GE). Results: The mean percentage of rectum receiving 70 Gy (V 70 ) was 7.9%, the bladder V 70 was 14.0%, and the femoral head/neck V 50 was 0.1%, and the mean pelvic dose was 4.6 GE. The percentage of prostate receiving 78 Gy (V 78 ) with the 5-mm movements changed by -0.2% (range, 0.006-0.5%, p > 0.7). However, the prostate V 78 after a 10-mm displacement changed significantly (p 78 coverage had a large and significant reduction of 17.4% (range, 13.5-17.4%, p 78 coverage of the clinical target volume. The minimal prostate dose was reduced 33% (25.8 GE), on average, for Points A-D. The prostate minimal dose improved from 69.3 GE to 78.2 GE (p < 0.001) with realignment for 10-mm movements. Conclusion: The good dose coverage and low normal doses achieved for the initial plan was maintained with movements of ≤5 mm. Beam realignment improved coverage for 10-mm displacements

The 5th Conference on Asian Trends in Prostate Cancer Hormone Therapy.

Science.gov (United States)

Akaza, Hideyuki; Moore, Malcolm A; Chang, Shu-Jen; Cheng, Christopher; Choi, Han Yong; Esuvaranathan, Kesavan; Hinotsu, Shiro; Hong, Sung-Joon; Kim, Choung-Soo; Kim, Wun-Jae; Murai, Masaru; Naito, Seiji; Soebadi, Doddy; Song, Jae-Mann; Umbas, Rainy; Usami, Michiyuki; Xia, Shujie; Yang, Chi-Rei

2007-01-01

The Conference on Asian Trends in Prostate Cancer Hormone Therapy is an annual forum for Asian urologists now in its 5th year. The 2006 conference, held in Bali, Indonesia, was attended by 27 leading urologic oncologists from China, Indonesia, Japan, Korea, Singapore, and Taiwan and featured a packed program of presentations and discussions on a wide range of topics such as relationships among clinicians and the newly opened Asia Regional Office for Cancer Control of the International Union Against Cancer (UICC), detection rates of prostate cancer by biopsy in each of the 6 Asian countries, and favored treatment modalities for hormone-refractory prostate cancer (HRPC) in each country. The first session of the conference kicked off with a keynote lecture entitled "Activities of the UICC ARO". UICC's new office will be the nerve center for its activities in the Asia region. Along with the Asian Pacific Organization for Cancer Prevention (APOCP), UICC aims to shift the focus of attention to cancer control. As such APOCP's long-running publication the APJCP is to be re-launched as the Asian Pacific Journal of Cancer Control. Although UICC is primarily concerned with cancer, several risk factors for cancer are common also to other non-communicable diseases such as diabetes and heart disease, and an important strategy is to implement measures to control these various pathologic conditions as a whole. Apart from contributing to an Asian prostate cancer registry the UICC-ARO will provide training courses, working groups, and assistance in collecting and processing data. The keynote lecture was followed by a roundtable discussion on possible ways in which clinicians from each Asian country can work with UICC. A number of suggestions were put forth including better registration, epidemiology research, possible implementation of UICC prostate cancer guidelines, early detection and screening, and roles of diet and phytotherapy. The underlying reasons for the large but

Management of patients with advanced prostate cancer

DEFF Research Database (Denmark)

Gillessen, S; Omlin, A; Attard, G

2015-01-01

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration......-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion...

Advanced research on separating prostate cancer stem cells

International Nuclear Information System (INIS)

Hao Yumei; He Xin; Song Naling

2013-01-01

Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

Gene Polymorphism-related Individual and Interracial Differences in the Outcomes of Androgen Deprivation Therapy for Prostate Cancer.

Science.gov (United States)

Fujimoto, Naohiro; Shiota, Masaki; Tomisaki, Ikko; Minato, Akinori

2017-06-01

Among patients with prostate cancer, the prognosis after androgen deprivation therapy differs significantly among individuals and among races; however, the reasons underlying these differences are poorly understood. Several single nucleotide polymorphisms in genes associated with prostate cancer progression or castration resistance might serve as the host factor that influences prognosis and, thus, accounts for these individual and racial gaps in treatment outcomes. Accordingly, single nucleotide polymorphisms associated with treatment outcomes could be used as predictive and/or prognostic biomarkers for patient stratification and to identify personalized treatment and follow-up protocols. The present review has summarized the genetic polymorphisms that have been reported to associate with androgen deprivation therapy outcomes among patients with prostate cancer and compared the allele frequencies among different ethnic groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

Science.gov (United States)

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

The value of MRI three-dimensional reconstruction in diagnosis and therapy of prostate cancer

International Nuclear Information System (INIS)

Li Feiyu; Wang Xiaoying; Xu Yufeng; Xiao Jiangxi; Jiang Xuexiang

2006-01-01

Objective: To evaluate three-dimensional reconstruction of MRI images in diagnosis and therapy of prostate cancer. Methods: Twenty-eight patients with proven prostate cancers were recruited in this study. Seventeen of them were diagnosed as having prostate cancer according to the ultrasound guided systemic biopsy. Their MR examinations showed fourteen lesions in the peripheral zone and three in the central gland of the prostate. The other eleven patients underwent MR examination after a period of treatment, including endocrinetherapy and brachytherapy. Using endorectal coil, a series of T 2 -weighted images were acquired on the axial plane. These source images were processed by 3D-Doctor software to reconstruct into three-dimensional images. Results: In the fourteen patients with peripheral zone cancer, reconstruction images could display the 3D regions of cancer and the involvement of capsular. The outspread of central gland and the compression of peripheral zone in patients with central gland cancer could be revealed in the same way. The volumetric changes of the lesion and the prostate after endocrinetherapy could also be perceived through these 3 D images. Similarly, radioactive seeds were revealed in a spatial manner that could be easily evaluated. Conclusion: Three-dimensional reconstruction images were obtained in all patients. They were able to provide stereotyped information about the lesions and their surrounding tissues. MRI three-dimensional reconstruction can be an adjunctive tool in the evaluation of prostate lesions. (authors)

A Patterns of Care Study of the Various Radiation Therapies for Prostate Cancer among Korean Radiation Oncologists in 2006

International Nuclear Information System (INIS)

Kim, Jin Hee; Kim, Jae Sung; Ha, Sung Whan

2008-01-01

To conduct a nationwide academic hospital patterns of the practice status and principles of radiotherapy for prostate cancer. The survey will help develop the framework of a database of Korean in Patterns of Case Study. A questionnaire about radiation treatment status and principles was sent to radiation oncologists in charge of prostate cancer treatment at thirteen academic hospitals in Korea. The data was analyzed to find treatment principles among the radiation oncologists when treating prostate cancer. The number of patients with prostate cancer and treated with radiation ranged from 60 to 150 per academic hospital in Seoul City and 10 to 15 outside of Seoul City in 2006. The primary diagnostic methods of prostate cancer included the ultrasound guided biopsy on 6 to 12 prostate sites (mean=9), followed by magnetic resonance imaging and a whole body bone scan. Internal and external immobilizations were used in 61.5% and 76.9%, respectively, with diverse radiation targets. Whole pelvis radiation therapy (dose ranging from 45.0 to 50.4 Gy) was performed in 76.9%, followed by the irradiation of seminal vesicles (54.0∼73.8 Gy) in 92.3%. The definitive radiotherapy doses were increased as a function of risk group, but the range of radiation doses was wide (60.0 to 78.5 Gy). Intensity modulated radiation therapy using doses greater than 70 Gy, were performed in 53.8% of academic hospitals. In addition, the simultaneous intra-factional boost (SIB) technique was used in three hospitals; however, the target volume and radiation dose were diverse. Radiation therapy to biochemical recurrence after a radical prostatectomy was performed in 84.6%; however, the radiation dose was variable and the radiation field ranged from whole pelvis to prostate bed. The results of this study suggest that a nationwide Korean Patterns of Care Study is necessary for the recommendation of radiation therapy guidelines of prostate cancer

Radiotherapy and hormone therapy in intermediate risk prostate cancer: a critical review

International Nuclear Information System (INIS)

Franco, Rejane Carolina; Souhami, Luis

2015-01-01

Introduction: The standard treatment for patients with high risk prostate cancer is the combined use of radiation therapy (RT ) and hormone therapy (HT). In regards to patients stratified as intermediate risk, the use of HT associated with RT remains controversial, and its use should be carefully planned and based on available evidence. Objective: To critically assess results of randomized studies published in the literature that associated the use of HT of short duration with an average period of 6 months with RT in the treatment of patients with localized prostate cancer classified as intermediate risk. Method: Only randomized studies comparing these treatments were eligible for this review. A structured search through 'PubMed' was carried out using the terms 'androgen suppression therapy', 'radiotherapy', 'randomized trials', 'phase 3 trials', 'prostate cancer' and 'intermediate risk'. Results: Four randomized studies comparing RT alone to RT plus short course HT were found and selected. The majority of the trials had a mixed population of intermediate and high risk disease and did not include patients with only intermediate risk. Despite that, there appears to be a significant benefit for the combined approach regarding disease-free survival, biochemical free survival and overall survival. Conclusion: The randomized studies published so far suggest improved outcomes for the group of patients receiving RT and short course HT. Data from randomized trials comparing RT alone to RT and short course HT in patients with intermediate risk only are forthcoming. (author)

Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy.

Directory of Open Access Journals (Sweden)

Xiaoqiang Sun

Full Text Available Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.

From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

International Nuclear Information System (INIS)

Thobe, Megan N.; Clark, Robert J.; Bainer, Russell O.; Prasad, Sandip M.; Rinker-Schaeffer, Carrie W.

2011-01-01

Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

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Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

2011-01-27

Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study

International Nuclear Information System (INIS)

Margalit, Danielle N.; Kasperzyk, Julie L.; Martin, Neil E.; Sesso, Howard D.; Gaziano, John Michael; Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.

2012-01-01

Purpose: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians’ Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. Methods and Materials: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. Results: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42–1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87–95%) in the beta-carotene group and 89% (95% CI, 84–93%) in the placebo group. Conclusion: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.

The bicalutamide Early Prostate Cancer Program. Demography

DEFF Research Database (Denmark)

See, W A.; McLeod, D; Iversen, P

2001-01-01

BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up...... to investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical...... areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study...

Key papers in prostate cancer.

Science.gov (United States)

Rodney, Simon; Shah, Taimur Tariq; Patel, Hitendra R H; Arya, Manit

2014-11-01

Prostate cancer is the most common cancer and second leading cause of death in men. The evidence base for the diagnosis and treatment of prostate cancer is continually changing. We aim to review and discuss past and contemporary papers on these topics to provoke debate and highlight key dilemmas faced by the urological community. We review key papers on prostate-specific antigen screening, radical prostatectomy versus surveillance strategies, targeted therapies, timing of radiotherapy and alternative anti-androgen therapeutics. Previously, the majority of patients, irrespective of risk, underwent radical open surgical procedures associated with considerable morbidity and mortality. Evidence is emerging that not all prostate cancers are alike and that low-grade disease can be safely managed by surveillance strategies and localized treatment to the prostate. The question remains as to how to accurately stage the disease and ultimately choose which treatment pathway to follow.

Organoid cultures derived from patients with advanced prostate cancer

NARCIS (Netherlands)

Gao, Dong; Vela, Ian; Sboner, Andrea; Iaquinta, Phillip J; Karthaus, Wouter R; Gopalan, Anuradha; Dowling, Catherine; Wanjala, Jackline N; Undvall, Eva A; Arora, Vivek K; Wongvipat, John; Kossai, Myriam; Ramazanoglu, Sinan; Barboza, Luendreo P; Di, Wei; Cao, Zhen; Zhang, Qi Fan; Sirota, Inna; Ran, Leili; MacDonald, Theresa Y; Beltran, Himisha; Mosquera, Juan-Miguel; Touijer, Karim A; Scardino, Peter T; Laudone, Vincent P; Curtis, Kristen R; Rathkopf, Dana E; Morris, Michael J; Danila, Daniel C; Slovin, Susan F; Solomon, Stephen B; Eastham, James A; Chi, Ping; Carver, Brett; Rubin, Mark A; Scher, Howard I; Clevers, Hans; Sawyers, Charles L; Chen, Yu

2014-01-01

The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and

Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy

Directory of Open Access Journals (Sweden)

Moyad MA

2016-08-01

Full Text Available Mark A Moyad,1 Robert U Newton,2 Ulf W Tunn,3 Damian Gruca4 1Department of Urology, University of Michigan Medical Center, Ann Arbor, MI, USA; 2Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia; 3Urological Clinic, Facharztzentrum Academic Hospital Sana Klinikum Offenbach, Offenbach/Main, 4Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany Abstract: Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to

Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy

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Jiun-Hung Geng

2016-11-01

Full Text Available Aberrant Wnt signaling has been associated with many types of cancer. However, the association of inherited Wnt pathway variants with clinical outcomes in prostate cancer patients receiving androgen deprivation therapy (ADT has not been determined. Here, we comprehensively studied the contribution of common single nucleotide polymorphisms (SNPs in Wnt pathway genes to the clinical outcomes of 465 advanced prostate cancer patients treated with ADT. Two SNPs, adenomatous polyposis coli (APC rs2707765 and rs497844, were significantly (p ≤ 0.009 and q ≤ 0.043 associated with both prostate cancer progression and all-cause mortality, even after multivariate analyses and multiple testing correction. Patients with a greater number of favorable alleles had a longer time to disease progression and better overall survival during ADT (p for trend ≤ 0.003. Additional, cDNA array and in silico analyses of prostate cancer tissue suggested that rs2707765 affects APC expression, which in turn is correlated with tumor aggressiveness and patient prognosis. This study identifies the influence of inherited variants in the Wnt pathway on the efficacy of ADT and highlights a preclinical rationale for using APC as a prognostic marker in advanced prostate cancer.

AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

Science.gov (United States)

Antonarakis, Emmanuel S

2018-01-18

The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

Hyaluronan-Based Therapy for Metastatic Prostate Cancer

Science.gov (United States)

2016-09-01

Importantly, the system can target CD44+ prostate cancer stem cells through intrinsic HA-CD44 receptor interactions and deliver drugs directly to...be released by enzymatic degradation via HYAL1. Importantly, the system can target CD44+ prostate cancer stem cells through intrinsic HA-CD44...In Situ DNA Strand Break Labeling (TUNEL assay)—Tumor tissues were recovered from euthanized animals. Sections (5 μm) were cut from 10% neutral

Durable remission of leptomeningeal metastases from hormone-responsive prostate cancer.

Science.gov (United States)

Zhang, Meng; Mahta, Ali; Kim, Ryan Y; Akar, Serra; Kesari, Santosh

2012-06-01

Prostate cancer is rarely associated with leptomeningeal metastasis. An 87-year-old man with a history of prostate cancer presented with leptomeningeal metastasis. He received hormonal therapy with leuprolide. Subsequently, he achieved an impressive response, indicated by a constant fall in his PSA levels and by the stabilization of leptomeningeal disease and clinical improvement. Hormonal therapy may be effective in inducing remission in hormone-sensitive prostate cancer with leptomeningeal metastasis.

Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events

Energy Technology Data Exchange (ETDEWEB)

Bosco, Cecilia, E-mail: Cecilia.t.bosco@kcl.ac.uk [Translational Oncology & Urology Research (TOUR), Division of Cancer Studies, King' s College London, London (United Kingdom); Garmo, Hans [Translational Oncology & Urology Research (TOUR), Division of Cancer Studies, King' s College London, London (United Kingdom); Regional Cancer Centre, Uppsala, Akademiska Sjukhuset, Uppsala (Sweden); Adolfsson, Jan [CLINTEC Department, Karolinska Institutet, Stockholm (Sweden); Stattin, Pär [Department of Surgical Sciences, Uppsala University, Uppsala (Sweden); Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå (Sweden); Holmberg, Lars [Translational Oncology & Urology Research (TOUR), Division of Cancer Studies, King' s College London, London (United Kingdom); Regional Cancer Centre, Uppsala, Akademiska Sjukhuset, Uppsala (Sweden); Department of Surgical Sciences, Uppsala University, Uppsala (Sweden); Nilsson, Per; Gunnlaugsson, Adalsteinn [Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund University, Lund (Sweden); Widmark, Anders [Department of Radiation Sciences, Oncology, Umeå University, Umeå (Sweden); Van Hemelrijck, Mieke [Translational Oncology & Urology Research (TOUR), Division of Cancer Studies, King' s College London, London (United Kingdom); Institute of Environmental Medicine, Karolinska Institute, Stockholm (Sweden)

2017-04-01

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa). Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression. Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis. Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.

Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events

International Nuclear Information System (INIS)

Bosco, Cecilia; Garmo, Hans; Adolfsson, Jan; Stattin, Pär; Holmberg, Lars; Nilsson, Per; Gunnlaugsson, Adalsteinn; Widmark, Anders; Van Hemelrijck, Mieke

2017-01-01

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa). Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression. Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis. Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Freytag, Svend O., E-mail: sfreyta1@hfhs.org [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Stricker, Hans [Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan (United States); Lu, Mei [Public Health Sciences, Henry Ford Health System, Detroit, Michigan (United States); Elshaikh, Mohamed; Aref, Ibrahim; Pradhan, Deepak; Levin, Kenneth; Kim, Jae Ho [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Peabody, James [Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan (United States); Siddiqui, Farzan; Barton, Kenneth; Pegg, Jan; Zhang, Yingshu; Cheng, Jingfang [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Oja-Tebbe, Nancy; Bourgeois, Renee [Public Health Sciences, Henry Ford Health System, Detroit, Michigan (United States); Gupta, Nilesh; Lane, Zhaoli [Pathology, Henry Ford Health System, Detroit, Michigan (United States); Rodriguez, Ron [Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

2014-06-01

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

International Nuclear Information System (INIS)

Freytag, Svend O.; Stricker, Hans; Lu, Mei; Elshaikh, Mohamed; Aref, Ibrahim; Pradhan, Deepak; Levin, Kenneth; Kim, Jae Ho; Peabody, James; Siddiqui, Farzan; Barton, Kenneth; Pegg, Jan; Zhang, Yingshu; Cheng, Jingfang; Oja-Tebbe, Nancy; Bourgeois, Renee; Gupta, Nilesh; Lane, Zhaoli; Rodriguez, Ron; DeWeese, Theodore

2014-01-01

Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer

Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report.

Science.gov (United States)

Wang, Chiachien Jake; Ying, James; Kapur, Payal; Wohlfeld, Bryan; Roehrborn, Claus; Kim, Dong W Nathan

2016-01-01

Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients.

Potency preservation following stereotactic body radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Obayomi-Davies, Olusola; Pahira, John; McGeagh, Kevin G; Collins, Brian T; Kowalczyk, Keith; Bandi, Gaurav; Kumar, Deepak; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P; Chen, Leonard N; Bhagat, Aditi; Wright, Henry C; Uhm, Sunghae; Kim, Joy S; Yung, Thomas M; Lei, Siyuan; Batipps, Gerald P

2013-01-01

Erectile dysfunction after prostate radiation therapy remains an ongoing challenge and critical quality of life issue. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT impotency would be higher than conventional radiation therapy approaches. This study sought to evaluate potency preservation and sexual function following SBRT for prostate cancer. Between February 2008 and March 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. Potency was defined as the ability to have an erection firm enough for intercourse with or without sexual aids while sexual activity was defined as the ability to have an erection firm enough for masturbation and foreplay. Patients who received androgen deprivation therapy (ADT) were excluded from this study. Ninety-seven hormone-naïve men were identified as being potent at the initiation of therapy and were included in this review. All patients were treated to 35–36.25 Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Prostate specific antigen (PSA) and total testosterone levels were obtained pre-treatment, every 3 months for the first year and every 6 months for the subsequent year. Sexual function was assessed with the Sexual Health Inventory for Men (SHIM), the Expanded Prostate Index Composite (EPIC)-26 and Utilization of Sexual Medication/Device questionnaires at baseline and all follow-up visits. Ninety-seven men (43 low-, 50 intermediate- and 4 high-risk) at a median age of 68 years (range, 48–82 years) received SBRT. The median pre-treatment PSA was 5.9 ng/ml and the minimum follow-up was 24 months. The median pre-treatment total serum testosterone level was 11.4 nmol/L (range, 4.4-27.9 nmol/L). The median baseline SHIM was 22 and 36% of patients utilized sexual aids prior to treatment. Although potency rates declined following

Does tadalafil prevent erectile dysfunction in patients undergoing radiation therapy for prostate cancer?

NARCIS (Netherlands)

L. Incrocci (Luca)

2014-01-01

textabstractA recently published paper addressed the interesting topic of prevention of erectile dysfunction (ED) with tadalafil, a phosphodiesterase-type 5 inhibitor (PDE5i) in patients undergoing radiation therapy for localized prostate cancer. ^[1]Tadalafil 5 mg or placebo was

The Role of Estrogen Receptor β in Prostate Cancer

OpenAIRE

Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

2014-01-01

Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the re...

Progress of radiolabelled bombesin in diagnosis and treatment of prostate cancer

International Nuclear Information System (INIS)

Xing Yan; Zhao Jihua

2010-01-01

Studies show that high expression of bombesin exist in the face of many kind of tumors such as prostate cancer, so bombesin and its receptor can be used as target in radionuclide receptor imaging and targeted therapy of tumor, and become the focus of prostate cancer research. This article reviews the progress of radiolabelled bombesin in prostate cancer imaging and therapy. (authors)

Five-Year Outcomes from 3 Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Mendenhall, Nancy P., E-mail: menden@shands.ufl.edu [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Hoppe, Bradford S.; Nichols, Romaine C.; Mendenhall, William M.; Morris, Christopher G.; Li, Zuofeng; Su, Zhong [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Williams, Christopher R.; Costa, Joseph [Division of Urology, College of Medicine, University of Florida, Jacksonville, Florida (United States); Henderson, Randal H. [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

2014-03-01

Purpose: To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. Methods and Materials: A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. Results: Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. Conclusions: Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes.

Five-Year Outcomes from 3 Prospective Trials of Image-Guided Proton Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Mendenhall, Nancy P.; Hoppe, Bradford S.; Nichols, Romaine C.; Mendenhall, William M.; Morris, Christopher G.; Li, Zuofeng; Su, Zhong; Williams, Christopher R.; Costa, Joseph; Henderson, Randal H.

2014-01-01

Purpose: To report 5-year clinical outcomes of 3 prospective trials of image-guided proton therapy for prostate cancer. Methods and Materials: A total of 211 prostate cancer patients (89 low-risk, 82 intermediate-risk, and 40 high-risk) were treated in institutional review board-approved trials of 78 cobalt gray equivalent (CGE) in 39 fractions for low-risk disease, 78 to 82 CGE for intermediate-risk disease, and 78 CGE with concomitant docetaxel therapy followed by androgen deprivation therapy for high-risk disease. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Median follow-up was 5.2 years. Results: Five-year rates of biochemical and clinical freedom from disease progression were 99%, 99%, and 76% in low-, intermediate-, and high-risk patients, respectively. Actuarial 5-year rates of late CTCAE, version 3.0 (or version 4.0) grade 3 gastrointestinal and urologic toxicity were 1.0% (0.5%) and 5.4% (1.0%), respectively. Median pretreatment scores and International Prostate Symptom Scores at >4 years posttreatment were 8 and 7, 6 and 6, and 9 and 8, respectively, among the low-, intermediate-, and high-risk patients. There were no significant changes between median pretreatment summary scores and Expanded Prostate Cancer Index Composite scores at >4 years for bowel, urinary irritative and/or obstructive, and urinary continence. Conclusions: Five-year clinical outcomes with image-guided proton therapy included extremely high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes. Further follow-up and a larger patient experience are necessary to confirm these favorable outcomes

Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

International Nuclear Information System (INIS)

Tendulkar, Rahul D.; Hunter, Grant K.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May; Stephenson, Andrew J.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

2013-01-01

Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not

Testicular Metastasis of Prostate Cancer: A Case Report

Directory of Open Access Journals (Sweden)

Ayumu Kusaka

2014-09-01

Full Text Available The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

Radical prostatectomy for high-risk prostate cancer.

Science.gov (United States)

Yossepowitch, Ofer; Eastham, James A

2008-06-01

Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

Recent Advances in Prostate Cancer Treatment and Drug Discovery

Directory of Open Access Journals (Sweden)

Ekaterina Nevedomskaya

2018-05-01

Full Text Available Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC. Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

Role of the Technical Aspects of Hypofractionated Radiation Therapy Treatment of Prostate Cancer: A Review

Energy Technology Data Exchange (ETDEWEB)

Clemente, Stefania, E-mail: clemente_stefania@libero.it [Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata Rionero in Vulture, Potenza (Italy); Nigro, Roberta [Azienda Sanitaria Locale Rieti, Roma (Italy); Oliviero, Caterina [Istituto di Ricovero e Cura a Carattere Scientifico Centro di Riferimento Oncologico della Basilicata Rionero in Vulture, Potenza (Italy); Marchioni, Chiara [Azienda Sanitaria Locale Rieti, Roma (Italy); Esposito, Marco [Azienda Sanitaria, Firenze (Italy); Giglioli, Francesca Romana [Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino (Italy); Mancosu, Pietro [Humanitas Clinical and Research Hospital, Rozzano, Milano (Italy); Marino, Carmelo [Humanitas Centro Catanese di Oncologia, Catania (Italy); Russo, Serenella [Azienda Sanitaria, Firenze (Italy); Stasi, Michele [Azienda Ospedaliera Ordine Mauriziano di Torino, Torino (Italy); Strigari, Lidia [Istituto Nazionale Tumori Regina Elena, Roma (Italy); Veronese, Ivan [Universita' degli Studi di Milano, Milano (Italy); Landoni, Valeria [Istituto Nazionale Tumori Regina Elena, Roma (Italy)

2015-01-01

The increasing use of moderate (<35 fractions) and extreme (<5 fractions) hypofractionated radiation therapy in prostate cancer is yielding favorable results, both in terms of maintained biochemical response and toxicity. Several hypofractionation (HF) schemes for the treatment of prostate cancer are available, although there is considerable variability in the techniques used to manage intra-/interfraction motion and deliver radiation doses. We performed a review of the published studies on HF regimens as a topic of interest for the Stereotactic Ablative Radiotherapy working group, which is part of the Italian Association of Medical Physics. Aspects of organ motion management (imaging for contouring, target volume definition, and rectum/bladder preparation) and treatment delivery (prostate localization, image guided radiation therapy strategy and frequency) were evaluated and categorized to assess outcome relative to disease control and toxicity. Despite the heterogeneity of the data, some interesting trends that emerged from the review might be useful in identifying an optimum HF strategy.

Erectile Function, Incontinence, and Other Quality of Life Outcomes Following Proton Therapy for Prostate Cancer in Men 60 Years Old and Younger

OpenAIRE

Hoppe, Bradford S; Nichols, Romaine C; Henderson, Randal H; Morris, Christopher G; Williams, Christopher R; Costa, Joseph; Marcus, Robert B; Mendenhall, William M; Li, Zuofeng; Mendenhall, Nancy P

2012-01-01

BACKGROUND This study sought to evaluate patient-reported health-related quality of life following proton therapy for prostate cancer in men ≤60 years old. METHODS Between August 2006 and January 2010, 262 hormone-naive men ≤60 years old were treated with definitive proton therapy for prostate cancer. Before treatment and every 6 months after treatment, patients filled out the Expanded Prostate Index Composite (EPIC) and the International Index of Erectile Function (IIEF) questionnaires. Pote...

Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

International Nuclear Information System (INIS)

Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

2014-01-01

Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

Exosomes in diagnosis and therapy of prostate cancer

OpenAIRE

Pan, Jun; Ding, Meng; Xu, Kai; Yang, Chunhua; Mao, Li-Jun

2017-01-01

Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the ...

Robotic radiotherapy for prostate cancer with CyberKnife

International Nuclear Information System (INIS)

Hannoun-Levi, J.M.; Benezery, K.; Bondiau, P.Y.; Marcie, S.; Gerard, J.P.; Chamorey, E.

2007-01-01

After 3D conformal radiation therapy without and with modulated intensity, image-guided radiation therapy represents a new technological step. Should prostate cancer treatment using radiotherapy with the CyberKnife robotic system be considered as a new treatment and then investigated through classical clinical research procedure rather than a technical improvement of an already validated treatment? After a general presentation of the CyberKnife, the authors focused on prostate cancer treatment assuming that, according to dosimetric and biological considerations, the treatment by robotic system appears comparable to high dose rate brachytherapy. For prostate cancer treatment are discussed: biological rational for hypo fractionated treatment, high dose rate brachytherapy boost and interest of dose escalation. A comparison is presented between CyberKnife and other validated treatment for prostate cancer (radical prostatectomy, 3D conformal radiation therapy and low and high dose rate brachytherapy). In summary, CyberKnife treatment could be considered as a technical improvement of an already validated treatment in order to deliver a prostate boost after pelvic or peri-prostatic area irradiation. However, the clinical, biological and economical results must be precisely analyzed and could be assessed in the frame of a National Observatory based on shared therapeutic program. (authors)

Efficacy of c-Met inhibitor for advanced prostate cancer

International Nuclear Information System (INIS)

Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

2010-01-01

Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

International Nuclear Information System (INIS)

Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham; Kuk, Deborah; Zhang, Zhigang; Zelefsky, Michael J.

2013-01-01

Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy

Clinical observation on strontium-89-chloride therapy in elder patients with prostate cancer for palliation of pain from bone metastases

International Nuclear Information System (INIS)

Chen Weimin; Lin Tiansheng; Wang Shen; Chen Tanying

2006-01-01

Objective: To estimate clinical curative efficacy and adverse reaction of 89 Sr-chloride therapy for palliation of pain from bone metastases in the older patients with prostate cancer. Methods: 48 cases of older patients with metastatic prostate cancer with bone pain were studied after androgen deprivation therapy, 89 Sr- chloride were administrated iv for the palliative treatment of metastatic bone pain. The curative effects in patients were investigated, including palliation of pain, change of metastatic focus, the tumor sign of PSA, and the adverse reaction. Results: After 89 Sr-chloride therapy, the total palliation rate was 89.6%, inefficiency rate was 10.4%, while metastatic focus and PSA decreased to some extent. No severe adverse reaction occurred. Conclusions: It is shown that the curative efficacy of acesodyne is evident after 89 Sr-chloride therapy in older patients suffering from bone metastase with prostate cancer. It is an effective therapeutic method for the palliation of pain from bone metastases especially to the older patients with multiple metastatases. (authors)

[Molecular biology of castration-resistant prostate cancer].

Science.gov (United States)

Doucet, Ludovic; Terrisse, Safae; Gauthier, Hélène; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

2015-06-01

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Radiation therapy for oligorecurrence in prostate cancer. Preliminary results of our centre.

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González Ruiz de León, C; Ramírez Backhaus, M; Sobrón Bustamante, M; Casaña, J; Arribas, L; Rubio-Briones, J

2017-12-01

There is growing interest in the use of more aggressive therapeutic modalities for treating metastatic prostate cancer. In this study, we examine the use of stereotactic body radiation therapy (SBRT) for patients with oligorecurrent prostate cancer. We analysed the biochemical response and toxicity of patients who underwent this therapy at our centre. We selected patients who experienced oligorecurrence between January 2015 to December 2016 and were administered SBRT. The association of androgen deprivation (AD) was left in each case to the decision of the tumour committee. We describe the clinical situation at diagnosis of oligorecurrence, the treatment administered and the biochemical response. We considered a biochemical response to be a 50% reduction in the absolute prostate-specific antigen (PSA) readings. SBRT was administered to 11 patients with bone (82%) and/or lymph node oligometastasis (18%). The treatment regimen for bone oligometastasis was 27Gy divided into 3 sessions, while the treatment for lymph node oligometastasis reached 70Gy. Seven patients had no treatment at the time of diagnosis, 2 were in the castration-resistant phase, 1 patient was in the off phase of intermittent AD, and 1 patient had adjuvant AD for pN1. Seven patients presented a biochemical response with a PSA reduction of 75-100%. The response was not assessable in 4 patients due to the continuing adjuvant AD. With a mean follow-up of 10.5 months, only 2 patients had progressed. Grade 1 gastrointestinal toxicity was detected in only 1 patient. Our data suggest that the use of SBRT in carefully selected patients with metastatic oligorecurrence of prostate cancer can achieve biochemical response and potentially delay progression and the use of systemic treatments. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Low Incidence of Fatigue after Hypofractionated Stereotactic Body Radiation Therapy (SBRT for Localized Prostate Cancer

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Chiranjeev eDash

2012-10-01

Full Text Available Background: Fatigue is a common side-effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment.Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months follow-up were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post-SBRT.Results: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (p=0.02. Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA levels, testosterone levels, and tumor stage were not associated with fatigue. Conclusion: This is the first study to investigate fatigue as a side-effect of SBRT. In contrast to standard radiation therapy, results suggest SBRT-related fatigue is short-term rather than a long-term side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians.

Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

International Nuclear Information System (INIS)

Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

2014-01-01

Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment

Urethral Pain Among Prostate Cancer Survivors 1 to 14 Years After Radiation Therapy

International Nuclear Information System (INIS)

Pettersson, Niclas; Olsson, Caroline; Tucker, Susan L.; Alsadius, David; Wilderäng, Ulrica; Johansson, Karl-Axel; Steineck, Gunnar

2013-01-01

Purpose: To investigate how treatment-related and non-treatment-related factors impact urethral pain among long-term prostate cancer survivors. Methods and Materials: Men treated for prostate cancer with radiation therapy at the Sahlgrenska University Hospital in Göteborg, Sweden from 1993 to 2006 were approached with a study-specific postal questionnaire addressing symptoms after treatment, including urethral burning pain during urination (n=985). The men had received primary or salvage external-beam radiation therapy (EBRT) or EBRT in combination with brachytherapy (BT). Prescribed doses were commonly 70 Gy in 2.0-Gy fractions for primary and salvage EBRT and 50 Gy plus 2 × 10.0 Gy for EBRT + BT. Prostatic urethral doses were assessed from treatment records. We also recruited 350 non-pelvic-irradiated, population-based controls matched for age and residency to provide symptom background rates. Results: Of the treated men, 16% (137 of 863) reported urethral pain, compared with 11% (27 of 242) of the controls. The median time to follow-up was 5.2 years (range, 1.1-14.3 years). Prostatic urethral doses were similar to prescription doses for EBRT and 100% to 115% for BT. Fractionation-corrected dose and time to follow-up affected the occurrence of the symptom. For a follow-up ≥3 years, 19% of men (52 of 268) within the 70-Gy EBRT + BT group reported pain, compared with 10% of men (23 of 222) treated with 70 Gy primary EBRT (prevalence ratio 1.9; 95% confidence interval 1.2-3.0). Of the men treated with salvage EBRT, 10% (20 of 197) reported urethral pain. Conclusions: Survivors treated with EBRT + BT had a higher risk for urethral pain compared with those treated with EBRT. The symptom prevalence decreased with longer time to follow-up. We found a relationship between fractionation-corrected urethral dose and pain. Among long-term prostate cancer survivors, the occurrence of pain was not increased above the background rate for prostatic urethral doses up to 70 Gy

Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

DEFF Research Database (Denmark)

Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

2015-01-01

BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non......-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised...... disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised...

Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer

DEFF Research Database (Denmark)

Denmeade, Samuel R; Jakobsen, Carsten M; Janssen, Samuel

2003-01-01

Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective...... against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells....

Effects of occupational therapy on quality of life of patients with metastatic prostate cancer

OpenAIRE

Huri, Meral; Huri, Emre; Kayihan, Hulya; Altuntas, Onur

2015-01-01

Objectives: To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC). Methods: Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, H...

Castration resistant prostate cancer in the year 2013

International Nuclear Information System (INIS)

Marencak, J.

2013-01-01

Prostate cancer (PC) is the most frequent solid neoplasm in Europe and therefore is regarded as one of the major medical problems of the male population. PC is extremely complicated and interindividual different tumor. The method of treatment depends on several factors, but mainly on the stage of prostate cancer. The term Hormone resistant (refractory) prostate cancer (HRPC) was used in older terminology. HRPC is cancer that progresses despite castrate levels of testosterone achieved androgen deprivation therapy (ADT), which is resistant to any hormonal therapy. Currently is increasingly used (instead of name HRPC) name CRPC – so called PC resistant for castration (CRPC – castration resistant prostate cancer), which is still able to respond to certain hormonal manipulation, although it meets the the criteria for HRPC. Objectives of article: provide information to the general medical community (and especially urologists and oncologists) mainly about a treatment of complicated issues of CRPC. The basic data on the current and future. The article presented basic data on the current and future possibilities of such therapy and increasing basic knowledge about treating CRPC should improve the care of patients with advanced PC. (author)

Evaluation of Online/Offline Image Guidance/Adaptation Approaches for Prostate Cancer Radiation Therapy

International Nuclear Information System (INIS)

Qin, An; Sun, Ying; Liang, Jian; Yan, Di

2015-01-01

Purpose: To evaluate online/offline image-guided/adaptive treatment techniques for prostate cancer radiation therapy with daily cone-beam CT (CBCT) imaging. Methods and Materials: Three treatment techniques were evaluated retrospectively using daily pre- and posttreatment CBCT images on 22 prostate cancer patients. Prostate, seminal vesicles (SV), rectal wall, and bladder were delineated on all CBCT images. For each patient, a pretreatment intensity modulated radiation therapy plan with clinical target volume (CTV) = prostate + SV and planning target volume (PTV) = CTV + 3 mm was created. The 3 treatment techniques were as follows: (1) Daily Correction: The pretreatment intensity modulated radiation therapy plan was delivered after online CBCT imaging, and position correction; (2) Online Planning: Daily online inverse plans with 3-mm CTV-to-PTV margin were created using online CBCT images, and delivered; and (3) Hybrid Adaption: Daily Correction plus an offline adaptive inverse planning performed after the first week of treatment. The adaptive plan was delivered for all remaining 15 fractions. Treatment dose for each technique was constructed using the daily posttreatment CBCT images via deformable image registration. Evaluation was performed using treatment dose distribution in target and critical organs. Results: Treatment equivalent uniform dose (EUD) for the CTV was within [85.6%, 100.8%] of the pretreatment planned target EUD for Daily Correction; [98.7%, 103.0%] for Online Planning; and [99.2%, 103.4%] for Hybrid Adaptation. Eighteen percent of the 22 patients in Daily Correction had a target dose deficiency >5%. For rectal wall, the mean ± SD of the normalized EUD was 102.6% ± 2.7% for Daily Correction, 99.9% ± 2.5% for Online Planning, and 100.6% ± 2.1% for Hybrid Adaptation. The mean ± SD of the normalized bladder EUD was 108.7% ± 8.2% for Daily Correction, 92.7% ± 8.6% for Online Planning, and 89.4% ± 10.8% for Hybrid

Combinatorial strategy of epigenetic and hormonal therapies: A novel promising approach for treating advanced prostate cancer.

Science.gov (United States)

Motawi, Tarek K; Darwish, Hebatallah A; Diab, Iman; Helmy, Maged W; Noureldin, Mohamed H

2018-04-01

Estrogens act as key factors in prostate biology, cellular proliferation and differentiation as well as cancer development and progression. The expression of estrogen receptor (ER)-β appears to be lost during prostate cancer progression through hypermethylation mechanism. Epigenetic drugs such as 5-aza-2'-deoxycytidine (5-AZAC) and Trichostatin A (TSA) showed efficacy in restoring ERβ expression in prostate cancer cells. This study was designed to explore the potential anti-carcinogenic effects resulting from re-expressing ERβ1 using 5-AZAC and/or TSA, followed by its stimulation with Diarylpropionitrile (DPN), a selective ERβ1 agonist, in prostate cancer cell line PC-3. Cells were treated with 5-AZAC, TSA, DPN and their combination. Subsequently, they were subjected to proliferation assays, determinations of ERβ1 expression, protein levels of active caspase-3, cyclin D1, β-catenin and VEGF. Treatment with these drugs exhibited an increase in ERβ1 expression to different extents as well as active caspase-3 levels. Meanwhile, a significant reduction in cyclin D1, VEGF and β-catenin levels was achieved as compared to the vehicle control group (p epigenetic and hormonal therapies may be beneficial in treating advanced prostate cancer. Copyright © 2018. Published by Elsevier Inc.

The Role of MRI in Prostate Cancer Active Surveillance

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Linda M. Johnson

2014-01-01

Full Text Available Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance.

Time to second prostate specific antigen (PSA) failure is a surrogate endpoint for prostate cancer death in prospective trials of therapy for localized disease

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Zietman, A L; Dallow, K C; Shipley, W U; Heney, N M; McManus, P L

1995-07-01

Purpose In assessing the efficacy of the competing curative therapies for prostate cancer the most relevant endpoint is cancer specific death. Due to the long natural history of the disease and the use of salvage androgen suppression prospective trials need to mature for at least a decade to provide meaningful results. An endpoint that predicted for cancer death with high probability would allow more rapid completion of prospective studies, hopefully before the tested therapies become outdated. Materials and methods 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer between 1982 and 1992 were evaluated. All received radical irradiation to either a standard dose of 67.2Gy or a higher dose of 75.6Gy (the latter employing a proton beam boost). 76 men have received androgen suppression or orchiectomy for salvage following relapse (median follow-up 6.9 years). Of this group 35 experienced a second relapse heralded by a rise in the serum PSA. Second failure was scored on the date that the serum PSA rose to greater than 10% above the post-androgen suppression nadir. Kaplan-Meier analysis was made of survival from the time of second PSA failure and the cause of death established in all patients who subsequently died. Results The median duration of response to hormone therapy following first failure was 27.2 months. The actuarial survival from the time of second biochemical relapse was 93%, 66%, 35%, and 0% at 1, 2, 3, and 4 years respectively (50% at 32 months). 16 patients have so far died after second failure all from causes related to their prostate cancer. Conclusion Second PSA failure appears to be a secure surrogate for impending prostate cancer death. Its use as an endpoint in prospective studies should allow earlier reporting by 2 - 3 years.

Efficacy of walking exercise in promoting cognitive-psychosocial functions in men with prostate cancer receiving androgen deprivation therapy

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Lee C

2012-07-01

Full Text Available Abstract Background Prostate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT. Methods A 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale. Discussion The significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately

Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

Science.gov (United States)

Soekmadji, Carolina; Corcoran, Niall M; Oleinikova, Irina; Jovanovic, Lidija; Ramm, Grant A; Nelson, Colleen C; Jenster, Guido; Russell, Pamela J

2017-10-01

The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation. © 2017 Wiley Periodicals, Inc.

Neuroendocrine differentiation in prostate cancer – a review

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R. Popescu

2015-12-01

Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

Intermittent hormonal therapy in the treatment of post-irradiation residual/recurrent prostate cancer

International Nuclear Information System (INIS)

Williams, Aaron O; Kocherill, Paul G; Wallace, Michelle; Forman, Jeffrey D

1996-01-01

Purpose: To evaluate the efficacy and toxicity of intermittent hormonal therapy in the treatment of residual/recurrent prostate cancer. Materials and Methods: Seventeen patients with biochemical evidence of residual/recurrent prostate cancer were initially treated with radiation therapy (RT)(13), neo-adjuvant hormonal therapy and RT (3), or RT following prostatectomy (1). The mean follow-up time was 19.4 months from the initiation of hormonal therapy. Hormonal therapy consisted of an LH-RH agonist alone (7), an anti-androgen alone (1) or a combination of both (9). Hormonal therapy was continued until the prostatic specific antigen (PSA) level became undetectable. IHT was reinstituted when the PSA reached a pre-determined level, usually greater than or equal to 10ng/ml. Results: The mean time from completion of primary treatment to the initiation of hormonal therapy was 32.5 months. The mean PSA at the start of the first cycle of hormonal therapy was 43.9ng/ml, the second cycle, 11.9ng/ml and the third cycle, 24ng/ml. The mean PSA levels at the end of the first and second cycle of hormonal therapy were .48 and .42ng/ml, respectively. No patient has yet completed the third cycle of hormonal therapy. The average duration of hormonal therapy was 10 months for the first cycle and 4 months for the second cycle. The mean intermittent time off hormones were 9.3 months between cycles 1 and 2, and 10 months between cycles 2 and 3. No patient has yet become refractory to hormonal therapy. Currently all patients are alive. All patients experienced hot flashes and decreased libido at varying degrees during treatment. Thirty-five percent experienced gynecomastia. During the intervals between hormonal therapy, most patients reported a decrease in hot flashes. Conclusion: This analysis supplies preliminary evidence that intermittent hormonal therapy is a viable option in patients with biochemical evidence of disease following initial therapy. It is associated with less treatment

Prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

1987-01-01

This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

Prostate cancer

International Nuclear Information System (INIS)

Murphy, G.P.; Kuss, R.; Khoury, S.; Chatelain, C.; Denis, L.

1987-01-01

This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results

Osteoporosis and prostate cancer

DEFF Research Database (Denmark)

Poulsen, Mads Hvid; Nielsen, Morten Frost Munk; Abrahamsen, Bo

2014-01-01

Abstract Objective. The aim of this study was to analyse the prevalence of osteoporosis and risk factors of osteoporotic fractures before androgen deprivation in Danish men. Treatment and prognosis of prostate cancer necessitate management of long-term consequences of androgen deprivation therapy...... (ADT), including accelerated bone loss resulting in osteoporosis. Osteoporotic fractures are associated with excess morbidity and mortality. Material and methods. Patients with prostate cancer awaiting initiation of ADT were consecutively included. Half of the patients had localized disease and were...... level was 30.5 g/l (1-5714 g/l). The average Gleason score was 7.8 (range 5-10, SD 1.1). Fifty patients had localized prostate cancer and the other 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% before ADT. There was no significant...

Low-dose irradiation for controlling prostate cancer

International Nuclear Information System (INIS)

Cuttler, J.M.

2003-01-01

Prostate cancer is the second most commonly diagnosed cancer among North American men and the second leading cause of death in those aged 65 and over. The American Cancer Society recommends testing those over age 50 who are expected to live at least 10 years, even though the ability of early detection to decrease prostate cancer mortality has not been demonstrated. So controversy exists about the appropriateness of screening because of the considerable economic and social burden of diagnosing and treating prostate cancer, coupled with the projected large increase in the number of new cases as the population ages. This very important public health issue could be addressed at low cost by total-body low-dose irradiation therapy to stimulate the patient's own defences to prevent and control most cancers, including prostate cancer, with no symptomatic side effects. (author)

Immune Response to Sipuleucel-T in Prostate Cancer

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David I. Quinn

2012-04-01

Full Text Available Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients’ own antigen presenting cells (APCs to prostatic acid phosphatase (PAP fused with granulocyte-macrophage colony stimulating factor (GM-CSF and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The

Internet-Based Education for Prostate Cancer Screening

Science.gov (United States)

2007-12-01

cells. n Hormone therapy: Certain hormones are given or removed. This helps to keep cancer cells from growing. n Cryotherapy : A special probe is placed...are many other diseases that are more deadly than prostate cancer . Talk to your doctor about how to prevent them. n As a result, most men with...prostate cancer ranks 5th, behind heart disease, lung cancer , stroke, and emphysema. Centers for Disease Control and Prevention , National Canter for Health

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

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Ju Andrew W

2013-01-01

Full Text Available Abstract Background Hypofractionated stereotactic body radiation therapy (SBRT has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Methods Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL measures were assessed at baseline and follow-up. Results All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. Conclusions In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. Trial registration The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510.

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

International Nuclear Information System (INIS)

Ju, Andrew W; Lei, Siyuan; Suy, Simeng; Lynch, John H; Dritschilo, Anatoly; Collins, Sean P; Wang, Hongkun; Oermann, Eric K; Sherer, Benjamin A; Uhm, Sunghae; Chen, Viola J; Pendharkar, Arjun V; Hanscom, Heather N; Kim, Joy S

2013-01-01

Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510)

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

International Nuclear Information System (INIS)

Rucinski, Antoni; Brons, Stephan; Richter, Daniel; Habl, Gregor; Debus, Jürgen; Bert, Christoph; Haberer, Thomas; Jäkel, Oliver

2015-01-01

Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90 Rectum ), respectively. The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90 Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal

Cardiovascular risk during hormonal treatment in patients with prostate cancer

International Nuclear Information System (INIS)

Van Poppel, Hein; Tombal, Bertrand

2011-01-01

The objective of this review is to provide information on cardiovascular risk following androgen-deprivation therapy (ADT) in prostate cancer patients and to suggest potential prevention and management strategies. Androgen deprivation therapy can cause peripheral insulin resistance, increase fat mass and low-density lipoprotein cholesterol, and induce type 2 diabetes. While recent studies have reported an association in patients with prostate cancer between ADT and increased risk of cardiovascular events, other studies have not detected the association. However, at this time, it is plausible that ADT could increase cardiovascular risk because of the adverse effect of ADT on risk factors for cardiovascular disease. It is advisable that prostate cancer patients in whom ADT is initiated be referred to their physician, who will carefully monitor them for potential metabolic effects. Therefore, physicians should be informed about these potential side effects. This especially applies to men aged >65 years and those with pre-existing cardiovascular comorbidities. Adopting a healthy lifestyle including a balanced diet and regular physical activity is recommended. Patients with cardiovascular disease should receive appropriate preventive therapies, including lipid-lowering, antihypertensive, glucose-lowering, and antiplatelet therapy. ADT should preferably not be unnecessarily administered to prostate cancer patients with pre-existing cardiovascular disease, certainly not to those in whom the risk of prostate cancer-specific mortality is low. The physician should carefully weigh the potential benefits of ADT against the possible risks in individual patients with prostate cancer

Changes in Initial Treatment for Prostate Cancer Among Medicare Beneficiaries, 1999–2007

International Nuclear Information System (INIS)

Dinan, Michaela A.; Robinson, Timothy J.; Zagar, Timothy M.; Scales, Charles D.; Curtis, Lesley H.; Reed, Shelby D.; Lee, W. Robert; Schulman, Kevin A.

2012-01-01

Purpose: In the absence of evidence from large clinical trials, optimal therapy for localized prostate cancer remains unclear; however, treatment patterns continue to change. We examined changes in the management of patients with prostate cancer in the Medicare population. Methods and Materials: We conducted a retrospective claims-based analysis of the use of radiation therapy, surgery, and androgen deprivation therapy in the 12 months after diagnosis of prostate cancer in a nationally representative 5% sample of Medicare claims. Patients were Medicare beneficiaries 67 years or older with incident prostate cancer diagnosed between 1999 and 2007. Results: There were 20,918 incident cases of prostate cancer between 1999 and 2007. The proportion of patients receiving androgen deprivation therapy decreased from 55% to 36%, and the proportion of patients receiving no active therapy increased from 16% to 23%. Intensity-modulated radiation therapy replaced three-dimensional conformal radiation therapy as the most common method of radiation therapy, accounting for 77% of external beam radiotherapy by 2007. Minimally invasive radical prostatectomy began to replace open surgical approaches, being used in 49% of radical prostatectomies by 2007. Conclusions: Between 2002 and 2007, the use of androgen deprivation therapy decreased, open surgical approaches were largely replaced by minimally invasive radical prostatectomy, and intensity-modulated radiation therapy replaced three-dimensional conformal radiation therapy as the predominant method of radiation therapy in the Medicare population. The aging of the population and the increasing use of newer, higher-cost technologies in the treatment of patients with prostate cancer may have important implications for nationwide health care costs.

Genomic rearrangements of PTEN in prostate cancer

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Sopheap ePhin

2013-09-01

Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

Urethrogram-directed Stereotactic Body Radiation Therapy (SBRT for Clinically Localized Prostate Cancer in Patients with Contraindications to Magnetic Resonance Imaging

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Ima ePaydar

2015-09-01

Full Text Available Purpose: Magnetic resonance imaging (MRI-directed stereotactic body radiation therapy (SBRT has been established as a safe and effective treatment for prostate cancer. For patients with contraindications to MRI, CT-urethrogram is an alternative imaging approach to identify the location of the prostatic apex to guide treatment. This study sought to evaluate the safety of urethrogram-directed SBRT for prostate cancer.Methods: Between February 2009 and January 2014, 31 men with clinically localized prostate cancer were treated definitively with urethrogram-directed SBRT with or without supplemental intensity modulated radiation therapy (IMRT at Georgetown University Hospital. SBRT was delivered either as a primary treatment of 35-36.25 Gray (Gy in 5 fractions or as a boost of 19.5 Gy in 3 fractions followed by supplemental conventionally fractionated intensity modulated radiation therapy (45-50.4 Gy. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0.Results: The median patient age was 70 years with a median prostate volume of 38 cc. The median follow-up was 3.7 years. The patients were elderly (Median age = 70, and comorbidities were common (Carlson Comorbidity Index > 2 in 36%. 71% of patients utilized alpha agonists prior to treatment, and 9.7% had prior procedures for benign prostatic hyperplasia (BPH. The 3-year actuarial incidence rates of > Grade 3 GU toxicity and > Grade 2 GI toxicity were 3.2% and 9.7%, respectively. There were no Grade 4 or 5 toxicities.Conclusions: MRI is the preferred imaging modality to guide prostate SBRT treatment. However, urethrogram-directed SBRT is a safe alternative for the treatment of patients with prostate cancer who are unable to undergo MRI.

Effects of occupational therapy on quality of life of patients with metastatic prostate cancer

Science.gov (United States)

Huri, Meral; Huri, Emre; Kayihan, Hulya; Altuntas, Onur

2015-01-01

Objectives: To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC). Methods: Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey. The Canadian Occupational Performance Measure (COPM) was used to measure the occupational performance and identify difficulties in daily living activities. The QoL and symptom status were measured by The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 and its Prostate Cancer Module. A 12-week OT-CBSM intervention including client-centered training of daily living activities, recreational group activities, and cognitive behavioral stress management intervention were applied. Results: The COPM performance and satisfaction scores, which indicate occupational participation and QoL increased statistically in the treatment group in relation to men who were included in the home-program (p≤0.05). Conclusion: A 12-week OT-CBSM intervention was effective in improving QoL in men treated for MPC, and these changes were associated significantly with occupational performance. PMID:26219446

Multiparametric prostate MRI for follow-up monitoring after radiation therapy

International Nuclear Information System (INIS)

Weidner, A.M.; Dinter, D.J.; Bohrer, M.; Sertdemir, M.; Hausmann, D.; Wenz, F.; Schoenberg, S.O.

2012-01-01

Radiation therapy is a therapeutic option with curative intent for patients with prostate cancer. Monitoring of prostate-specific antigen (PSA) values is the current standard of care in the follow-up. Imaging is recommended only for symptomatic patients and/or for further therapeutic options. For detection of local recurrence magnetic resonance imaging (MRI) of the prostate is acknowledged as the method of choice. Good results for primary diagnosis were found especially in combination with functional techniques, whereas in recurrent prostate cancer only few studies with heterogeneous study design are available for prostate MRI. Furthermore, changes in different MRI modalities due to radiation therapy have been insufficiently investigated to date. As the initial results were promising prostate MRI and available therapeutic options for detection of local recurrence should be considered in patients with increased PSA. (orig.) [de

Focal therapy with high-intensity focused ultrasound for prostate cancer in the elderly: a feasibility study with 10 years follow-up

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Amine B. El Fegoun

2011-04-01

Full Text Available PURPOSE: To evaluate the long-term efficacy of prostate cancer control and complication rates, in the elderly, after focal therapy with high-intensity focused ultrasound (HIFU. MATERIALS AND METHODS: Between June 1997 and March 2000, patients with localized prostate cancer were included into a focal therapy protocol. Inclusion criteria were: PSA < 10 ng/mL, < 3 positive biopsies with only 1 lobe involved, clinical stage < T2a, Gleason score < 7 (3+4, negative CT scan and bone scan. Hemi-ablation of the prostate was performed with the Ablatherm(R device. Survival, complication rates and urinary continence were evaluated. Control biopsies were performed at 1 year. Treatment failure was defined as a positive biopsy or need for salvage therapy. RESULTS: Twelve patients with a mean age 70 years were included. Median follow-up was 10 years. Control prostate biopsies were negative in 11/12 (91% patients. Overall survival was 83% (10/12 and cancer specific survival was 100% at 10 years. Two patients died from other causes. Recurrence free survival was 90% (95% CI; 0.71-1 at 5 years, and 38% (95% CI; 0.04-0.73 at 10 years. Five patients had salvage therapy with repeat HIFU (n = 1 or hormonal therapy (n = 4 and all salvage patients were alive at 10 years. No patients developed lymph node or bone metastasis. No patients suffered from urinary incontinence. International Prostate Symptom Score was stable at 1 year. Complications included two urinary tract infections and one episode of acute urinary retention. CONCLUSIONS: Hemi-prostate ablation with HIFU can be safely performed in selected elderly patients with adequate long-term cancer control and low complication rates. Results from larger prospective studies using improved imaging techniques and extensive biopsy protocols are awaited.

Monotherapy of androgen deprivation therapy versus radical prostatectomy among veterans with localized prostate cancer: comparative effectiveness analysis of retrospective cohorts

Directory of Open Access Journals (Sweden)

Liu J

2012-05-01

Full Text Available Jinan Liu1,2, Lizheng Shi1,2,3, Oliver Sartor31Tulane University, School of Public Health and Tropical Medicine, 2Southeast Louisiana Veterans Health Care System, Tulane University, 3School of Medicine and Tulane Cancer Center, New Orleans, LA, USABackground: This retrospective cohort study aimed to examine the comparative effectiveness of monotherapy of primary androgen deprivation therapy or radical prostatectomy.Methods: Male patients with localized prostate cancer (T1-T2, N0, M0 were identified in the Veterans Affairs Veterans Integrated Service Network 16 data warehouse (January 2003 to June 2006, with one-year baseline and at least three-year follow-up data (until June 2009. Patients were required to be 18–75 years old and without other recorded cancer history. The initiation of primary androgen deprivation therapy or monotherapy of radical prostatectomy within six months after the first diagnosis of prostate cancer was used as the index date. Primary androgen deprivation therapy patients were matched to the radical prostatectomy patients via propensity score, which was predicted from a logistic regression of treatment selection (primary androgen deprivation therapy versus radical prostatectomy on age, race, marital status, insurance type, cancer stage, Charlson comorbidity index, and alcohol and tobacco use. The overall survival from initiation of index treatment was then analyzed using the Kaplan–Meier and Cox proportional hazards model.Results: The two cohorts were well matched at baseline (all P > 0.05. During a median follow-up of 4.3 years, the cumulative incidence of death was 13 (10.57% among 123 primary androgen deprivation therapy patients and four (3.25% among 123 radical prostatectomy patients (P < 0.05. The overall three-year survival rate was 92.68% for primary androgen deprivation therapy and 98.37% for radical prostatectomy (P < 0.05. Patients who received primary androgen deprivation therapy had almost three times as

Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism.

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Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

2015-12-04

Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed.

Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients

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Bernardino Clavo

2015-01-01

Full Text Available Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n=12 previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83% patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52–119. Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p<0.001 and the number of endoscopy treatments from 37 to 4 (p=0.032. Hemoglobin levels changed from 11.1 (7–14 g/dL to 13 (10–15 g/dL, before and after ozone therapy, respectively (p=0.008. Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation.

Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy

DEFF Research Database (Denmark)

Hvid, Thine; Winding, Kamilla; Rinnov, Anders

2013-01-01

Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine me...... and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P...

Prostate-Specific Membrane Antigen Targeted Therapy of Prostate Cancer Using a DUPA-Paclitaxel Conjugate.

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Lv, Qingzhi; Yang, Jincheng; Zhang, Ruoshi; Yang, Zimeng; Yang, Zhengtao; Wang, Yongjun; Xu, Youjun; He, Zhonggui

2018-05-07

Prostate cancer (PCa) is the most prevalent cancer among men in the United States and remains the second-leading cause of cancer mortality in men. Paclitaxel (PTX) is the first line chemotherapy for PCa treatment, but its therapeutic efficacy is greatly restricted by the nonspecific distribution in vivo. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most PCa cells, and its expression level increases with cancer aggressiveness, while being present at low levels in normal cells. The high expression level of PSMA in PCa cells offers an opportunity for target delivery of nonspecific cytotoxic drugs to PCa cells, thus improving therapeutic efficacy and reducing toxicity. PSMA has high affinity for DUPA, a glutamate urea ligand. Herein, a novel DUPA-PTX conjugate is developed using DUPA as the targeting ligand to deliver PTX specifically for treatment of PSMA expressing PCa. The targeting ligand DUPA enhances the transport capability and selectivity of PTX to tumor cells via PSMA mediated endocytosis. Besides, DUPA is conjugated with PTX via a disulfide bond, which facilitates the rapid and differential drug release in tumor cells. The DUPA-PTX conjugate exhibits potent cytotoxicity in PSMA expressing cell lines and induces a complete cessation of tumor growth with no obvious toxicity. Our findings give new insight into the PSMA-targeted delivery of chemotherapeutics and provide an opportunity for the development of novel active targeting drug delivery systems for PCa therapy.

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy

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Vito Cucchiara

2017-01-01

Full Text Available Androgen receptor (AR signaling remains the major oncogenic pathway in prostate cancer (PCa. Androgen-deprivation therapy (ADT is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC. Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles involved in AR expression and their possible role as therapeutic targets.

Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study.

Science.gov (United States)

Abedinpour, Parisa; Baron, Véronique T; Chrastina, Adrian; Rondeau, Gaelle; Pelayo, Jennifer; Welsh, John; Borgström, Per

2017-12-01

Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use. Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin. Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR. Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice. © 2017 Wiley Periodicals, Inc.

Atmospheric Pressure Photoionization Tandem Mass Spectrometry of Androgens in Prostate Cancer

Science.gov (United States)

Lih, Fred Bjørn; Titus, Mark A.; Mohler, James L.; Tomer, Kenneth B.

2010-01-01

Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-α-androstanedione required detection of a novel parent ion, [M + 15]+. The nature of this parent ion was explored and the method applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization. PMID:20560527

What Aspects of Personal Care Are Most Important to Patients Undergoing Radiation Therapy for Prostate Cancer?

International Nuclear Information System (INIS)

Foley, Kimberley A.; Feldman-Stewart, Deb; Groome, Patti A.; Brundage, Michael D.; McArdle, Siobhan; Wallace, David; Peng, Yingwei; Mackillop, William J.

2016-01-01

Purpose/Objective: The overall quality of patient care is a function of the quality of both its technical and its nontechnical components. The purpose of this study was to identify the elements of nontechnical (personal) care that are most important to patients undergoing radiation therapy for prostate cancer. Methods and Materials: We reviewed the literature and interviewed patients and health professionals to identify elements of personal care pertinent to patients undergoing radiation therapy for prostate cancer. We identified 143 individual elements relating to 10 aspects of personal care. Patients undergoing radical radiation therapy for prostate cancer completed a self-administered questionnaire in which they rated the importance of each element. The overall importance of each element was measured by the percentage of respondents who rated it as “very important.” The importance of each aspect of personal care was measured by the mean importance of its elements. Results: One hundred eight patients completed the questionnaire. The percentage of patients who rated each element “very important” ranged from 7% to 95% (mean 61%). The mean importance rating of the elements of each aspect of care varied significantly: “perceived competence of caregivers,” 80%; “empathy and respectfulness of caregivers,” 67%; “adequacy of information sharing,” 67%; “patient centeredness,” 59%; “accessibility of caregivers,” 57%; “continuity of care,” 51%; “privacy,” 51%; “convenience,” 45%; “comprehensiveness of services,” 44%; and “treatment environment,” 30% (P<.0001). Neither age nor education was associated with importance ratings, but the patient's health status was associated with the rating of some elements of care. Conclusions: Many different elements of personal care are important to patients undergoing radiation therapy for prostate cancer, but the 3 aspects of care that most believe are most important are these: the perceived

What Aspects of Personal Care Are Most Important to Patients Undergoing Radiation Therapy for Prostate Cancer?

Energy Technology Data Exchange (ETDEWEB)

Foley, Kimberley A. [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Feldman-Stewart, Deb [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Groome, Patti A. [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Brundage, Michael D. [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Cancer Centre of Southeastern Ontario, Kingston, Ontario (Canada); McArdle, Siobhan [Cancer Centre of Southeastern Ontario, Kingston, Ontario (Canada); Wallace, David [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Peng, Yingwei [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Department of Mathematics and Statistics, Queen' s University, Kingston, Ontario (Canada); Mackillop, William J., E-mail: William.mackillop@krcc.on.ca [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Cancer Centre of Southeastern Ontario, Kingston, Ontario (Canada)

2016-02-01

Purpose/Objective: The overall quality of patient care is a function of the quality of both its technical and its nontechnical components. The purpose of this study was to identify the elements of nontechnical (personal) care that are most important to patients undergoing radiation therapy for prostate cancer. Methods and Materials: We reviewed the literature and interviewed patients and health professionals to identify elements of personal care pertinent to patients undergoing radiation therapy for prostate cancer. We identified 143 individual elements relating to 10 aspects of personal care. Patients undergoing radical radiation therapy for prostate cancer completed a self-administered questionnaire in which they rated the importance of each element. The overall importance of each element was measured by the percentage of respondents who rated it as “very important.” The importance of each aspect of personal care was measured by the mean importance of its elements. Results: One hundred eight patients completed the questionnaire. The percentage of patients who rated each element “very important” ranged from 7% to 95% (mean 61%). The mean importance rating of the elements of each aspect of care varied significantly: “perceived competence of caregivers,” 80%; “empathy and respectfulness of caregivers,” 67%; “adequacy of information sharing,” 67%; “patient centeredness,” 59%; “accessibility of caregivers,” 57%; “continuity of care,” 51%; “privacy,” 51%; “convenience,” 45%; “comprehensiveness of services,” 44%; and “treatment environment,” 30% (P<.0001). Neither age nor education was associated with importance ratings, but the patient's health status was associated with the rating of some elements of care. Conclusions: Many different elements of personal care are important to patients undergoing radiation therapy for prostate cancer, but the 3 aspects of care that most believe are most important are these: the

The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer

International Nuclear Information System (INIS)

Ritter, Mark A.; Gilchrist, Kennedy W.; Voytovich, Marta; Chappell, Richard J.; Verhoven, Bret M.

2002-01-01

Purpose: Some prostate cancers may have molecular alterations that render them less responsive to radiation therapy; identification of these alterations before treatment might allow improved treatment optimization. This study investigated whether p53, a potential molecular determinant, could predict long-term radiation therapy outcome in a restricted group of relatively favorable-risk prostate cancer patients treated uniformly with irradiation alone. Methods and Materials: This study included 53 patients previously treated with radiotherapy for favorable-to-intermediate-risk prostate cancer. These patients were selected for relatively low pretreatment PSAs (≤21 ng/mL) and Gleason scores (≤7) to decrease the likelihood of nonlocalized disease, because disease localization was necessary to examine the efficacy of localized radiation therapy. The status of p53 was immunohistochemically assessed in paraffin-embedded pretreatment biopsy specimens, along with appropriate controls. This marker was selected based upon a usable mutation prevalence in early-stage prostate cancer and its potential linkage with radiation response via cell cycle, DNA repair, and cell death pathways. Correlation between p53 mutation and clinical outcome was analyzed in univariate and multivariate fashion and included conventional prognosticators, such as stage, grade, and PSA. Freedom from biochemical failure was determined using American Society for Therapeutic Radiology and Oncology criteria. Limitations of prior studies were potentially avoided by requiring adequate posttreatment follow-up (median follow-up in nonfailing patients of 5.1 years), as well as pretreatment PSA and Gleason scores that suggested localized disease, and uniformity of treatment. Results: The total group of 53 favorable-to-intermediate-risk patients demonstrated an actuarial biochemical failure rate of 35% at 5 years. Forty percent of all specimens had a greater than 10% labeling index for p53 mutation, and

Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

OpenAIRE

Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

2015-01-01

Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 pa...

Prostate cancer

International Nuclear Information System (INIS)

Bey, P.; Beckendorf, V.; Stines, J.

2001-01-01

Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extra-capsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk. (authors)

Prospective study of exercise intervention in prostate cancer patients on androgen deprivation therapy

International Nuclear Information System (INIS)

Beydoun, Nadine; Bucci, Joseph A.; Chin, Yaw S.; Spry, Nigel; Newton, Robert; Galvão, Daniel A.

2014-01-01

Androgen deprivation therapy (ADT) is an important component of modern prostate cancer treatment. Survival benefits from neo-adjuvant and adjuvant hormones may take years to manifest, and balancing this with potential morbidity of therapy can be challenging. This study aimed to assess whether education and short-term combined aerobic and resistance exercises could help to ameliorate the adverse side effects of ADT. Eight hundred fifty-nine patients with relapsed or metastatic prostate cancer on leuprorelin acetate were allocated to three interventional streams based on patient preference and medical fitness: supervised group (Face-to-Face) exercise sessions, home-based (At Home) exercise or a support programme for those incapable of exercising (Support). Patients enrolled onto Face to Face underwent measurement of body composition and cardiorespiratory fitness variables at baseline and programme completion. Patients in the exercise streams were surveyed to determine the programme's impact on physical fitness and well-being. Statistically significant improvements (p<0.001) were seen in all measured cardiorespiratory fitness and strength variables. Programme attrition rates were low (75/859; 8.7%), the primary reason for withdrawal being discontinuation of hormones (70%). Programme satisfaction was high, with 98% of surveyed patients reporting a positive impact on fitness and 97% planning to continue exercising after programme completion. At 6 months, improved physical and emotional well-being was reported by 93 and 79% of patients, respectively. A short-term structured exercise intervention results in high compliance and significant improvements in muscle strength and cardiorespiratory fitness in prostate cancer patients on ADT.

The survival analysis on localized prostate cancer treated with neoadjuvant endocrine therapy followed by intensity modulated radiation therapy

International Nuclear Information System (INIS)

Gao Hong; Li Gaofeng; Wu Qinhong; Li Xuenan; Zhong Qiuzi; Xu Yonggang

2010-01-01

Objective: To retrospectively investigate clinical outcomes and prognostic factors in localized prostate cancer treated with neoadjuvant endocrine therapy followed by intensity modulated radiotherapy (IMRT). Methods: Between March 2003 and October 2008, 54 localized prostate cancer treated by IMRT were recruited. All patients had received endocrine therapy before IMRT. The endocrine therapy included surgical castration or medical castration in combination with antiandrogens. The target of IMRT was the prostate and seminal vesicles with or without pelvis. The biochemical failure was defined according to the phoenix definition. By using the risk grouping standard proposed by D'Amico, patients were divided into three groups: low-risk group (n = 5), intermediate-risk group (n = 12), and high-risk group (n = 37). Kaplan-Meier method was used to calculate the overall survival rate. Prognostic factors were analyzed by univariate and multiple Cox regression analysis. Results: The follow-up rate was 98%. The number of patients under follow-up was 39 at 3 years and 25 at 5 years. Potential prognostic factors, including risk groups, mode of endocrine therapy, time of endocrine therapy, phoenix grouping before IMRT, the prostate specific antigen doubling time (PSADT) before radiotherapy, PSA value before IMRT, interval of endocrine therapy and IMRT, irradiation region, and irradiation dose were analyzed by survival analysis. In univariate analysis, time of endocrine therapy (75 % vs 95 %, χ 2 = 6. 45, P = 0. 011), phoenix grouping before IMRT (87% vs 96%, χ 2 = 4. 36, P = 0. 037), interval of endocrine therapy and IMRT (80% vs 95%, χ 2 = 11.60, P= 0. 001), irradiation dose (75% vs 91%, χ 2 =5.92, P= 0. 015) were statistically significant prognostic factors for 3 - year overall survival , and risk groups (85 vs 53 vs 29, χ 2 = 6. 40, P =0. 041) and PSADT before IMRT (62 vs 120, U =24. 50, P =0. 003) were significant factors for the median survival time. In the multiple Cox

Androgen deprivation therapy and cardiovascular risk in patients with prostate cancer

International Nuclear Information System (INIS)

Khan, M.Y.; Haider, N.; Rasul, S.; Mahmood, A.; Nadeem, M.S.

2017-01-01

The objective of this study was to investigate the effects of androgen deprivation therapy (ADT) on risk of subsequent cardiovascular morbidity in men with prostate cancer. Study Design: Quasi experimental study. Place and Duration of Study: Department of oncology Combined Military Hospital Rawalpindi, from Sep 2014 to May 2015. Patients and Methods: Thirty consecutive patients fulfilling inclusion criteria were enrolled. All patients were subjected to medical castration/ androgen deprivation therapy (ADT) with monthly 3.75 mg leuprorelin acetate intramuscular injection until castrate levels of testosterone (<50ng/dL) were achieved. We used Framingham's score for assessment of 10 years cardiovascular risk of individual patient before initiation and after completion of 6 months ADT. Serum lipid profile (fasting), systolic blood pressure, history of smoking, diabetes and antihypertensive medication were recorded. Proforma was designed to get clinical information. A p-value of <0.05 was considered significant. A paired-samples t-test was conducted to compare Framingham cardiovascular risk scores before initiation and after completion of 6 months ADT. Results: We enrolled 30 men with high/intermediate risk localized prostate cancer. Mean age was 63.47 +- 7.32 years. All patients received 6 months ADT with monthly 3.75mg leuprorelin acetate intramuscular injection. There was a significant difference in Framingham cardiovascular risk scores before (mean +- sd; 20.95 +- 7.98) and after (mean +- sd; 25.72 +- 6.15) 6 months ADT; t (29) =-4.54, p<0.01, two-tailed. Hence ADT resulted in a significant increase (mean +- sd; 25.7 +- 6.15) in 10 years cardiovascular morbidity risk t (29) =-4.54, p<0.01, two tailed. Subset analyses revealed significant increase in fasting serum total cholesterol, triglycerides and Low density lipoprotein (LDL) levels after 6 months ADT (p<0.01, <0.01 and <0.01 respectively) however high density lipoprotein (HDL) remained un-changed (p=0.043) in

Epigenetics in breast and prostate cancer.

Science.gov (United States)

Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V

2015-01-01

Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methylation profiles have been linked to hormone receptor status and tumor progression. Similarly in prostate cancer, epigenetic patterns have been associated with androgen receptor status and response to therapy. The regulation of key receptor pathways and activities which affect clinical therapy treatment options by epigenetics renders this field high priority for elucidating mechanisms and potential targets. A new set of methylation arrays are now available to screen epigenetic changes and provide the cutting-edge tools needed to perform such investigations. The role of nutritional interventions affecting epigenetic changes particularly holds promise. Ultimately, determining the causes and outcomes from epigenetic changes will inform translational applications for utilization as biomarkers for risk and prognosis as well as candidates for therapy.

Prostate-specific antigen and radiation therapy for clinically localized prostate cancer

International Nuclear Information System (INIS)

Zagars, Gunar K.; Pollack, Alan; Kavadi, Vivek S.; Eschenbach, Andrew C. von

1995-01-01

Purpose: This study was undertaken to: (a) define the prognostic significance of pretreatment serum prostate-specific antigen (PSA) levels in localized prostate cancer treated with radiation; (b) define the prognostic usefulness of postradiation PSA levels; (c) evaluate the outcome of radiation using PSA as an endpoint. Methods and Materials: Disease outcome in 707 patients with Stages T1 (205 men), T2 (256 men), T3 (239 men), and T4 (7 men), receiving definitive external radiation as sole therapy, was evaluated using univariate and multivariate techniques. Results: At a mean follow-up of 31 months, 157 patients (22%) developed relapse or a rising PSA. Multivariate analysis revealed pretreatment PSA level to be the most significant prognostic factor, with lesser though significant contributions due to Gleason grade (2-6 vs. 7-10) and transurethral resection in (T3(T4)) disease. The following four prognostic groupings were defined: group I, PSA ≤ 4 ng/ml, any grade; group II, 4 20, any grade. Five-year actuarial relapse rates in these groups were: I, 12%; II, 34%; III, 40%; and IV, 81%. Posttreatment nadir PSA was an independent determinant of outcome and only patients with nadir values < 1 ng/ml fared well (5-year relapse rate 20%). Using rising PSA as an endpoint the 461 patients with (T1(T2)) disease had an actuarial freedom from disease rate of 70% at 5 years, which appeared to plateau, suggesting that many were cured. No plateau was evident for (T3(T4)) disease. Conclusion: Pretreatment serum PSA is the single most important predictor of disease outcome after radiation for local prostate cancer. Tumor grade has a lesser though significant prognostic role. Postirradiation nadir PSA value during the first year is a sensitive indicator of response to treatment. Only nadir values < 1 ng/ml are associated with a favorable outlook. A significant fraction of men with (T1(T2)) disease may be cured with radiation. There was no evidence for a cured fraction among

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy

OpenAIRE

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-01-01

Abstract Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high?dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 2...

The new era of minimally invasive interventions for prostate cancer: robot-assisted laparoscopic radical prostatectomy and focal therapy

Directory of Open Access Journals (Sweden)

Schatloff O

2011-10-01

Full Text Available Oscar Schatloff1, Alyssa S Louis2, Uri Lindner21Global Robotics Institute, Florida Hospital Celebration Health, Celebration, FL, USA; 2Division of Urology, Department of Surgical Oncology, University Health Network, Toronto, ON, CanadaAbstract: Prostate cancer remains a common but highly treatable disease. Innovations in prostate cancer treatment have allowed a transition toward minimally invasive approaches in an attempt to avoid treatment-related morbidities. In the middle of the treatment spectrum between radical open surgeries and active surveillance lies robot-assisted laparoscopic radical prostatectomy (RALP and focal therapy (FT. This review sets out the most current information on RALP and FT (including laser ablation, cryotherapy, high-intensity focused ultrasound, photodynamic therapy, and irreversible electroporation.Keywords: PCa, RALP, FT, laser ablation, cryotherapy, high-intensity focused ultrasound, photodynamic therapy, irreversible electroporation

Identification, diagnostic assistance and planning methods that use multi-modality imaging for prostate cancer focal therapies

International Nuclear Information System (INIS)

Makni, Nasr

2010-01-01

Prostate cancer is one of the leading causes of death from cancer among men. In In the last decade, new diagnosis procedures and treatment options have been developed and made possible thanks to the recent progress in prostate imaging modalities. The newest challenges in this field are to detect the smallest tumors and to treat locally to minimise the treatment morbidity. In this thesis, we introduce a set of automatic image processing methods for the guidance and assistance of diagnosis and treatment, in laser-based prostate cancer focal therapies. In the first part of this work, segmentation and computer-aided detection algorithms have been developed for the enhancement of image-based diagnosis of prostate cancer. First, we propose a novel approach that combines Markov Random Fields framework with an Active Shape Model, in order to extract three dimensional outlines of the gland from Magnetic Resonance Imaging (MRI) data. Second, prostate's MRI volume is segmented into peripheral and central zones: we introduce a method that explores features of multispectral MRI, and is based on belief functions and the modelling of an a priori knowledge as an additional source of information. Finally, computer-aided detection of prostate's peripheral zone tumors is investigated by experimenting novel texture features based on fractal geometry-based. These parameters, extracted from morphological MRI, were tested using both supervised and unsupervised classification methods. The results of these different approaches were studied and compared. The second part of this work addresses the guidance of laser-based focal ablation of prostate tumors. A novel non rigid registration method is introduced for fusion of pre-operative MRI and planning data, and per-operative ultrasound imaging. We test and evaluate our algorithms using simulated data and physical phantoms, which enable comparison to ground truth. Patients' data, combined to expert interpretation, are also used in the

Longitudinal analysis of quality of life in patients receiving conformal radiation therapy for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Geinitz, Hans; Thamm, Reinhard; Scholz, Christian; Heinrich, Christine; Prause, Nina; Kerndl, Simone; Molls, Michael; Zimmermann, Frank B. [Dept. of Radiotherapy and Radiooncology, Technische Univ. Muenchen (Germany); Keller, Monika [Psychooncology Section, Dept. of Psychosomatic and General Clinical Medicine, Univ. Hospital, Heidelberg (Germany); Busch, Raymonde [Inst. of Medical Statistics and Epidemiology, Technische Univ. Muenchen (Germany)

2010-01-15

Purpose: To prospectively assess quality of life (QoL) in patients receiving conformal radiation therapy (CRT) for prostate cancer. Patients and Methods: 78 men with definitive CRT for prostate cancer were entered into the study. Patients were assessed before CRT, at 40 and 60 Gy, and 2, 12 and 24 months after the end of treatment. QoL was assessed using the EORTC Quality of Life Questionnaire C30 and the prostate module PR25. Changes in mean QoL scores with time of {>=} 10 points were considered clinically relevant. Results: Global QoL did not change statistically significant during CRT and was slightly above baseline levels during follow-up. CRT had a statistically significant negative short-term impact on role functioning, fatigue, and PR25 urinary symptoms. The scores recovered within 2 months to 1 year after CRT. Emotional functioning and social functioning scores slightly increased during and after CRT. Role functioning decreased by > 10 points at 60 Gy and urinary symptoms decreased by > 10 points at 40 and 60 Gy. All other differences were < 10 points. A high number of concomitant diseases and having no children were negative pretreatment predictors for long-term global QoL. Conclusion: Definitive CRT for prostate cancer does not compromise global QoL during therapy and up to 2 years after treatment. It has a limited negative effect on role functioning, urinary symptoms and, to a lesser extent, on fatigue with restitution within 2 months to 1 year after treatment. (orig.)

Longitudinal analysis of quality of life in patients receiving conformal radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Geinitz, Hans; Thamm, Reinhard; Scholz, Christian; Heinrich, Christine; Prause, Nina; Kerndl, Simone; Molls, Michael; Zimmermann, Frank B.; Keller, Monika; Busch, Raymonde

2010-01-01

Purpose: To prospectively assess quality of life (QoL) in patients receiving conformal radiation therapy (CRT) for prostate cancer. Patients and Methods: 78 men with definitive CRT for prostate cancer were entered into the study. Patients were assessed before CRT, at 40 and 60 Gy, and 2, 12 and 24 months after the end of treatment. QoL was assessed using the EORTC Quality of Life Questionnaire C30 and the prostate module PR25. Changes in mean QoL scores with time of ≥ 10 points were considered clinically relevant. Results: Global QoL did not change statistically significant during CRT and was slightly above baseline levels during follow-up. CRT had a statistically significant negative short-term impact on role functioning, fatigue, and PR25 urinary symptoms. The scores recovered within 2 months to 1 year after CRT. Emotional functioning and social functioning scores slightly increased during and after CRT. Role functioning decreased by > 10 points at 60 Gy and urinary symptoms decreased by > 10 points at 40 and 60 Gy. All other differences were < 10 points. A high number of concomitant diseases and having no children were negative pretreatment predictors for long-term global QoL. Conclusion: Definitive CRT for prostate cancer does not compromise global QoL during therapy and up to 2 years after treatment. It has a limited negative effect on role functioning, urinary symptoms and, to a lesser extent, on fatigue with restitution within 2 months to 1 year after treatment. (orig.)

Multiparametric MRI of the prostate. Method for early detection of prostate cancer?

International Nuclear Information System (INIS)

Schlemmer, Heinz-Peter

2010-01-01

Current approaches for the early detection of prostate cancer are controversially discussed because the disease is characterized by a high incidence rate with a relatively low morbidity rate, availability of only limited prognostic markers, and continued therapy-related morbidity. Conventional morphological MRI does not play a role in early detection since small tumor foci cannot be delineated. However, if there is clinical suspicion for prostate cancer, multiparametric MRI is currently the most accurate method for detecting and characterizing suspicious lesions in the prostate. The potential to identify the so-called 'index lesion', i.e., the tumor area that is most aggressive and determines treatment, is particularly important. This information can increase the accuracy of prostate biopsy and serve as a biomarker for follow-up during active surveillance. The method may considerably contribute to the urgently required separation of clinically significant from clinically insignificant prostate cancers. (orig.)

Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

Directory of Open Access Journals (Sweden)

Piotr Milecki

2010-10-01

Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

Prostate cancer and radiation therapy--the message conveyed by serum prostate-specific antigen

International Nuclear Information System (INIS)

Zagars, Gunar K.; Pollack, Alan; Eschenbach, Andrew C. von

1995-01-01

Purpose: Prostate-specific antigen (PSA) is a powerful pretreatment prognosticator and a sensitive post-treatment outcome measure for clinically localized prostate cancer treated with radiation therapy. Today, the pretreatment serum PSA level appears to supersede both grade and T-stage as a determinant of outcome. This study was undertaken to attempt a reconciliation between the old (pre-PSA) and the new (PSA) data-in particular to address the question of why stage and grade apparently play so little role in this PSA era. Methods and Materials: We analyzed the outcome of two cohorts of men with T1-T4, N0, or NX, M0 prostate cancer, one group (648 patients) treated and followed in the pre-PSA era (1966-1988), another group (707 patients) treated and followed in the PSA era (1987-1993)--who received definitive radiation as their only initial treatment. The patterns of relapse and prognostic factors for these groups were compared and contrasted using univariate and multivariate techniques. Results: At a median follow-up of 6.5 years, the relapse patterns in the pre-PSA series were: local in 109 (17%), nodal in 17 (3%), and distant metastatic in 186 (29%). Actuarial local and metastatic rates at 5 years were 13 and 26%, respectively. Local recurrence was only weakly predictable, Gleason grade being the only significant, albeit weak, covariate. Metastatic failure, however, was highly significantly and meaningfully correlated with Gleason grade and T-stage. Because metastasis was the most common adverse end point in this series, overall freedom from progression also correlated with grade and stage. At a median follow-up of 31 months, the patterns of failure in the PSA series were: local in 77 (11%), nodal in 3 (< 1%), and distant metastatic in 24 (3%). Actuarial local and metastatic rates at 5 years were 30 and 6%, respectively. Local recurrence was highly and meaningfully correlated with pretreatment PSA level, which was the only significant determinant of this end

Prostate cancer and radiation therapy--the message conveyed by serum prostate-specific antigen

Energy Technology Data Exchange (ETDEWEB)

Zagars, Gunar K; Pollack, Alan; Eschenbach, Andrew C. von

1995-08-30

Purpose: Prostate-specific antigen (PSA) is a powerful pretreatment prognosticator and a sensitive post-treatment outcome measure for clinically localized prostate cancer treated with radiation therapy. Today, the pretreatment serum PSA level appears to supersede both grade and T-stage as a determinant of outcome. This study was undertaken to attempt a reconciliation between the old (pre-PSA) and the new (PSA) data-in particular to address the question of why stage and grade apparently play so little role in this PSA era. Methods and Materials: We analyzed the outcome of two cohorts of men with T1-T4, N0, or NX, M0 prostate cancer, one group (648 patients) treated and followed in the pre-PSA era (1966-1988), another group (707 patients) treated and followed in the PSA era (1987-1993)--who received definitive radiation as their only initial treatment. The patterns of relapse and prognostic factors for these groups were compared and contrasted using univariate and multivariate techniques. Results: At a median follow-up of 6.5 years, the relapse patterns in the pre-PSA series were: local in 109 (17%), nodal in 17 (3%), and distant metastatic in 186 (29%). Actuarial local and metastatic rates at 5 years were 13 and 26%, respectively. Local recurrence was only weakly predictable, Gleason grade being the only significant, albeit weak, covariate. Metastatic failure, however, was highly significantly and meaningfully correlated with Gleason grade and T-stage. Because metastasis was the most common adverse end point in this series, overall freedom from progression also correlated with grade and stage. At a median follow-up of 31 months, the patterns of failure in the PSA series were: local in 77 (11%), nodal in 3 (< 1%), and distant metastatic in 24 (3%). Actuarial local and metastatic rates at 5 years were 30 and 6%, respectively. Local recurrence was highly and meaningfully correlated with pretreatment PSA level, which was the only significant determinant of this end

Intensity Modulated Radiation Therapy in Prostate Cancer

International Nuclear Information System (INIS)

Chacon, C.; Galli, M.; Meoli, P.; Mariani, L.; Novelli, L.; Gonzalez, G.

2008-01-01

Full text: Objective: To analyze the feasibility of high dose assessing acute and late toxicities both rectal and genitourinary in patients with clinically localized prostate cancer. Material and methods: Between April 2006 and April 2008 90 patients diagnosed with clinically localized prostate cancer were treated with MRT technique in the Department of Radiotherapy. The analysis included 80 patients, 10 of them in treatment. The total dose received was 80 Gy. One patient received 70.2 Gy (because of previous pelvic radiotherapy). Age average: 65 (r 43-85 years). Stage: T1c: 43 p (53.75%), T2: 35 p (43.75%), T3: 1 p (1.25%). Score of Gleason 10 ng/ml and [es

Neuroendorine differentiation in prostate cancer: A mechanism of radioresistance and treatment failure

Directory of Open Access Journals (Sweden)

Chang-Deng eHu

2015-04-01

Full Text Available Neuroendocrine differentiation (NED in prostate cancer is a well recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like cells. NE-like cells lack the expression of androgen receptor and prostate specific antigen, and are resistant to treatments. In addition, NE-like cells secrete peptide hormones and growth factors to support the growth of surrounding tumor cells in a paracrine manner. Accumulated evidence has suggested that NED is associated with disease progression and poor prognosis. The importance of NED in prostate cancer progression and therapeutic response is further supported by the fact that therapeutic agents, including androgen deprivation therapy, chemotherapeutic agents, and radiotherapy, also induce NED. We will review the work supporting the overall hypothesis that therapy-induced NED is a mechanism of resistance to treatments, as well as discuss the relationship between therapy-induced NED and therapy-induced senescence, epithelial-to-mesenchymal transition, and cancer stem cells. Furthermore, we will use radiation-induced NED as a model to explore several NED-based targeting strategies for development of novel therapeutics. Finally, we propose future studies that will specifically address therapy-induced NED in the hope that a better treatment regimen for prostate cancer can be developed.

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

NARCIS (Netherlands)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; van der Heide, Uulke A.; van Herk, Marcel; Heemsbergen, Wilma D.

2015-01-01

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions

Current state of prostate cancer treatment in Jamaica.

Science.gov (United States)

Morrison, Belinda F; Aiken, William D; Mayhew, Richard

2014-01-01

Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

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Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Viset, Trond [Department of Pathology, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Wibe, Arne [Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim (Norway); Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); Kaasa, Stein [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); European Palliative Care Research Center, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim (Norway); Widmark, Anders [Department of Radiation Sciences, Cancercentrum, Umeå (Sweden); Lund, Jo-Åsmund [Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim (Norway); European Palliative Care Research Center, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim (Norway)

2016-07-15

Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analytic (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.

Current Stem Cell Biomarkers and Their Functional Mechanisms in Prostate Cancer

Directory of Open Access Journals (Sweden)

Kaile Zhang

2016-07-01

Full Text Available Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients.

The Impact of Brachytherapy on Prostate Cancer–Specific Mortality for Definitive Radiation Therapy of High-Grade Prostate Cancer: A Population-Based Analysis

International Nuclear Information System (INIS)

Shen Xinglei; Keith, Scott W.; Mishra, Mark V.; Dicker, Adam P.; Showalter, Timothy N.

2012-01-01

Purpose: This population-based analysis compared prostate cancer–specific mortality (PCSM) in a cohort of patients with high-risk prostate cancer after nonsurgical treatment with external beam radiation therapy (EBRT), brachytherapy (BT), or combination (BT + EBRT). Methods and Materials: We identified from the Surveillance, Epidemiology and End Results database patients diagnosed from 1988 through 2002 with T1–T3N0M0 prostate adenocarcinoma of poorly differentiated grade and treated with BT, EBRT, or BT + EBRT. During this time frame, the database defined high grade as prostate cancers with Gleason score 8–10, or Gleason grade 4–5 if the score was not recorded. This corresponds to a cohort primarily with high-risk prostate cancer, although some cases where only Gleason grade was recorded may have included intermediate-risk cancer. We used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on PCSM. Results: There were 12,745 patients treated with EBRT (73.5%), BT (7.1%), or BT + EBRT (19.4%) included in the analysis. The median follow-up time for all patients was 6.4 years. The use of BT or BT + EBRT increased from 5.1% in 1988–1992 to 31.4% in 1998–2002. Significant predictors of use of BT or BT + EBRT were younger age, later year of diagnosis, urban residence, and earlier T-stage. On multivariate analysis, treatment with either BT (hazard ratio, 0.66; 95% confidence interval, 0.49–0.86) or BT + EBRT (hazard ratio, 0.77; 95% confidence ratio, 0.66–0.90) was associated with significant reduction in PCSM compared with EBRT alone. Conclusion: In patients with high-grade prostate cancer, treatment with brachytherapy is associated with reduced PCSM compared with EBRT alone. Our results suggest that brachytherapy should be investigated as a component of definitive treatment strategies for patients with high-risk prostate cancer.

Prostatic biopsy after irradiation therapy for prostatic cancer

International Nuclear Information System (INIS)

Scardino, P.T.; Wheeler, T.M.

1985-01-01

To determine the prognostic significance of a routine needle biopsy of the prostate performed six to thirty-six months after the completion of definitive radiotherapy, biopsy results were analyzed in 146 patients who had no evidence of disease at the time of biopsy and who received no other therapy before proved recurrence of the tumor. Patients were followed up a mean of 3.9 years after radioactive gold seed implantation and external beam irradiation. The total dose was 8,000 rad. Among 146 patients, 56 (38%) had one or more positive biopsy results within this time interval. The positive biopsy rate correlated with the clinical stage ranging from 17 per cent in Stage B1N to 59 per cent in Stage C1. The risk of developing local recurrence or distant metastases at any given time after irradiation therapy was markedly greater in those patients with a positive biopsy result (p less than 0.0005). Prostatic biopsy is an accurate means of measuring the success of radiotherapy. A positive postirradiation biopsy result carries grave prognostic implications for the patient and indicates that the treatment has failed

Stages of Prostate Cancer

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... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer Go to Health Professional Version Key Points Prostate ...

Prostate Cancer FAQs

Science.gov (United States)

... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer FAQs Top 10 Things You Should Know About ... prostate cancer detected? What are the symptoms of prostate cancer? If the cancer is caught at its earliest ...

Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature.

Science.gov (United States)

Srivatsa, N; Nagaraja, H; Shweta, S; Raghunath, S K

2017-06-01

Twenty-five to thirty percent of patients with prostate cancer present with locally advanced disease. While risk stratification remains the same with high incidence of upstaging of disease on imaging and histopathological evaluation; there have been progressive refinements in surgical therapy. With availability of reasonably robust data, radical prostatectomy in men with locally advanced prostate cancers seems to effect improvement in both cancer specific and overall survival rates in comparison to the current standard of care of radiation with androgen deprivation therapy. Studies using radical prostatectomy as a part of multimodality approach have also shown promising results. There is an imminent need for well-designed prospective studies of benefits of radical prostatectomy over radiation and androgen deprivation as well as benefits of multimodality therapy over monotherapy. Surgery for patients with locally advanced prostate cancer is technically challenging. Surgical outcomes are comparable to those of organ-confined disease when performed in high-volume centers. Neoadjuvant therapies prior to radical prostatectomy might improve surgical outcomes, but whether they will translate into a better cancer specific and overall survival are yet to be ascertained.

A software tool for advanced MRgFUS prostate therapy planning and follow up

Science.gov (United States)

van Straaten, Dörte; Hoogenboom, Martijn; van Amerongen, Martinus J.; Weiler, Florian; Issawi, Jumana Al; Günther, Matthias; Fütterer, Jurgen; Jenne, Jürgen W.

2017-03-01

US guided HIFU/FUS ablation for the therapy of prostate cancer is a clinical established method, while MR guided HIFU/FUS applications for prostate recently started clinical evaluation. Even if MRI examination is an excellent diagnostic tool for prostate cancer, it is a time consuming procedure and not practicable within an MRgFUS therapy session. The aim of our ongoing work is to develop software to support therapy planning and post-therapy follow-up for MRgFUS on localized prostate cancer, based on multi-parametric MR protocols. The clinical workflow of diagnosis, therapy and follow-up of MR guided FUS on prostate cancer was deeply analyzed. Based on this, the image processing workflow was designed and all necessary components, e.g. GUI, viewer, registration tools etc. were defined and implemented. The software bases on MeVisLab with several implemented C++ modules for the image processing tasks. The developed software, called LTC (Local Therapy Control) will register and visualize automatically all images (T1w, T2w, DWI etc.) and ADC or perfusion maps gained from the diagnostic MRI session. This maximum of diagnostic information helps to segment all necessary ROIs, e.g. the tumor, for therapy planning. Final therapy planning will be performed based on these segmentation data in the following MRgFUS therapy session. In addition, the developed software should help to evaluate the therapy success, by synchronization and display of pre-therapeutic, therapy and follow-up image data including the therapy plan and thermal dose information. In this ongoing project, the first stand-alone prototype was completed and will be clinically evaluated.

Variation of clinical target volume definition in three-dimensional conformal radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Valicenti, Richard K.; Sweet, John W.; Hauck, Walter W.; Hudes, Richard S.; Lee, Tony; Dicker, Adam P.; Waterman, Frank M.; Anne, Pramila R.; Corn, Benjamin W.; Galvin, James M.

1999-01-01

Purpose: Currently, three-dimensional conformal radiation therapy (3D-CRT) planning relies on the interpretation of computed tomography (CT) axial images for defining the clinical target volume (CTV). This study investigates the variation among multiple observers to define the CTV used in 3D-CRT for prostate cancer. Methods and Materials: Seven observers independently delineated the CTVs (prostate ± seminal vesicles [SV]) from the CT simulation data of 10 prostate cancer patients undergoing 3D-CRT. Six patients underwent CT simulation without the use of contrast material and serve as a control group. The other 4 had urethral and bladder opacification with contrast medium. To determine interobserver variation, we evaluated the derived volume, the maximum dimensions, and the isocenter for each examination of CTV. We assessed the reliability in the CTVs among the observers by correlating the variation for each class of measurements. This was estimated by intraclass correlation coefficient (ICC), with 1.00 defining absolute correlation. Results: For the prostate volumes, the ICC was 0.80 (95% confidence interval [CI]: 0.56-0.96). This changed to 0.92 (95% CI: 0.75-0.99) with the use of contrast material. Similarly, the maximal prostatic dimensions were reliable and improved. There was poor agreement in defining the SV. For this structure, the ICC never exceeded 0.28. The reliability of the isocenter was excellent, with the ICC exceeding 0.83 and 0.90 for the prostate ± SV, respectively. Conclusions: In 3D-CRT for prostate cancer, there was excellent agreement among multiple observers to define the prostate target volume but poor agreement to define the SV. The use of urethral and bladder contrast improved the reliability of localizing the prostate. For all CTVs, the isocenter was very reliable and should be used to compare the variation in 3D dosimetry among multiple observers

Lactate - A new frontier in the immunology and therapy of prostate cancer.

Science.gov (United States)

Nenu, Iuliana; Gafencu, Grigore-Aristide; Popescu, Tiberiu; Kacso, Gabriel

2017-01-01

Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators. In addition, lactate inhibits the differentiation of monocytes and dendritic cells and also induces the inactivation of the cytotoxic T-lymphocytes. Through an analysis of recent studies, we conclude that lactate is a vital component of several ways of modulating the immune response at the stromal prostatic adenocarcinoma including TAM activation and cytotoxic T lymphocytes immunosuppression. Our review focuses on the impact of lactate on prostatic adenocarcinoma progression in terms of its immunology, and how this influences the therapy of this condition and the clinical outcome.

New Insights into the Androgen-Targeted Therapies and Epigenetic Therapies in Prostate Cancer

Directory of Open Access Journals (Sweden)

Abhijit M. Godbole

2011-01-01

Full Text Available Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR, a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC. Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes, posttranslational modifications of AR such as sumoylation. Herein, we provide an overview of the structure of human AR and its key structural domains that can be used as targets to develop novel antiandrogens. We also summarize recent findings about the antiandrogens and the epigenetic factors that modulate the action of AR.

Selective Androgen Receptor Down-Regulators (SARDs): A New Prostate Cancer Therapy

National Research Council Canada - National Science Library

Bhattacharyya, Rumi S

2007-01-01

The androgen receptor (AR) plays a key role in the development and progression of prostate cancer Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory...

Imaging Cellular Proliferation in Prostate Cancer with Positron Emission Tomography

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Hossein Jadvar

2015-07-01

Full Text Available Prostate cancer remains a major public health problem worldwide. Imaging plays an important role in the assessment of disease at all its clinical phases, including staging, restaging after definitive therapy, evaluation of therapy response, and prognostication. Positron emission tomography with a number of biologically targeted radiotracers has been demonstrated to have potential diagnostic and prognostic utility in the various clinical phases of this prevalent disease. Given the remarkable biological heterogeneity of prostate cancer, one major unmet clinical need that remains is the non-invasive imaging-based characterization of prostate tumors. Accurate tumor characterization allows for image-targeted biopsy and focal therapy as well as facilitates objective assessment of therapy effect. PET in conjunction with radiotracers that track the thymidine salvage pathway of DNA synthesis may be helpful to fulfill this necessity. We review briefly the preclinical and pilot clinical experience with the two major cellular proliferation radiotracers, [18F]-3’-deoxy-3’-fluorothymidine and [18F]-2’-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil in prostate cancer.

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

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Lewis, Stephen L.; Patel, Pretesh; Song, Haijun [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Freedland, Stephen J. [Surgery Section, Durham Veterans Administration, and Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California (United States); Bynum, Sigrun; Oh, Daniel; Palta, Manisha; Yoo, David; Oleson, James [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Salama, Joseph K., E-mail: joseph.salama@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

2016-03-01

Purpose: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. Methods and Materials: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Results: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a

Microscopic Gold Particle-Based Fiducial Markers for Proton Therapy of Prostate Cancer

International Nuclear Information System (INIS)

Lim, Young Kyung; Kwak, Jungwon; Kim, Dong Wook; Shin, Dongho; Yoon, Myonggeun; Park, Soah; Kim, Jin Sung; Ahn, Sung Hwan; Shin, Jungwook; Lee, Se Byeong; Park, Sung Yong; Pyo, Hong Ryeol; Kim, Dae Yong M.D.; Cho, Kwan Ho

2009-01-01

Purpose: We examined the feasibility of using fiducial markers composed of microscopic gold particles and human-compatible polymers as a means to overcome current problems with conventional macroscopic gold fiducial markers, such as dose reduction and artifact generation, in proton therapy for prostate cancer. Methods and Materials: We examined two types of gold particle fiducial marker interactions: that with diagnostic X-rays and with a therapeutic proton beam. That is, we qualitatively and quantitatively compared the radiographic visibility of conventional gold and gold particle fiducial markers and the CT artifacts and dose reduction associated with their use. Results: The gold particle fiducials could be easily distinguished from high-density structures, such as the pelvic bone, in diagnostic X-rays but were nearly transparent to a proton beam. The proton dose distribution was distorted <5% by the gold particle fiducials with a 4.9% normalized gold density; this was the case even in the worst configuration (i.e., parallel alignment with a single-direction proton beam). In addition, CT artifacts were dramatically reduced for the gold particle mixture. Conclusion: Mixtures of microscopic gold particles and human-compatible polymers have excellent potential as fiducial markers for proton therapy for prostate cancer. These include good radiographic visibility, low distortion of the depth-dose distribution, and few CT artifacts.

Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

International Nuclear Information System (INIS)

Pugh, Thomas J.; Munsell, Mark F.; Choi, Seungtaek; Nguyen, Quyhn Nhu; Mathai, Benson; Zhu, X. Ron; Sahoo, Narayan; Gillin, Michael; Johnson, Jennifer L.; Amos, Richard A.; Dong, Lei; Mahmood, Usama; Kuban, Deborah A.; Frank, Steven J.; Hoffman, Karen E.; McGuire, Sean E.; Lee, Andrew K.

2013-01-01

Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a

Prostate carcinoma: results of radiation therapy in the French Cancer Centres

International Nuclear Information System (INIS)

Allain, Y.M.; Bolla, M.; Douchez, J.; Gary-Bobo, J.; Geslin, J.; Huart, J.; Mazeron, J.J.; Mathieu, G.

1985-01-01

From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90% respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated [fr

PROSTVAC® targeted immunotherapy candidate for prostate cancer.

Science.gov (United States)

Shore, Neal D

2014-01-01

Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

International Nuclear Information System (INIS)

Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae

2016-01-01

This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV max and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV max were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV max was 4.7. In 16 patients who underwent follow-up PET/CT, SUV max was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment

Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey-Holden Prostate Cancer Academy Meeting.

Science.gov (United States)

Miyahira, Andrea K; Cheng, Heather H; Abida, Wassim; Ellis, Leigh; Harshman, Lauren C; Spratt, Daniel E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2017-11-01

The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer. The 2017 CHPCA Meeting was the 5th meeting in this annual series and was attended by 71 investigators focused on prostate cancer and a variety of other fields including breast and ovarian cancer. The discussions at the meeting were concentrated on topics areas including: mechanisms and therapeutic approaches for molecular subclasses of castrate resistant prostate cancer (CRPC), the epigenetic landscape of prostate cancer, the role of DNA repair gene mutations, advancing the use of germline genetics in clinical practice, radionuclides for imaging and therapy, advances in molecular imaging, and therapeutic strategies for successful use of immunotherapy in advanced prostate cancer. This article reviews the presentations and discussions from the 2017 CHPCA Meeting in order to disseminate this knowledge and accelerate new biological understandings and advances in the treatment of patients with metastatic prostate cancer. © 2017 Wiley Periodicals, Inc.

Dysuria Following Stereotactic Body Radiation Therapy for Prostate Cancer

Directory of Open Access Journals (Sweden)

Einsley-Marie eJanowski

2015-07-01

Full Text Available Background: Dysuria following prostate radiation therapy is a common toxicity that adversely affects patients’ quality of life and may be difficult to manage. Methods: 204 patients treated with stereotactic body radiation therapy (SBRT from 2007 to 2010 for localized prostate carcinoma with a minimum follow up of three years were included in this retrospective review of prospectively collected data. All patients were treated to 35-36.25Gy in 5 fractions delivered with robotic SBRT with real time fiducial tracking. Dysuria and other lower urinary tract symptoms were assessed via Question 4b (Pain or burning on urination of the Expanded Prostate Index Composite (EPIC-26 and the American Urological Association (AUA Symptom Score at baseline and at routine follow up. Results: 204 patients (82 low-, 105 intermediate-, and 17 high risk according to the D’Amico classification at a median age of 69 years (range 48-91 received SBRT for their localized prostate cancer with a median follow up of 47 months. Bother associated with dysuria significantly increased from a baseline of 12% to a maximum of 43% at one month (p<0.0001. There were two distinct peaks of moderate to severe dysuria bother at 1 month and at 6-12 months, with 9% of patients experiencing a late transient dysuria flare. While a low level of dysuria was seen through the first two years of follow-up, it returned to below baseline by two years (p=0.91. The median baseline AUA score of 7.5 significantly increased to 11 at 1 month (p<0.0001 and returned to 7 at 3 months (p= 0.54. Patients with dysuria had a statistically higher AUA score at baseline and at all follow-ups up to 30 months. Dysuria significantly correlated with dose and AUA score on multivariate analysis. Frequency and strain significantly correlated with dysuria on stepwise multivariate analysis.Conclusions: The rate and severity of dysuria following SBRT is comparable to patients treated with other radiation modalities.

Image-guided conformation arc therapy for prostate cancer: Early side effects

International Nuclear Information System (INIS)

Soete, Guy; Verellen, Dirk; Michielsen, Dirk; Rappe, Bernard; Keuppen, Frans; Storme, Guy

2006-01-01

Purpose: To evaluate early side effects in prostate cancer patients treated with image-guided conformation arc therapy (IGCAT) using a minimultileaf collimator and daily X-ray-assisted patient positioning. Methods and Materials: Between May 2000 and November 2004, 238 cT1-T3N0M0 tumors were treated with doses of 70 or 78 Gy. Seventy patients also received neoadjuvant or concurrent hormonal treatment. Median follow-up is 18 months (range, 4-55 months). Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity scoring system was used to evaluate early side effects. Results: Grade 1, 2, and >2 acute side effects occurred in 19, 6, and 0% (gastrointestinal) and 37, 16, and 0% (genitourinary) of the patients. No relation between radiation dose and early side effects was observed. Conclusion: Patients treated with image-guided conformation arc therapy experience a low rate of Grade 2 (i.e., requiring medication) early side effects. The definitive evaluation of late side effects and biochemical control requires further follow-up

Prostate cancer in renal transplant recipients

Directory of Open Access Journals (Sweden)

Benjamin A. Sherer

Full Text Available ABSTRACT As patients with end-stage renal disease are receiving renal allografts at older ages, the number of male renal transplant recipients (RTRs being diagnosed with prostate cancer (CaP is increasing. Historically, the literature regarding the management of CaP in RTR's is limited to case reports and small case series. To date, there are no standardized guidelines for screening or management of CaP in these complex patients. To better understand the unique characteristics of CaP in the renal transplant population, we performed a literature review of PubMed, without date limitations, using a combination of search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen kinetics, immuno-suppression, prostatectomy, and radiation therapy. Of special note, teams facilitating the care of these complex patients must carefully and meticulously consider the altered anatomy for surgical and radiotherapeutic planning. Active surveillance, though gaining popularity in the general low risk prostate cancer population, needs further study in this group, as does the management of advance disease. This review provides a comprehensive and contemporary understanding of the incidence, screening measures, risk stratification, and treatment options for CaP in RTRs.

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

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Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-12-01

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

Prostate Cancer

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... breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Obesity. Obese men diagnosed with prostate cancer may be more likely ...

Prostate Cancer Symptoms

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... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer Symptoms and Signs Prostate Cancer Basics Risk Factors ... earlier. So what are the warning signs of prostate cancer? Unfortunately, there usually aren’t any early warning ...

Prostate cancer - treatment

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... page: //medlineplus.gov/ency/patientinstructions/000403.htm Prostate cancer - treatment To use the sharing features on this page, ... drugs is recommended. References National Cancer Institute. Prostate cancer treatment (PDQ): Stages of prostate cancer. Updated July 31, ...

Perceived barriers and facilitators to physical activity in men with prostate cancer: possible influence of androgen deprivation therapy.

Science.gov (United States)

Keogh, J W L; Patel, A; MacLeod, R D; Masters, J

2014-03-01

While physical activity is beneficial for men with prostate cancer, too few perform sufficient activity for such benefit. This study examined perceptions of men with prostate cancer of their barriers and facilitators to physical activity, and how androgen deprivation therapy (ADT) may influence these perceptions. Two focus groups were conducted, involving six ADT and eight non-ADT patients respectively. Data were transcribed verbatim and themes developed using a general inductive thematic approach. Facilitators to physical activity common to both groups of cancer survivors included clinician and spousal involvement, with pre-existing co-morbidities and increased age cited as barriers by both groups. The ADT subgroup cited personal involvement as a facilitator to physical activity, with fatigue, reduced motivation and a relative lack of specific advice from their clinician as additional barriers. The non-ADT subgroup had no additional facilitators to physical activity but cited time constraints as a barrier. These results highlight the important role that cancer clinicians and spouses play in promoting physical activity for men with prostate cancer and how ADT may influence their other facilitators and barriers. As physical activity is beneficial for prostate cancer survivors, especially those on ADT, cancer clinicians should regularly discuss physical activity with their patients. © 2013 John Wiley & Sons Ltd.

Pomegranate and Its Components as Alternative Treatment for Prostate Cancer

Science.gov (United States)

Wang, Lei; Martins-Green, Manuela

2014-01-01

Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. Recent research has shown that pomegranate juice (PJ) and/or pomegranate extracts (PE) significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA) doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis. PMID:25158234

Care of the cancer survivor: metabolic syndrome following hormone-modifying therapy

OpenAIRE

Redig, Amanda J.; Munshi, Hidayatullah G.

2010-01-01

Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies may increase patients’ risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones, thus treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardi...

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

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Strom, Tobin J.; Hutchinson, Sean Z.; Shrinath, Kushagra; Cruz, Alex A.; Figura, Nicholas B.; Nethers, Kevin; Biagioli, Matthew C.; Fernandez, Daniel C.; Heysek, Randy V.; Wilder, Richard B., E-mail: richard.wilder@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

2014-07-15

Purpose: To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods: From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results: Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions: There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. (author)

Novel Therapeutic Approaches Toward Treating Prostate Cancer

Science.gov (United States)

2013-05-01

Kinases, Prostate Cancer, AKT inhibition, Mouse, Prostate Stem Cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...Bearss 0, Wierda WG, Gandhi V (2009) Pim kinase inhibitor, 5GI-1776, induces apoptosis in CLL lymphocytes. Blood 114:4150--4157. 27. Grey R, et aL...PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem eel! transplantation and rituximab: a Cancer and Leukemia

A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer. Results at median follow-up of 102 months

International Nuclear Information System (INIS)

Akakura, Koichiro; Suzuki, Hiroyoshi; Ichikawa, Tomohiko

2006-01-01

The background of this study was to investigate the optimal treatment of locally advanced prostate cancer, a prospective randomized trial was conducted to compare radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy. One hundred patients with T2b-3N0M0 prostate cancer were enrolled and 95 were evaluated. Of 95 cases, 46 underwent radical prostatectomy with pelvic lymph node dissection and 49 were treated with external beam radiation by linear accelerator with 40-50 Gy to the whole pelvis and 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiotherapy and continued thereafter. The long-term outcome and morbidity were examined. Median follow-up period was 102 months. At 10 years overall survival rates in the surgery group were better than the radiation group (76.2% versus 71.1% for biochemical progression-free rates; P=0.25, 83.5% versus 66.1% for clinical progression-free rates; P=0.14, 85.7% versus 77.1% for cause-specific survival rates; P=0.06, and 67.9% versus 60.9% for overall survival rates; P=0.30), although none of them reached statistical significance. Erectile dysfunction was recognized in almost all patients as a result of continuous endocrine therapy. Incontinence requiring more than one pad per day was observed more frequently in the surgery group than the radiation group (P<0.01). For the treatment of patients with locally advanced prostate cancer, when combined with endocrine therapy, either radical prostatectomy or external beam radiotherapy demonstrated favorable long-term outcomes. The radiation dose of 60-70 Gy might not be enough for the local treatment of locally advanced prostate cancer. (author)

Five-year follow-up of health-related quality of life after intensity-modulated radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Namiki, Shunichi; Ishidoya, Shigeto; Ito, Akihiro; Narazaki, Kakutaro; Yamada, Shogo; Takai, Yoshihiro; Arai, Yoichi; Tochigi, Tatsuo; Numata, Isao

2009-01-01

We evaluated health-related quality of life (HRQOL) in patients with localized prostate cancer who underwent intensity-modulated radiation therapy (IMRT) or three-field conformal radiotherapy (3DCRT). A total of 97 patients underwent 3DCRT and 36 underwent IMRT for localized prostate cancer between 2002 and 2004. We measured the general and disease-specific HRQOL with the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles Prostate Cancer Index, respectively. There were no significant differences in the pre-operative characteristics of the two groups. The patients in the 3DCRT group were more likely to receive hormonal therapy compared with the IMRT group before and after radiation therapy (P<0.001 and P=0.011, respectively). With regard to general HRQOL domains, both the 3DCRT and IMRT group scores showed no significant difference between baseline and any of the observation periods. At 60 months after treatment, the 3DCRT group had significantly worse bowel function and bother scores than baseline (both P<0.001). On the other hand, there were no significant differences between the baseline and any of the post-treatment time periods in the IMRT group. In the 3DCRT group, sexual function remained substantially lower than the baseline level (P=0.023). The IMRT group tended to show a decrease in sexual function, which was not statistically significant (P=0.11). IMRT can provide the possibility to deliver a high irradiation dose to the prostate with satisfactory functional outcomes for long-term periods. (author)

Oxidative Stress and DNA Methylation in Prostate Cancer

Directory of Open Access Journals (Sweden)

Krishna Vanaja Donkena

2010-01-01

Full Text Available The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin-associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy.

MAIN MOLECULAR TARGETS FOR PROSTATE CANCER THERAPY

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G. S. Krasnov

2014-01-01

Full Text Available Androgenic pathway plays a pivotal role in the development of benign and malignant prostate tumors. Most of the prostate neoplasms are hormone-dependent at the time of diagnosis. Therapeutic interventions aimed at reducing the level of testosterone in the blood allow to stop progression of the disease. But over time, the tumor almost inevitably starts to progress, moving in the castration-resistant state (CRPC, representing a serious problem of oncourology. In recent years, the possibility of CRRPC therapy increased significantly – there was developed a number of new drugs that effectively inhibit the development of castration-resistant tumors and significantly push back the start of chemotherapy. This review describes the major drug targets and mechanisms of action of abiraterone, enzalutamide, galeterone, VT-464 and other approved and promising CRPC therapies.

Development of cell-penetrating bispecific antibodies targeting the N-terminal domain of androgen receptor for prostate cancer therapy.

Science.gov (United States)

Goicochea, Nancy L; Garnovskaya, Maria; Blanton, Mary G; Chan, Grace; Weisbart, Richard; Lilly, Michael B

2017-12-01

Castration-resistant prostate cancer cells exhibit continued androgen receptor signaling in spite of low levels of ligand. Current therapies to block androgen receptor signaling act by inhibiting ligand production or binding. We developed bispecific antibodies capable of penetrating cells and binding androgen receptor outside of the ligand-binding domain. Half of the bispecific antibody molecule consists of a single-chain variable fragment of 3E10, an anti-DNA antibody that enters cells. The other half is a single-chain variable fragment version of AR441, an anti-AR antibody. The resulting 3E10-AR441 bispecific antibody enters human LNCaP prostate cells and accumulates in the nucleus. The antibody binds to wild-type, mutant and splice variant androgen receptor. Binding affinity of 3E10-AR441 to androgen receptor (284 nM) was lower than that of the parental AR441 mAb (4.6 nM), but could be improved (45 nM) through alternative placement of the affinity tags, and ordering of the VH and VK domains. The 3E10-AR441 bispecific antibody blocked genomic signaling by wild-type or splice variant androgen receptor in LNCaP cells. It also blocked non-genomic signaling by the wild-type receptor. Furthermore, bispecific antibody inhibited the growth of C4-2 prostate cancer cells under androgen-stimulated conditions. The 3E10-AR441 biAb can enter prostate cancer cells and inhibits androgen receptor function in a ligand-independent manner. It may be an attractive prototype agent for prostate cancer therapy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

International Nuclear Information System (INIS)

Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

2006-01-01

Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

The MCT4 Gene: A Novel, Potential Target for Therapy of Advanced Prostate Cancer.

Science.gov (United States)

Choi, Stephen Yiu Chuen; Xue, Hui; Wu, Rebecca; Fazli, Ladan; Lin, Dong; Collins, Colin C; Gleave, Martin E; Gout, Peter W; Wang, Yuzhuo

2016-06-01

The management of castration-resistant prostate cancer (CRPC) is a major challenge in the clinic. Androgen receptor signaling-directed strategies are not curative in CRPC therapy, and new strategies targeting alternative, key cancer properties are needed. Using reprogrammed glucose metabolism (aerobic glycolysis), cancer cells typically secrete excessive amounts of lactic acid into their microenvironment, promoting cancer development, survival, and progression. Cellular lactic acid secretion is thought to be predominantly mediated by MCT4, a plasma membrane transporter protein. As such, the MCT4 gene provides a unique, potential therapeutic target for cancer. A tissue microarray of various Gleason grade human prostate cancers was stained for MCT4 protein. Specific, MCT4-targeting antisense oligonucleotides (MCT4 ASO) were designed and candidate MCT4 ASOs checked for effects on (i) MCT4 expression, lactic acid secretion/content, glucose consumption, glycolytic gene expression, and proliferation of human CRPC cells and (ii) growth of PC-3 tumors in nude mice. Elevated MCT4 expression was associated with human CRPC and an earlier time to relapse. The treatment of PC-3, DU145, and C4-2 CRPC cultures with candidate MCT4 ASOs led to marked inhibition of MCT4 expression, lactic acid secretion, to increased intracellular lactic acid levels, and markedly reduced aerobic glycolysis and cell proliferation. Treatment of PC-3 tumor-bearing nude mice with the MCT4 ASOs markedly inhibited tumor growth without inducing major host toxicity. MCT4-targeting ASOs that inhibit lactic acid secretion may be useful for therapy of CRPC and other cancers, as they can interfere with reprogrammed energy metabolism of cancers, an emerging hallmark of cancer. Clin Cancer Res; 22(11); 2721-33. ©2016 AACR. ©2016 American Association for Cancer Research.

Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

DEFF Research Database (Denmark)

Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick

2014-01-01

change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse......OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics....... PATIENTS AND METHODS: The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3...

General Information about Prostate Cancer

Science.gov (United States)

... of bisphosphonate drugs to prevent or slow the growth of bone metastases is being studied in clinical trials. There are treatments for bone pain caused by bone metastases or hormone therapy. Prostate cancer that has spread to the ...

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

Science.gov (United States)

Hu, Jieping; Wang, Gongxian; Sun, Ting

2017-05-01

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Clinical adenoviral gene therapy for prostate cancer

Czech Academy of Sciences Publication Activity Database

Schenk, E.; Essand, M.; Bangma, Ch. H.; Barber, Ch.; Behr, J.-P.; Briggs, S.; Carlisle, R.; Cheng, W.-S.; Danielsson, A.; Dautzenberg, I. J. C.; Dzojic, H.; Erbacher, P.; Fisher, K.; Frazier, A.; Georgopoulos, L. J.; Hoeben, R.; Kochanek, S.; Koppers-Lalic, D.; Kraaij, R.; Kreppel, F.; Lindholm, L.; Magnusson, M.; Maitland, N.; Neuberg, P.; Nilsson, B.; Ogris, M.; Remy, J.-S.; Scaife, M.; Schooten, E.; Seymour, L.; Totterman, T.; Uil, T. G.; Ulbrich, Karel; Veldhoven-Zweistra, J. L. M.; de Vrij, J.; van Weerden, W.; Wagner, E.; Willemsen, R.

2010-01-01

Roč. 21, č. 7 (2010), s. 807-813 ISSN 1043-0342 EU Projects: European Commission(XE) 512087 - GIANT Keywords : adenovirus * gene delivery * prostate cancer Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.829, year: 2010

Cognitive Impairment in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Sun, Maxine; Cole, Alexander P; Hanna, Nawar; Mucci, Lorelei A; Berry, Donna L; Basaria, Shehzad; Ahern, David K; Kibel, Adam S; Choueiri, Toni K; Trinh, Quoc-Dien

2018-06-01

Use of androgen deprivation therapy may increase the risk of cognitive impairment in men with prostate cancer. We performed a systematic review of the risk of overall cognitive impairment as an outcome in men receiving androgen deprivation therapy for prostate cancer. Studies were identified through PubMed®, MEDLINE®, PsycINFO®, Cochrane Library and Web of Knowledge/Science™. Articles were included if they 1) were published in English, 2) had subjects treated for prostate cancer with androgen deprivation therapy, 3) incorporated longitudinal comparisons and 4) used control groups. In addition, prospective studies were required to assess an established cognitive related end point using International Cognition and Cancer Task Force criteria defining impaired cognitive performance as scoring 1.5 or more standard deviations below published norms on 2 or more tests, or scoring 2.0 or more standard deviations below published norms on at least 1 test. The effect of androgen deprivation therapy on cognitive impairment was pooled using a random effects model. Of 221 abstracts 26 were selected for full text review, and 2 prospective and 4 retrospective studies were analyzed. Androgen deprivation therapy was not associated with overall cognitive impairment when the prospective cohort studies were pooled (OR 1.57, 95% CI 0.50 to 4.92, p = 0.44) with significant heterogeneity between estimates (I 2 = 83%). In retrospective data the relative risk of any cognitive impairment, including senile dementia and Alzheimer disease, was increased in men receiving androgen deprivation therapy, although the difference was not statistically significant (HR 1.28, 95% CI 0.93 to 1.76, p = 0.13) with moderate heterogeneity between estimates (I 2 = 67%). Analyses between overall cognitive impairment and use of androgen deprivation therapy defined according to International Cognition and Cancer Task Force criteria in a pooled analysis were inconclusive. In retrospective cohort studies the

Prostate-specific antigen and radiation therapy for clinically localized prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Zagars, Gunar K; Pollack, Alan; Kavadi, Vivek S; Eschenbach, Andrew C. von

1995-05-15

Purpose: This study was undertaken to: (a) define the prognostic significance of pretreatment serum prostate-specific antigen (PSA) levels in localized prostate cancer treated with radiation; (b) define the prognostic usefulness of postradiation PSA levels; (c) evaluate the outcome of radiation using PSA as an endpoint. Methods and Materials: Disease outcome in 707 patients with Stages T1 (205 men), T2 (256 men), T3 (239 men), and T4 (7 men), receiving definitive external radiation as sole therapy, was evaluated using univariate and multivariate techniques. Results: At a mean follow-up of 31 months, 157 patients (22%) developed relapse or a rising PSA. Multivariate analysis revealed pretreatment PSA level to be the most significant prognostic factor, with lesser though significant contributions due to Gleason grade (2-6 vs. 7-10) and transurethral resection in (T3(T4)) disease. The following four prognostic groupings were defined: group I, PSA {<=} 4 ng/ml, any grade; group II, 4 < PSA {<=} 20, grades 2-6; group III, 4 < PSA {<=} 20, grades 7-10; group IV, PSA > 20, any grade. Five-year actuarial relapse rates in these groups were: I, 12%; II, 34%; III, 40%; and IV, 81%. Posttreatment nadir PSA was an independent determinant of outcome and only patients with nadir values < 1 ng/ml fared well (5-year relapse rate 20%). Using rising PSA as an endpoint the 461 patients with (T1(T2)) disease had an actuarial freedom from disease rate of 70% at 5 years, which appeared to plateau, suggesting that many were cured. No plateau was evident for (T3(T4)) disease. Conclusion: Pretreatment serum PSA is the single most important predictor of disease outcome after radiation for local prostate cancer. Tumor grade has a lesser though significant prognostic role. Postirradiation nadir PSA value during the first year is a sensitive indicator of response to treatment. Only nadir values < 1 ng/ml are associated with a favorable outlook. A significant fraction of men with (T1(T2

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Freedland, Stephen J., E-mail: steve.freedland@duke.edu [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Gerber, Leah [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S. [Myriad Genetics, Inc, Salt Lake City, Utah (United States); Salama, Joseph K. [Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Stone, Steven [Myriad Genetics, Inc, Salt Lake City, Utah (United States)

2013-08-01

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

International Nuclear Information System (INIS)

Freedland, Stephen J.; Gerber, Leah; Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S.; Salama, Joseph K.; Stone, Steven

2013-01-01

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy

Perceived causes of prostate cancer among prostate cancer survivors in the Netherlands

NARCIS (Netherlands)

Kok, D.E.G.; Cremers, R.G.H.M.; Aben, K.K.H.; Oort, van I.M.; Kampman, E.; Kiemeney, L.A.L.M.

2013-01-01

Introduction The aim of this study was to evaluate self-reported causes of prostate cancer among prostate cancer survivors in the Netherlands to obtain insight into the common beliefs and perceptions of risk factors for prostate cancer. Materials and methods A total of 956 prostate cancer survivors,

To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

International Nuclear Information System (INIS)

Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda; Jia, William; Rennie, Paul S.

2011-01-01

Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge

To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

Energy Technology Data Exchange (ETDEWEB)

Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Jia, William [Department of Surgery and Brain Research Centre, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Rennie, Paul S., E-mail: prennie@interchange.ubc.ca [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada)

2011-03-24

Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

Directory of Open Access Journals (Sweden)

Paul S. Rennie

2011-03-01

Full Text Available Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i the PI3K/Akt pathway, (ii receptor tyrosine kinases, (iii the p38 MAPK pathway, and (iv the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

Genomic Basis of Prostate Cancer Health Disparity Among African-American Men

Science.gov (United States)

2013-07-01

prostatectomy or radiation therapy, the risk of metastasis is reduced, but erectile dysfunction, urinary incontinence , and rectal bleeding may occur...or radiation therapy, the risk of metastasis is reduced, but erectile dysfunction, urinary incontinence and rectal bleeding may occur, affecting the...ProstateCancer/index. 2. Dash A, Lee P, Zhou Q, Jean-Gilles J, Taneja S, Satagopan J, et al. Impact of socioeconomic factors on prostate cancer

3D Registration of mpMRI for Assessment of Prostate Cancer Focal Therapy.

Science.gov (United States)

Orczyk, Clément; Rosenkrantz, Andrew B; Mikheev, Artem; Villers, Arnauld; Bernaudin, Myriam; Taneja, Samir S; Valable, Samuel; Rusinek, Henry

2017-12-01

This study aimed to assess a novel method of three-dimensional (3D) co-registration of prostate magnetic resonance imaging (MRI) examinations performed before and after prostate cancer focal therapy. We developed a software platform for automatic 3D deformable co-registration of prostate MRI at different time points and applied this method to 10 patients who underwent focal ablative therapy. MRI examinations were performed preoperatively, as well as 1 week and 6 months post treatment. Rigid registration served as reference for assessing co-registration accuracy and precision. Segmentation of preoperative and postoperative prostate revealed a significant postoperative volume decrease of the gland that averaged 6.49 cc (P = .017). Applying deformable transformation based on mutual information from 120 pairs of MRI slices, we refined by 2.9 mm (max. 6.25 mm) the alignment of the ablation zone, segmented from contrast-enhanced images on the 1-week postoperative examination, to the 6-month postoperative T2-weighted images. This represented a 500% improvement over the rigid approach (P = .001), corrected by volume. The dissimilarity by Dice index of the mapped ablation zone using deformable transformation vs rigid control was significantly (P = .04) higher at the ablation site than in the whole gland. Our findings illustrate our method's ability to correct for deformation at the ablation site. The preliminary analysis suggests that deformable transformation computed from mutual information of preoperative and follow-up MRI is accurate in co-registration of MRI examinations performed before and after focal therapy. The ability to localize the previously ablated tissue in 3D space may improve targeting for image-guided follow-up biopsy within focal therapy protocols. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Functional roles for Rad9 in prostate cancer

International Nuclear Information System (INIS)

Lieberman, H.B.; Broustas, C.G.

2012-01-01

The goal of this work is to understand the mechanistic relationship between high levels of Rad9 protein and prostate cancer. The study is based on several findings suggesting a role for Rad9 in this disease. Rad9 has all the hallmark features of an oncogene or tumor suppressor. It regulates genomic stability, multiple cell cycle checkpoints, apoptosis and DNA repair. In addition, it can transactivate downstream target genes via direct interaction with promoter DNA sequences. We found Rad9 protein levels were very high in prostate cancer cell lines. Furthermore, we examined 52 primary normal prostate and 339 prostate cancer specimens for Rad9 protein by immunohistochemical staining. Statistical significance for Rad9 positive staining versus cancer, and stain intensity versus Stage were tested. We get a p-value of <0.001 when comparing percentage positive by cancer Stage, or stain intensity by cancer Stage. Based on these data, we sought to define the nature of the relationship between Rad9 and prostate cancer. We demonstrate that Rad9 acts as an oncogene in prostate cancer by playing a critical role in tumor formation in a mouse xenograph model. We also show that Rad9 is important for cellular phenotypes essential for metastasis, including tumor cell migration, invasion and resistance to programmed cell death after detachment from extracellular matrix. Therefore, Rad9 is critical for several aspects of prostate tumor progression, and could serve as a novel target for anti-cancer therapy

Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy.

Science.gov (United States)

Hvid, Thine; Winding, Kamilla; Rinnov, Anders; Dejgaard, Thomas; Thomsen, Carsten; Iversen, Peter; Brasso, Klaus; Mikines, Kari J; van Hall, Gerrit; Lindegaard, Birgitte; Solomon, Thomas P J; Pedersen, Bente K

2013-10-01

Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (PBody weight (Pbody fat mass (FM) (Pbody mass (P=0.99) was unchanged. Additionally, reductions were observed in abdominal (Pcancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men.

Planning and implementing an implanted fiducial programme for prostate cancer radiation therapy

International Nuclear Information System (INIS)

Thompson, A.; Owen, R.; Laferlita, M.; Fox, C.; Foroudi, F.; Tai, K. H.; Styles, C.

2008-01-01

Full text: Using implanted gold seeds as fiducial markers to verify the position of the prostate in radiation therapy is well accepted and is becoming the standard of practice and requirement for international multicentre trials. In 2006 the decision was made at the Peter MacCallum Caner Centre (Peter Mac) to plan for and implement this process as standard clinical practice for radical dose prostate treatments (74-78 Gy). Before this, programme verification of field placement for prostate cancer radiation treatment was routinely carried out using regular off-line electronic portal imaging with matching of bony anatomy. A small multidisciplinary team investigated and assisted in the implementation of this new practice across the Peter Mac sites at East Melbourne and our three satellite centres. Issues considered included seed size, number and position in the prostate, implant equipment, imaging equipment and procedure and consent and information forms. The use of a custom made fiducial pack, comprehensive patient information and a daily on-line imaging process was implemented. The experience of the first 28 patients at Peter Mac from January 2007 to May 2007 inclusive is reported on.

Dosimetric impact of mixed-energy volumetric modulated arc therapy plans for high-risk prostate cancer

Directory of Open Access Journals (Sweden)

Shyam Pokharel

2013-10-01

Full Text Available Purpose: This study investigated the dosimetric impact of mixing low and high energy treatment plans for prostate cancer treated with volumetric modulated arc therapy (VMAT technique in the form of RapidArc.Methods: A cohort of 12 prostate cases involving proximal seminal vesicles and lymph nodes was selected for this retrospective study. For each prostate case, the single-energy plans (SEPs and mixed-energy plans (MEPs were generated.  First, the SEPs were created using 6 mega-voltage (MV energy for both the primary and boost plans. Second, the MEPs were created using 16 MV energy for the primary plan and 6 MV energy for the boost plan. The primary and boost MEPs used identical beam parameters and same dose optimization values as in the primary and boost SEPs for the corresponding case. The dosimetric parameters from the composite plans (SEPs and MEPs were evaluated. Results: The dose to the target volume was slightly higher (on average <1% in the SEPs than in the MEPs. The conformity index (CI and homogeneity index (HI values between the SEPs and MEPs were comparable. The dose to rectum and bladder was always higher in the SEPs (average difference up to 3.7% for the rectum and up to 8.4% for the bladder than in the MEPs. The mean dose to femoral heads was higher by about 0.8% (on average in the MEPs than in the SEPs. The number of monitor units and integral dose were higher in the SEPs compared to the MEPs by average differences of 9.1% and 5.5%, respectively.Conclusion: The preliminary results from this study suggest that use of mixed-energy VMAT plan for high-risk prostate cancer could potentially reduce the integral dose and minimize the dose to rectum and bladder, but for the higher femoral head dose.-----------------------------------------------Cite this article as:Pokharel S. Dosimetric impact of mixed-energy volumetric modulated arc therapy plans for high-risk prostate cancer. Int J Cancer Ther Oncol 2013;1(1:01011.DOI: http

Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae [Kyungpook National University Medical Center and School of Medicine, Daegu (Korea, Republic of)

2016-03-15

This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV{sub max} and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV{sub max} were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV{sub max} was 4.7. In 16 patients who underwent follow-up PET/CT, SUV{sub max} was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment.

Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

Directory of Open Access Journals (Sweden)

Meacham Randall B

2010-06-01

Full Text Available Abstract Background Prostate-derived Ets factor (PDEF is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF in prostate cancer. Results We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression

Fully Automated Volumetric Modulated Arc Therapy Plan Generation for Prostate Cancer Patients

International Nuclear Information System (INIS)

Voet, Peter W.J.; Dirkx, Maarten L.P.; Breedveld, Sebastiaan; Al-Mamgani, Abrahim; Incrocci, Luca; Heijmen, Ben J.M.

2014-01-01

Purpose: To develop and evaluate fully automated volumetric modulated arc therapy (VMAT) treatment planning for prostate cancer patients, avoiding manual trial-and-error tweaking of plan parameters by dosimetrists. Methods and Materials: A system was developed for fully automated generation of VMAT plans with our commercial clinical treatment planning system (TPS), linked to the in-house developed Erasmus-iCycle multicriterial optimizer for preoptimization. For 30 randomly selected patients, automatically generated VMAT plans (VMAT auto ) were compared with VMAT plans generated manually by 1 expert dosimetrist in the absence of time pressure (VMAT man ). For all treatment plans, planning target volume (PTV) coverage and sparing of organs-at-risk were quantified. Results: All generated plans were clinically acceptable and had similar PTV coverage (V 95%  > 99%). For VMAT auto and VMAT man plans, the organ-at-risk sparing was similar as well, although only the former plans were generated without any planning workload. Conclusions: Fully automated generation of high-quality VMAT plans for prostate cancer patients is feasible and has recently been implemented in our clinic

Disease volume and distribution as drivers of treatment decisions in metastatic prostate cancer: From chemohormonal therapy to stereotactic ablative radiotherapy of oligometastases.

Science.gov (United States)

Saluja, Ronak; Cheung, Patrick; Zukotynski, Katherine; Emmenegger, Urban

2016-05-01

The prognosis of men with metastatic, castration-sensitive prostate cancer (CSPC) depends on both the distribution and extent of metastases, among other things. Patients with low-volume or oligometastatic disease have improved survival compared with those with high-volume metastases. While chemohormonal therapy is the new standard of care for men with high-volume metastatic CSPC, stereotactic ablative radiotherapy (SABR) is emerging as a promising treatment option with low toxicity for the management of oligometastatic CSPC. Our review summarizes the current evidence on the role of SABR in oligometastatic prostate cancer. SABR shows control rates of metastases ranging from 88% to 100% at 6 months to 3 years, and progression-free survival commonly reported as >50% for the first 12 months. In addition, SABR may allow androgen-deprivation therapy to be delayed by more than 2 years in selected patients, minimizing the chronic side effects associated with such therapy. However, much still needs to be learned before SABR can be implemented as standard treatment for oligometastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Positron emission tomography/computed tomography and radioimmunotherapy of prostate cancer

DEFF Research Database (Denmark)

Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

2009-01-01

of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, which targets the extracellular domain of prostate-specific membrane antigen, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. SUMMARY: PET......PURPOSE OF REVIEW: Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computed tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) as no effective therapies...... are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. RECENT FINDINGS: Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated...

Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

International Nuclear Information System (INIS)

Koontz, Bridget F.; Quaranta, Brian P.; Pura, John A.; Lee, W.R.; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S.; Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W.

2013-01-01

Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes

Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Koontz, Bridget F., E-mail: Bridget.Koontz@duke.edu [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Quaranta, Brian P. [21st Century Oncology, Asheville, North Carolina (United States); Pura, John A. [Division of Biostatistics, Duke Cancer Institute, Durham, North Carolina (United States); Lee, W.R.; Vujaskovic, Zeljko [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Gerber, Leah [Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States); Haake, Michael [Southeast Radiation Oncology, Charlotte, North Carolina (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Robertson, Cary N.; Polascik, Thomas J.; Moul, Judd W. [Department of Surgery, Duke Cancer Institute, Durham, North Carolina (United States); Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina (United States)

2013-09-01

Purpose: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Methods and Materials: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. Results: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Conclusions: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

A case report of monitoring PSA level changes in two prostate cancer patients treated with Mountain Ginseng Pharmacopuncture and Sweet Bee Venom along with western anticancer therapy

Directory of Open Access Journals (Sweden)

Yeonhee Lee

2011-12-01

Full Text Available Objectives: The purpose of this report is to find out how Mountain Ginseng Pharmacopuncture(MGP and Sweet Bee Venom(SBV treatments are effective on prostate cancer patients by monitoring Prostate specific antigen(PSA values. Methods: We treated two prostate cancer patients with MGP and SBV from October 2008 to April 2011. One patient had localized prostate cancer, the other was in the terminal stage of prostate cancer with lung and bone metastasis and both had been receiving western anticancer therapy. We had monitored the changes of PSA value. Results: In case 1, MGP and SBV treatments seemed to be helpful in preventing the recurrence of localized prostate cancer. In case 2, PSA value was decreased by MGP treatment. Conclusions: It is conceivable that MGP and SBV are effective treatments for patients with prostate cancer.

Molecular Biomarkers in the Clinical Management of Prostate Cancer.

Science.gov (United States)

Udager, Aaron M; Tomlins, Scott A

2018-01-08

Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

Science.gov (United States)

Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

Hit by waves-living with local advanced or localized prostate cancer treated with endocrine therapy or under active surveillance.

Science.gov (United States)

Ervik, Bente; Nordøy, Tone; Asplund, Kenneth

2010-01-01

Previous studies of living with prostate cancer have shown that the illness and the treatment cause physical as well as psychosocial problems. The aim of this study was to illuminate men's experiences living with localized or local advanced prostate cancer when curative treatment such as surgery or radiation therapy is not an option at the time of diagnosis. The study was conducted via qualitative interviews, using a phenomenological hermeneutic approach. Ten men treated with endocrine therapy or under active surveillance were interviewed. Being diagnosed with prostate cancer was described as a shock, with different aspects of the illness revealed gradually. The limited amount of time available for meeting with health care providers contributed to patients' feelings of being left alone with difficulty getting information and help. Sexual and urinary problems were perceived as a threat to their manhood. The spouses provided the closest everyday support. The life situation of these patients can be understood as living in a "state of readiness," expecting something to happen regarding their illness, and not always knowing where to get help. The results confirm existing knowledge of patient's experiences in living with prostate cancer regarding the initial shock perceived by the patients, the bodily alterations, and the important role of their spouses. Nurses, as well as general practitioners, must play a more active role in follow-up to ensure that the men and their spouses receive better help and support.