Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

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Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

Pubertal development and prostate cancer risk

DEFF Research Database (Denmark)

Bonilla, Carolina; Lewis, Sarah J; Martin, Richard M

2016-01-01

, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.......BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain...... to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI...

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

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Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Management of low (favourable)-risk prostate cancer.

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Carter, H Ballentine

2011-12-01

What's known on the subject? and What does the study add? Most men who are diagnosed with favourable-risk prostate cancer undergo some form of active intervention, despite evidence that treatment will not improve health outcomes for many. The decision to undergo treatment after diagnosis is, in part, related to the inability to precisely determine the long-term risk of harm without treatment. Nevertheless, physicians should consider patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments, before recommending a management option. This is especially important for older men, given the high level of evidence that those with low-risk disease are unlikely to accrue any benefit from curative intervention. What is known on the subject: Over treatment of favourable-risk prostate cancer is common, especially among older men. What does the study add: A review of the natural history of favourable-risk prostate cancer in the context of choices for management of the disease. • The management of favourable-risk prostate cancer is controversial, and in the absence of controlled trials to inform best practice, choices are driven by personal beliefs with resultant wide variation in practice patterns. • Men with favourable-risk prostate cancer diagnosed today often undergo treatments that will not improve overall health outcomes. • A shared-decision approach for selecting optimal management of favourable-risk disease should account for patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments. © 2011 THE AUTHOR. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Body mass index influences prostate cancer risk at biopsy in Japanese men.

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Masuda, Hitoshi; Kagawa, Makoto; Kawakami, Satoru; Numao, Noboru; Matsuoka, Yoh; Yokoyama, Minato; Yamamoto, Shinya; Yonese, Junji; Fukui, Iwao; Kihara, Kazunori

2013-07-01

To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m(2) ) as follows: body mass index and prostate cancer risk at biopsy, with an increased risk observed in men whose body mass index was ≥27.0 compared with the reference group. A significantly increased risk starting at body mass index ≥25.0 was found in high-grade disease. In contrast to our results, there has been no reported increase in the risk of prostate cancer at biopsy in Caucasians within the overweight range (body mass index of 25.0-29.9 based on World Health Organization classification). Japanese men within the overweight body mass index range who have an elevated prostate-specific antigen level also have a significant risk of harboring prostate cancer, especially high-grade disease. Overweight Japanese might be at greater prostate cancer risk at biopsy than overweight Caucasians. © 2012 The Japanese Urological Association.

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

Directory of Open Access Journals (Sweden)

Shakespeare TP

2016-05-01

Full Text Available Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Rural Clinical School, Faculty of Medicine, University of New South Wales, Coffs Harbour, NSW, Australia Aim: Both dose-escalated external beam radiotherapy (DE-EBRT and androgen deprivation therapy (ADT improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods: Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results: In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion: There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. Keywords: radiotherapy, IMRT, dose

High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

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Keisei Okamoto

2017-02-01

Full Text Available Purpose : To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR brachytherapy in combination with external beam radiotherapy (EBRT and short-term androgen deprivation therapy (ADT. Material and methods : From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT. The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%, 61 patients with 2 high-risk factors (43%, and 22 patients with 3 high-risk factors (15% including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results : Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS rate of 97.2%, and an overall survival (OS rate of 95.5%. Conclusions : High-dose (BED ≥ 220 Gy radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further.

[Fish intake and risk of prostate cancer].

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Dybkowska, Ewa; Świderski, Franciszek; Waszkiewicz-Robak, Bożena

2014-10-17

The aim of the study was to present the current state of knowledge concerning the relationship between the consumption of fish as materials rich in long chain polyunsaturated fatty acids (LC PUFA) omega-3, and the risk of prostate cancer. Many scientific reports confirm the health benefits from the consumption of fish and protective properties of LC PUFA omega-3 in relation to prostate cancer. However, there are reports that indicate a relationship of the high consumption of PUFA with the risk of prostate cancer. The way of processing and preservation of the fish, and other factors not included in previous studies, could have some importance in the etiology of this disease. High susceptibility of PUFA to oxidation changes and the technological fish processing (smoking, high-temperature cooking methods) contribute to the formation of many compounds, such as polycyclic aromatic hydrocarbons and heterocyclic amines - which may influence the formation of cancers - including prostate cancer. It is necessary to ensure an adequate amount of LC PUFA omega-3 in the diet through the consumption of proper quality fish and fish oils. Particular attention should be paid to the high susceptibility of PUFA to the oxidative processes, and the method of processing, preservation and storage of fish. Also pollution from the environment can significantly reduce the impact of health benefits of PUFA and fish, and even be the cause of cancers, including prostate cancer. Further research in this area should be more targeted to assess the impact of nutritional factors for the development of such tumors.

Fish intake and risk of prostate cancer

Directory of Open Access Journals (Sweden)

Ewa Dybkowska

2014-10-01

Full Text Available The aim of the study was to present the current state of knowledge concerning the relationship between the consumption of fish as materials rich in long chain polyunsaturated fatty acids (LC PUFA omega-3, and the risk of prostate cancer. Many scientific reports confirm the health benefits from the consumption of fish and protective properties of LC PUFA omega-3 in relation to prostate cancer. However, there are reports that indicate a relationship of the high consumption of PUFA with the risk of prostate cancer. The way of processing and preservation of the fish, and other factors not included in previous studies, could have some importance in the etiology of this disease. High susceptibility of PUFA to oxidation changes and the technological fish processing (smoking, high-temperature cooking methods contribute to the formation of many compounds, such as polycyclic aromatic hydrocarbons and heterocyclic amines – which may influence the formation of cancers – including prostate cancer. It is necessary to ensure an adequate amount of LC PUFA omega-3 in the diet through the consumption of proper quality fish and fish oils. Particular attention should be paid to the high susceptibility of PUFA to the oxidative processes, and the method of processing, preservation and storage of fish. Also pollution from the environment can significantly reduce the impact of health benefits of PUFA and fish, and even be the cause of cancers, including prostate cancer. Further research in this area should be more targeted to assess the impact of nutritional factors for the development of such tumors.

Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

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Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

2016-07-01

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. © 2016 UICC.

Polyunsaturated fatty acids and prostate cancer risk

DEFF Research Database (Denmark)

Khankari, Nikhil K; Murff, Harvey J; Zeng, Chenjie

2016-01-01

BACKGROUND: Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations...... and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men ...-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men

Pre-treatment risk stratification of prostate cancer patients: A critical review.

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Rodrigues, George; Warde, Padraig; Pickles, Tom; Crook, Juanita; Brundage, Michael; Souhami, Luis; Lukka, Himu

2012-04-01

The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems. A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema. The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and high-intermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

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Chen, Yu-Wei [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nezolosky, Michelle [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Den, Robert B. [Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States)

2016-03-15

Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95-0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test P=.0005; AHR: 0.91, 95% CI: 0.86-0.96, P=.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

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De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

2018-07-01

To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P PSA returned to normal values (PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

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

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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

Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone.

Science.gov (United States)

Agarwal, Harsh K; Mertan, Francesca V; Sankineni, Sandeep; Bernardo, Marcelino; Senegas, Julien; Keupp, Jochen; Daar, Dagane; Merino, Maria; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

2017-01-01

To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm 2 ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm 2 were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm 2 ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm 2 (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm 2 . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm 2 . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm 2 . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm 2 . 4 J. Magn. Reson. Imaging 2017;45:125-131. © 2016 International Society for Magnetic Resonance in Medicine.

Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

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Stella Koutros

Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

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

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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.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

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Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and

Estrogen receptor alpha polymorphisms and the risk of prostate cancer development.

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Jurečeková, Jana; Babušíková, Eva; Kmeťová, Monika; Kliment, Ján; Dobrota, Dušan

2015-11-01

The main purpose of the study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, rs2077647 and rs3798577, on the development of prostate cancer, their correlation with selected clinical characteristics, as well as consideration of potential interactions between four estrogen receptor alpha polymorphisms (rs2077647, rs3798577, PvuII, XbaI). The study was performed using 395 patients with histologically verified prostate cancer and 253 healthy male controls. The CC genotype of rs2077647 was significantly associated with prostate cancer (OR = 1.61). No association was found between rs3798577 polymorphism and prostate cancer. After stratification of patients according to the age at diagnosis and Gleason score, we observed significant correlation between rs2077647 polymorphism and prostate cancer risk in patients diagnosed before the age of 60 as well as patients with Gleason score prostate cancer risk development in patients older than 60 and with Gleason score ≥7. Double analysis of each combination of four studied polymorphisms showed that presence of at least three variant alleles was associated with prostate cancer risk in all combinations, while each containing rs3798577 was significantly associated with development of high-grade carcinomas. The present study suggests that rs2077647 polymorphism may be a risk factor for prostate cancer especially in patients diagnosed before the age of 60, while rs3798577 polymorphism could probably serve rather as promoting factor in combination with other polymorphisms in estrogen receptor alpha contributing preferably to development of high-grade carcinomas.

Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort

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Larsen, Signe Benzon; Brasso, Klaus; Iversen, Peter

2013-01-01

Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer.......Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer....

Intratumoural evolutionary landscape of high-risk prostate cancer: The PROGENY study of genomic and immune parameters

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Linch, M.; Goh, G.; Hiley, C.

2017-01-01

Background: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-...

Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

NARCIS (Netherlands)

Oort, van I.M.; Witjes, J.A.; Kok, D.E.G.; Kiemeney, L.A.; Hulsbergen-van de Kaa, C.A.

2008-01-01

Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate

Childhood height, adult height, and the risk of prostate cancer

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Bjerregaard, Lise Geisler; Aarestrup, Julie; Gamborg, Michael

2016-01-01

PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect...... on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained...... through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk...

Prostate Cancer Risk Prediction Models

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Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

BPH and prostate cancer risk

Directory of Open Access Journals (Sweden)

Saiful Miah

2014-01-01

Full Text Available Introduction: With the exclusion of non-melanomatous skin malignancy, prostate cancer (PCa is the second most prevalent cancer in men globally. It has been reported that the majority of men will develop benign prostatic hyperplasia (BPH by the time they reach their 60s. Together, these prostatic diseases have a significant morbidity and mortality affecting over a billion men throughout the world. The risk of developing prostate cancer of men suffering BPH is one that has resulted in a healthy debate amongst the urological community. Here, we try to address this conundrum with clinical and basic science evidence. Materials and Methods: Data from an online search and contemporary data presented at international urological congresses was reviewed. Results: BPH and PCa can be linked together at a molecular and cellular level on genetic, hormonal, and inflammatory platforms suggesting that these prostatic diseases have common pathophysiological driving factors. Epidemiological studies are weighted towards the presence of BPH having a greater risk for a man to develop PCa in his lifetime; however, a conclusion of causality cannot be confidently stated. Conclusion: The future workload healthcare practitioners will face regarding BPH, and PCa will substantially increase. Further basic science and large epidemiological studies using a global cohort of men are required prior to the urological community confidently counseling their patients with BPH with regards to their PCa risk.

BPH and prostate cancer risk.

Science.gov (United States)

Miah, Saiful; Catto, James

2014-04-01

With the exclusion of non-melanomatous skin malignancy, prostate cancer (PCa) is the second most prevalent cancer in men globally. It has been reported that the majority of men will develop benign prostatic hyperplasia (BPH) by the time they reach their 60s. Together, these prostatic diseases have a significant morbidity and mortality affecting over a billion men throughout the world. The risk of developing prostate cancer of men suffering BPH is one that has resulted in a healthy debate amongst the urological community. Here, we try to address this conundrum with clinical and basic science evidence. Data from an online search and contemporary data presented at international urological congresses was reviewed. BPH and PCa can be linked together at a molecular and cellular level on genetic, hormonal, and inflammatory platforms suggesting that these prostatic diseases have common pathophysiological driving factors. Epidemiological studies are weighted towards the presence of BPH having a greater risk for a man to develop PCa in his lifetime; however, a conclusion of causality cannot be confidently stated. The future workload healthcare practitioners will face regarding BPH, and PCa will substantially increase. Further basic science and large epidemiological studies using a global cohort of men are required prior to the urological community confidently counseling their patients with BPH with regards to their PCa risk.

Selenium status and risk of prostate cancer in a Danish population

DEFF Research Database (Denmark)

Outzen, Malene; Tjønneland, Anne; Larsen, Erik Huusfeldt

2016-01-01

Low-Se status may be associated with a higher risk of notably advanced prostate cancer. In a Danish population with a relatively low Se intake, we investigated the association between pre-diagnostic Se status and (1) the risk of total, advanced and high-grade prostate cancer and (2) all-cause and...

Radiotherapy and androgen ablation for clinically localized high-risk prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Pollack, Alan; Zagars, Gunar K; Kopplin, Susan

1995-04-30

Purpose: The response of patients with clinical stages T1-4 prostate cancer to radiotherapy is variable. A particularly poor prognostic group has been found to be comprised of those with pretreatment prostate specific antigen (PSA) levels above 30 ng/ml with any tumor grade, or PSA levels > 10 and {<=} 30 with tumors grade 3 or 4. These patients have over an 80% actuarial risk of biochemical failure 3 years after definitive external beam radiotherapy. Thus, patients with these high-risk features require more aggressive therapy. During the last 3-4 years, the policy to treat such patients with radiotherapy and androgen ablation (XRT/HORM) was instituted. A retrospective comparison was made between high-risk patients treated with radiotherapy alone (XRT) vs. XRT/HORM. Methods and Materials: Between 1987 and 1991, there were 81 high-risk patients treated with XRT. There were 38 high-risk patients treated with XRT/HORM between 1990 and 1992. The median follow-up was 37 months for the XRT group and 22 months for the XRT/HORM group. No patient had clinical, radiographic, or pathologic evidence of lymph node involvement. The median dose to the prostate was 66 Gy for the XRT group and 68 Gy for the XRT/HORM group. Results: The distributions of several potential prognostic factors were analyzed. Significant differences between the groups were observed for tumor grade, pretreatment prostatic acid phosphatase, and age. The XRT/HORM group was composed of patients with worse features, including a greater proportion of patients with grade 4 tumors, more with abnormal acid phosphatase levels, and more under 60 years of age. The actuarial incidence of a rising PSA at 3 years for the XRT group was 81% vs. 15% for the XRT/HORM group (p < 0.0001). In addition, local relapse at 3 years was 34% for the XRT group and 15% for the XRT/HORM group (p < 0.02). There was no difference between the groups in terms of survival. Cox proportional hazards analyses were performed using several

Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

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Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

2003-05-07

Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

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Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

2014-11-01

Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

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Hall, Michael J; Ruth, Karen J; Chen, David Yt; Gross, Laura M; Giri, Veda N

2015-01-01

Advancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population. Consecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy. Knowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016). Knowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.

Inflammatory Genetic Markers of Prostate Cancer Risk

International Nuclear Information System (INIS)

Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.

2010-01-01

Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

Inflammatory Genetic Markers of Prostate Cancer Risk

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Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

2010-06-08

Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

Physical activity and risk of prostate and bladder cancer in China: The South and East China case-control study on prostate and bladder cancer.

Directory of Open Access Journals (Sweden)

Raoul C Reulen

Full Text Available Recent meta-analyses have suggested a modest protective effect of high levels of physical activity on developing both prostate and bladder cancer, but significant heterogeneity between studies included in these meta-analyses existed. To our knowledge, few Chinese studies investigated the association between physical activity and prostate cancer and none between physical activity and bladder cancer. Given the inconsistencies between previous studies and because studies on the relation between physical activity and prostate and bladder cancer in China are scarce, it remains elusive whether there is a relationship between physical activity and prostate and bladder cancer within the Chinese population.We investigated the association between physical activity and risk of developing prostate and bladder cancer within a hospital-based case-control study in the East and South of China among 260 and 438 incident prostate and bladder cancer cases, respectively, and 427 controls. A questionnaire was administered to measure physical activity as metabolic equivalents (METs. Random effects logistic regression was used to calculate odds ratios (ORs of prostate and bladder cancer for different levels of physical activity and for the specific activities of walking and cycling.Increasing overall physical activity was associated with a significant reduction in prostate cancer risk (Ptrend = 0.04 with the highest activity tertile level showing a nearly 50% reduction in prostate cancer risk (OR = 0.53, 95%CI: 0.28-0.98. Overall physical activity was not significantly associated with risk of bladder cancer (Ptrend = 0.61, neither were vigorous (Ptrend = 0.60 or moderate levels of physical activity (Ptrend = 0.21. Walking and cycling were not significantly associated with either prostate (Ptrend> = 0.62 or bladder cancer risk (Ptrend> = 0.25.The findings of this largest ever case-control study in China investigating the relationship between physical activity and

Validation of Association of Genetic Variants at 10q with PSA Levels in Men at High Risk for Prostate Cancer

Science.gov (United States)

Chang, Bao-Li; Hughes, Lucinda; Chen, David Y. T.; Gross, Laura; Ruth, Karen; Giri, Veda N.

2013-01-01

Objectives Men with a family history of prostate cancer and African American men are at increased risk for prostate cancer and stand to benefit from individualized interpretation of PSA to guide screening strategies. The purpose of this study was to validate six previously identified markers among high-risk men enrolled in the Prostate Cancer Risk Assessment Program - a prostate cancer screening study. Patients and Methods Eligibility for PRAP includes men ages 35–69 years with a family history of prostate cancer, any African American male regardless of family history, and men with known BRCA gene mutations. GWAS markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12), and rs17632542 (19q13.33). Genotyping methods included either Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders. Results 707 participants (37% Caucasian, 63% African American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) strongly associated with PSA levels among high-risk Caucasian participants (p<0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) demonstrated an association to PSA level (p=0.03) in high-risk Caucasian men, with a 15% increase in PSA with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 is proposed specific to high-risk Caucasian men. Conclusion Genetic variation at 10q may be particularly important in personalizing interpretation of PSA for high-risk Caucasian men. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for high-risk Caucasian men. Further study is warranted. PMID:23937305

Nutrition, hormones and prostate cancer risk: results from the European prospective investigation into cancer and nutrition.

Science.gov (United States)

Key, Timothy J

2014-01-01

Nutritional factors may influence the risk of developing prostate cancer, but understanding of this topic is poor. This chapter discusses research on this subject, mostly from the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort which includes 150,000 men recruited in the 1990s in eight European countries. So far the EPIC collaborators have published analyses of the relationship of prostate cancer risk with the intake of a range of foods and nutrients, and with blood-based markers of nutritional factors, on up to nearly 3,000 incident cases of prostate cancer. Most of the results of these analyses have been null, with no clear indication that the risk for prostate cancer is related to intakes of meat, fish, fruit, vegetables, fibre, fat or alcohol or with blood levels of fatty acids, carotenoids, tocopherols, B vitamins, vitamin D, or selenium. There is some evidence from EPIC that risk may be increased in men with a high intake of protein from dairy products, and analyses of hormone levels have shown that risk is higher in men with relatively high blood levels of insulin-like growth factor-I (IGF-I). More research is needed to better describe the relationships of prostate cancer risk with IGF-I and related hormones, and to better understand whether nutritional factors may influence risk through hormones or perhaps by other mechanisms.

Prostate cancer risk and recurrence: the role of nutrition and clinical aspects

NARCIS (Netherlands)

Kok, D.E.G.

2013-01-01

Background Prostate cancer is the most common cancer among men in Western countries. Knowledge on prostate cancer aetiology is required for identification of high-risk groups, optimization of treatment strategies, and development of prevention programs. The aim of this thesis

Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

International Nuclear Information System (INIS)

Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

2011-01-01

Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR] 0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

Vitamin D, Sunlight and Prostate Cancer Risk

Directory of Open Access Journals (Sweden)

Krishna Vanaja Donkena

2011-01-01

Full Text Available Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR, and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention.

Prostate cancer: The main risk and protective factors-Epigenetic modifications.

Science.gov (United States)

Adjakly, Mawussi; Ngollo, Marjolaine; Dagdemir, Aslihan; Judes, Gaëlle; Pajon, Amaury; Karsli-Ceppioglu, Seher; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

2015-02-01

With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

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Jacobs, Bruce L; Zhang, Yun; Schroeck, Florian R; Skolarus, Ted A; Wei, John T; Montie, James E; Gilbert, Scott M; Strope, Seth A; Dunn, Rodney L; Miller, David C; Hollenbeck, Brent K

2013-06-26

The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P risk of noncancer mortality (P use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95% CI, 24%-25%), or 244.2 per 1000 patients diagnosed with prostate cancer (P risk disease, high risk of noncancer mortality, or both, the use of

The 4q27 locus and prostate cancer risk

International Nuclear Information System (INIS)

Tindall, Elizabeth A; Hoang, Hoa N; Southey, Melissa C; English, Dallas R; Hopper, John L; Giles, Graham G; Severi, Gianluca; Hayes, Vanessa M

2010-01-01

Chronic inflammation is considered to be implicated in the development of prostate cancer. In this study we are the first to investigate a potential association between variants in an autoimmune related region on chromosome 4q27 and prostate cancer risk. This region harbors two cytokine genes IL-2 and the recently described IL-21. We genotyped six variants previously associated with autoimmune disease (namely rs13151961, rs13119723, rs17388568, rs3136534, rs6822844 and rs6840978) and one functional IL-2 promoter variant (rs2069762) for possible association with prostate cancer risk using the Australian Risk Factors for Prostate Cancer case-control Study. Overall, our results do not support an association between the seven variants at position 4q27 and prostate cancer risk. Per allele odds ratios (ORs) were not significantly different from 1 (all P-values = 0.06). However, we found suggestive evidence for a significant association between the presence of the rs13119723 variant (located in a protein of unknown function) and men with a family history of prostate cancer in first-degree relatives (P-value for interaction 0.02). The per allele OR associated with this variant was significantly higher than 1 (2.37; 95% C.I. = 1.01-5.57). We suggest that genetic variation within the chromosome 4q27 locus might be associated with prostate cancer susceptibility in men with a family history of the disease. Furthermore, our study alludes to a potential role of unknown protein KIAA1109 in conferring this risk

Saw palmetto supplement use and prostate cancer risk.

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Bonnar-Pizzorno, Raven M; Littman, Alyson J; Kestin, Mark; White, Emily

2006-01-01

Saw palmetto is an herb used to treat the symptoms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50-76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto-containing multivitamins over the previous 10 yr in addition to other information on supplement intake, medical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the western Washington Surveillance, Epidemiology, and End Results cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw palmetto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74-1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk.

Fracture risk in Danish men with prostate cancer

DEFF Research Database (Denmark)

Abrahamsen, Bo; Nielsen, Morten F; Eskildsen, Peter Claes

2007-01-01

To assess the risk of fracture attributable to prostate cancer, and the impact of exposure to prescribed gonadotrophin-releasing hormone agonists and antiandrogens on this risk in a nationwide, population-based case-control study.......To assess the risk of fracture attributable to prostate cancer, and the impact of exposure to prescribed gonadotrophin-releasing hormone agonists and antiandrogens on this risk in a nationwide, population-based case-control study....

The Early Result of Whole Pelvic Radiotherapy and Stereotactic Body Radiotherapy Boost for High Risk Localized Prostate Cancer

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Yu-Wei eLin

2014-10-01

Full Text Available PurposeThe rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer.Methods and MaterialsFrom October 2009 to August 2012, 41 patients of newly diagnosed, high-risk or very high-risk (NCCN definition localized prostate cancer patients were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45Gy (25 fractions of 1.8Gy. The SBRT boost dose was 21 Gy (three fractions of 7 Gy. Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI and genitourinary (GU tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0. Biochemical failure was defined by Phoenix definition.ResultsMedian follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow up, there was no grade 3 late GU or GI toxicity.ConclusionsWhole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles.

Neoadjuvant Treatment of High-Risk, Clinically Localized Prostate Cancer Prior to Radical Prostatectomy.

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Pietzak, Eugene J; Eastham, James A

2016-05-01

Multimodal strategies combining local and systemic therapy offer the greatest chance of cure for many with men with high-risk prostate cancer who may harbor occult metastatic disease. However, no systemic therapy combined with radical prostatectomy has proven beneficial. This was in part due to a lack of effective systemic agents; however, there have been several advancements in the metastatic and castrate-resistant prostate cancer that might prove beneficial if given earlier in the natural history of the disease. For example, novel hormonal agents have recently been approved for castration-resistant prostate cancer with some early phase II neoadjuvant showing promise. Additionally, combination therapy with docetaxel-based chemohormonal has demonstrated a profound survival benefit in metastatic hormone-naïve patients and might have a role in eliminating pre-existing ADT-resistant tumor cells in the neoadjuvant setting. The Cancer and Leukemia Group B (CALGB)/Alliance 90203 trial has finished accrual and should answer the question as to whether neoadjuvant docetaxel-based chemohormonal therapy provides an advantage over prostatectomy alone. There are also several promising targeted agents and immunotherapies under investigation in phase I/II trials with the potential to provide benefit in the neoadjuvant setting.

Bisphenol A and other environmental risk factors for prostate cancer in Hong Kong.

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Tse, Lap Ah; Lee, Priscilla Ming Yi; Ho, Wing Ming; Lam, Augustine Tsan; Lee, Man Kei; Ng, Simon Siu Man; He, Yonghua; Leung, Ka-Sing; Hartle, Jennifer C; Hu, Howard; Kan, Haidong; Wang, Feng; Ng, Chi Fai

2017-10-01

Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in Chinese, with special reference to bisphenol A (BPA). We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors. Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15-2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07-3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07-2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34-0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01-2.44). Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate. Copyright © 2017. Published by Elsevier Ltd.

Cadmium burden and the risk and phenotype of prostate cancer

International Nuclear Information System (INIS)

Chen, Yi-Chun; Pu, Yeong S; Wu, Hsi-Chin; Wu, Tony T; Lai, Ming Kuen; Yang, Chun Y; Sung, Fung-Chang

2009-01-01

Studies on the association between prostate cancer and cadmium exposure have yielded conflicting results. This study explored cadmium burden on the risk and phenotype of prostate cancer in men with no evident environmental exposure. Hospital-based 261 prostate cancer cases and 267 controls with benign diseases were recruited from four hospitals in Taiwan. Demographic, dietary and lifestyle data were collected by standardized questionnaires. Blood cadmium (BCd) and creatinine-adjusted urine cadmium (CAUCd) levels were measured for each participant. Statistical analyses measured the prostate cancer risk associated with BCd and CAUCd separately, controlling for age, smoking and institution. BCd and CAUCd levels within cases were compared in relation to the disease stage and the Gleason score. High family income, low beef intake, low dairy product consumption and positive family history were independently associated with the prostate carcinogenesis. There was no difference in BCd levels between cases and controls (median, 0.88 versus 0.87 μg/l, p = 0.45). Cases had lower CAUCd levels than controls (median, 0.94 versus 1.40 μg/g creatinine, p = 0.001). However, cases with higher BCd and CAUCd levels tended to be at more advanced stages and to have higher Gleason scores. The prostate cancer cases with Gleason scores of ≥ 8 had an odds ratio of 2.89 (95% confidence interval 1.25-6.70), compared with patients with scores of 2-6. Higher CAUCd and BCd levels may be associated with advanced cancer phenotypes, but there was only a tenuous association between cadmium and prostate cancer

Genetic association of the KLK4 locus with risk of prostate cancer.

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Felicity Lose

Full Text Available The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (± 10 kb in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥ 7 revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the P(trend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r(2 ≥ 0.98. Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality.

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Nutt, Max; Reed, Zachary; Köhler, Tobias S

2016-01-01

The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer. We explore articles that have shown the contrary (no link), explore the studies' strengths and weaknesses, describe possible prostate cancer pathophysiologic mechanisms, and apply Bradford Hill criteria to help discern correlation with causation. The risk and interest of association of prostate cancer with vasectomy has waxed and waned over the last three decades. Based on our review, vasectomy remains a safe form of sterilization and does not increase prostate cancer risk.

Occupational exposure to solar ultraviolet radiation and the risk of prostate cancer.

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Peters, Cheryl E; Demers, Paul A; Kalia, Sunil; Hystad, Perry; Villeneuve, Paul J; Nicol, Anne-Marie; Kreiger, Nancy; Koehoorn, Mieke W

2016-11-01

Preventable risk factors for prostate cancer are poorly understood; sun exposure is a possible protective factor. The goal of this study was to investigate prostate cancer risk in outdoor workers, a population with high sun exposure. Prostate cancer cases and controls from a large study (conducted between 1994 and 1997) were used for this analysis. A job exposure matrix (JEM) was used to assign solar ultraviolet radiation (UVR) at work as moderate (2 to hours outside/day) or high (≥6 hours). Average daily satellite UV-B measures were linked to the latitude/longitude of the residences of each participant. Several other exposure metrics were also examined, including ever/never exposed and standard erythemal dose by years (SED×years). Logistic regression was used to evaluate the association between solar UVR exposure and the odds of prostate cancer. A total of 1638 cases and 1697 controls were included. Men of Indian and Asian descent had reduced odds of prostate cancer (ORs 0.17 (0.08 to 0.35) and 0.25 (0.15 to 0.41), respectively) compared with Caucasian men, as did single men (OR 0.76 (0.58 to 0.98)) compared with married men. Overall, no statistically significant associations were observed between sun exposure and prostate cancer with 1 exception. In the satellite-enhanced JEM that considered exposure in high category jobs only, prostate cancer odds in the highest quartile of cumulative exposure was decreased compared with unexposed men (OR 0.68 (0.51 to 0.92)). This study found limited evidence for an association with prostate cancer, with the exception of 1 statistically significant finding of a decreased risk among workers with the longest term and highest sun exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

International Nuclear Information System (INIS)

Barkati, Maroie; Williams, Scott G.; Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat; Dyk, Sylvia van; See, Andrew; Duchesne, Gillian M.

2012-01-01

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable-risk

High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

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Barkati, Maroie [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Williams, Scott G., E-mail: scott.williams@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Dyk, Sylvia van [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); See, Andrew [Ballarat Austin Radiation Oncology Centre, Ballarat (Australia); Duchesne, Gillian M. [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia)

2012-04-01

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable-risk

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

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Cha, Eugene K; Eastham, James A

2015-05-01

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomarkers in Prostate Cancer Epidemiology

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Mudit Verma

2011-09-01

Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

Antibiotic and anti-inflammatory use and the risk of prostate cancer

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Bent Stephen

2009-04-01

Full Text Available Abstract Background Prostate inflammation or infection may increase the risk of prostate cancer. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs are used to treat prostatitis and urinary tract infections (UTIs. The objective of our study was to assess whether their use decreases the risk of prostate cancer. Methods We conducted a case-control study among men with incident prostate cancer (N = 65 cases and without prostate cancer (N = 195 controls at the San Francisco Veteran Affairs medical center (VAMC between June 1996 and June 2006. Cases were all patients who had prostate biopsies positive for cancer. We matched controls to cases on age group and race at a 3:1 ratio, and each matched pair was given an identical index date. Total antibiotic, aspirin, and NSAID use (number of prescriptions was computed for each participant by drug type and was restricted to a fill date at least 1 year before the index date. Logistic regression was used for analysis. We adjusted for the matching variables (age group and race and potential confounders (years of VAMC enrollment and number of clinic visits. Results Neither total antibiotic use nor total anti-inflammatory use reduces the risk of prostate cancer (P > 0.05. Conclusion Our analysis did not reveal a relation between use of antibiotics, aspirin, or NSAIDs and the risk of prostate cancer.

Combined 18F-Fluciclovine PET/MRI Shows Potential for Detection and Characterization of High-Risk Prostate Cancer.

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Elschot, Mattijs; Selnæs, Kirsten M; Sandsmark, Elise; Krüger-Stokke, Brage; Størkersen, Øystein; Giskeødegård, Guro F; Tessem, May-Britt; Moestue, Siver A; Bertilsson, Helena; Bathen, Tone F

2018-05-01

The objective of this study was to investigate whether quantitative imaging features derived from combined 18 F-fluciclovine PET/multiparametric MRI show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight patients diagnosed with high-risk prostate cancer underwent simultaneous 18 F-fluciclovine PET/MRI before radical prostatectomy. Volumes of interest (VOIs) for prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images, using histology as a reference. Tumor VOIs were marked as high-grade (≥Gleason grade group 3) or not. MRI and PET features were extracted on the voxel and VOI levels. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross-validation was performed to distinguish tumors from benign tissue (BPH, prostatitis, or healthy tissue) and high-grade tumors from other tissue (low-grade tumors or benign tissue). The performance levels of PET, MRI, and combined PET/MRI features were compared using the area under the receiver-operating-characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor VOIs (26 high-grade), 36 BPH VOIs, 6 prostatitis VOIs, and 37 healthy-tissue VOIs. PET/MRI performed better than MRI and PET alone for distinguishing tumors from benign tissue (AUCs of 87%, 81%, and 83%, respectively, at the voxel level and 96%, 93%, and 93%, respectively, at the VOI level) and high-grade tumors from other tissue (AUCs of 85%, 79%, and 81%, respectively, at the voxel level and 93%, 93%, and 91%, respectively, at the VOI level). T2-weighted MRI, diffusion-weighted MRI, and PET features were the most important for classification. Conclusion: Combined 18 F-fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. © 2018 by the Society of Nuclear Medicine and Molecular

Statin and NSAID Use and Prostate Cancer Risk

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Coogan, Patricia F.; Kelly, Judith Parsells; Strom, Brian L.; Rosenberg, Lynn

2010-01-01

Purpose Some studies have reported reduced risks of advanced, but not early, prostate cancer among statin users, and one study found a reduced risk only among statin users who had also used nonsteroidal anti-inflammatory drugs (NSAIDs). We have previously reported no association between statin use and prostate cancer in our hospital-based Case Control Surveillance Study. The purpose of the present analyses was to update the findings by cancer stage and to evaluate the joint use of statins and NSAIDs. Methods Cases were 1367 men with prostate cancer and controls were 2007 men with diagnoses unrelated to statin or NSAID use. We used multivariable logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for statin use compared with no use, and joint use of statin and NSAIDs compared with use of neither. Results The odds ratio among regular statin users was 1.1 (95% CI 0.9–1.5), and odds ratios were similar among early and late stage cancers. The odds ratio among joint statin and NSAID users was 1.1 (95% CI 0.7–1.6). Conclusion The present results do not support a protective effect of statin use, or statin and NSAID use, on the risk of advanced prostate cancer. PMID:20582910

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

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Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

2016-05-01

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

Serum insulin-like growth factor 1(IGF-I) and prostatic cancer risk a retrospective study

International Nuclear Information System (INIS)

Li Liren; Liu Jiumin; Lu Bailing

2001-01-01

Objective: To investigate the relationship between serum IGF-I levels and prostatic cancer. Methods: Serum IGF-I levels were determined by immunoradiometric assay (IRMA) in 30 cases of prostatic cancer, 30 cases of benign prostatic hyperplasia (BPH) and 30 healthy subjects as controls. Results: The mean levels of serum IGF-I in prostatic cancer (148 +- 49.6 μg/L) were significantly higher than those in BPH (91.0 +- 32.8 μg/L) and healthy subjects (105 +- 25.6 μg/L) (P 0.05). The IGF-I levels were not relates to BHP, but increased values of IGF-I were associated with increased risk of prostatic cancer. The odds ratio was 11.23 for patients of prostatic cancer compared with healthy subjects, (95 percent confidence interval 3.09 - 40.7). Conclusion: This finding suggests that high IGF-I may be associated with increase risk of prostate cancer in human

Oncological outcomes of high-risk prostate cancer patients between robot-assisted laparoscopic radical prostatectomy and laparoscopic radical prostatectomy in Taiwan

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Chieh-Chun Liao

2018-01-01

Full Text Available Objective: To compare pathological and oncological outcomes between robotic-assisted laparoscopic radical prostatectomy (RaLRP and laparoscopic radical prostatectomy (LRP among high-risk prostate cancer patient in a tertiary center in Taiwan. Materials and methods: From November 2003 to October 2013, 129 high-risk prostate cancer patients receiving minimally-invasive radical prostatectomy were included. The Kaplan–Meier analysis was used for measuring biochemical recurrence-free survival (BFS. Multivariate logistic regression models and Cox proportional hazards regression models were used to determine predictors of positive surgical margin and BFS. Results: Among the 129 high-risk prostate cancer patients included, 80 (62% patients received LRP and 49 (38% patients received RaLRP. There was no significant difference of positive surgical margin and biochemical recurrence rate between RaLRP and LRP group (P = 0.802 and 0.292. Higher pathological T stage predicted an increased likelihood of positive margins (OR = 3.44, 95% CI [1.45, 8.18], P = 0.005. Higher initial PSA level (HR = 2.88, 95% CI [1.04, 7.94], P = 0.041 and positive surgical margin (HR = 2.55, 95% CI [1.20, 5.44], P = 0.015 were poor prognostic factors for BFS. Conclusion: RaLRP can be considered among high-risk prostate cancer in Asian people with comparable oncological outcomes to LRP. Higher pathological T stage was associated with increased likelihood of positive margins, patients with higher iPSA level and positive surgical margin had worsen biochemical recurrence-free survival.

Risk factors for the onset of prostatic cancer: age, location, and behavioral correlates

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Leitzmann MF

2012-01-01

Full Text Available Michael F Leitzmann1, Sabine Rohrmann21Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany; 2Institute of Social and Preventive Medicine, University of Zurich, Zurich, SwitzerlandAbstract: At present, only three risk factors for prostate cancer have been firmly established; these are all nonmodifiable: age, race, and a positive family history of prostate cancer. However, numerous modifiable factors have also been implicated in the development of prostate cancer. In the current review, we summarize the epidemiologic data for age, location, and selected behavioral factors in relation to the onset of prostate cancer. Although the available data are not entirely consistent, possible preventative behavioral factors include increased physical activity, intakes of tomatoes, cruciferous vegetables, and soy. Factors that may enhance prostate cancer risk include frequent consumption of dairy products and, possibly, meat. By comparison, alcohol probably exerts no important influence on prostate cancer development. Similarly, dietary supplements are unlikely to protect against the onset of prostate cancer in healthy men. Several factors, such as smoking and obesity, show a weak association with prostate cancer incidence but a positive relation with prostate cancer mortality. Other factors, such as fish intake, also appear to be unassociated with incident prostate cancer but show an inverse relation with fatal prostate cancer. Such heterogeneity in the relationship between behavioral factors and nonadvanced, advanced, or fatal prostate cancers helps shed light on the carcinogenetic process because it discerns the impact of exposure on early and late stages of prostate cancer development. Inconsistent associations between behavioral factors and prostate cancer risk seen in previous studies may in part be due to uncontrolled detection bias because of current widespread use of prostate-specific antigen

Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer

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John, Esther M.; Stern, Mariana C.; Sinha, Rashmi; Koo, Jocelyn

2012-01-01

Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer. PMID:21526454

Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.

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Heaphy, Christopher M; Gaonkar, Gaurav; Peskoe, Sarah B; Joshu, Corinne E; De Marzo, Angelo M; Lucia, M Scott; Goodman, Phyllis J; Lippman, Scott M; Thompson, Ian M; Platz, Elizabeth A; Meeker, Alan K

2015-08-01

Telomeres are repetitive nucleoproteins that help maintain chromosomal stability by inhibiting exonucleolytic degradation, prohibiting inappropriate homologous recombination, and preventing chromosomal fusions by suppressing double-strand break signals. We recently observed that men treated for clinically localized prostate cancer with shorter telomeres in their cancer-associated stromal cells, in combination with greater variation in cancer cell telomere lengths, were significantly more likely to progress to distant metastases, and die from their disease. Here, we hypothesized that shorter stromal cell telomere length would be associated with prostate cancer risk at time of biopsy. Telomere-specific fluorescence in situ hybridization (FISH) analysis was performed in normal-appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N = 32) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N = 50), defined as negative for cancer on an end-of-study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell-to-cell telomere length variability, and risk of prostate cancer. Men with short stromal cell telomere lengths (below median) had 2.66 (95% CI 1.04-3.06; P = 0.04) times the odds of prostate cancer compared with men who had longer lengths (at or above median). Conversely, we did not observe statistically significant associations for short telomere lengths in normal-appearing basal (OR = 2.15, 95% CI 0.86-5.39; P= 0 .10) or luminal (OR = 1.15, 95% CI 0.47-2.80; P = 0.77) cells. These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential

Fatherhood status and risk of prostate cancer: nationwide, population-based case-control study.

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Wirén, Sara M; Drevin, Linda I; Carlsson, Sigrid V; Akre, Olof; Holmberg, Erik C; Robinson, David E; Garmo, Hans G; Stattin, Pär E

2013-08-15

Previous studies have shown a decreased risk of prostate cancer for childless men; however, the cause of the association remains to be elucidated. The aim of our study was to assess the risk of prostate cancer by fatherhood status, also considering potential confounding factors. In a case-control study in Prostate Cancer data Base Sweden 2.0, a nationwide, population-based cohort, data on number of children, marital status, education, comorbidity and tumor characteristics obtained through nationwide healthcare registers and demographic databases for 117,328 prostate cancer cases and 562,644 controls, matched on birth year and county of residence, were analyzed. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer overall and by risk category, adjusting for marital status and education. Childless men had a decreased risk of prostate cancer compared to fathers, OR = 0.83 (95% CI = 0.82-0.84), and risk was lower for low-risk prostate cancer, OR = 0.74 (95% CI = 0.72-0.77), than for metastatic prostate cancer, OR = 0.93 (95% CI = 0.90-0.97). Adjustment for marital status and education attenuated the association in the low-risk category, adjusted OR = 0.87 (95% CI = 0.84-0.91), whereas OR for metastatic cancer remained virtually unchanged, adjusted OR = 0.92 (95% CI = 0.88-0.96). Our data indicate that the association between fatherhood status and prostate cancer to a large part is due to socioeconomic factors influencing healthcare-seeking behavior including testing of prostate-specific antigen levels. Copyright © 2013 UICC.

Fatherhood status and risk of prostate cancer: Nationwide, population-based case–control study

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Wirén, Sara M; Drevin, Linda I; Carlsson, Sigrid V; Akre, Olof; Holmberg, Erik C; Robinson, David E; Garmo, Hans G; Stattin, Pär E

2013-01-01

Previous studies have shown a decreased risk of prostate cancer for childless men; however, the cause of the association remains to be elucidated. The aim of our study was to assess the risk of prostate cancer by fatherhood status, also considering potential confounding factors. In a case–control study in Prostate Cancer data Base Sweden 2.0, a nationwide, population-based cohort, data on number of children, marital status, education, comorbidity and tumor characteristics obtained through nationwide healthcare registers and demographic databases for 117,328 prostate cancer cases and 562,644 controls, matched on birth year and county of residence, were analyzed. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer overall and by risk category, adjusting for marital status and education. Childless men had a decreased risk of prostate cancer compared to fathers, OR = 0.83 (95% CI = 0.82–0.84), and risk was lower for low-risk prostate cancer, OR = 0.74 (95% CI = 0.72–0.77), than for metastatic prostate cancer, OR = 0.93 (95% CI = 0.90–0.97). Adjustment for marital status and education attenuated the association in the low-risk category, adjusted OR = 0.87 (95% CI = 0.84–0.91), whereas OR for metastatic cancer remained virtually unchanged, adjusted OR = 0.92 (95% CI = 0.88–0.96). Our data indicate that the association between fatherhood status and prostate cancer to a large part is due to socioeconomic factors influencing healthcare-seeking behavior including testing of prostate-specific antigen levels. PMID:23354735

Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans.

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Christopher A Haiman

2011-05-01

Full Text Available GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls, we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05 with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10(-4 that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17 over the alleles reported in the original GWAS (OR = 1.08. In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry.

Dosimetric Study of Pelvic Proton Radiotherapy for High-Risk Prostate Cancer

International Nuclear Information System (INIS)

Chera, Bhishamjit S.; Vargas, Carlos; Morris, Christopher G.; Louis, Debbie; Flampouri, Stella; Yeung, Daniel; Duvvuri, Srividya; Li Zuofeng; Mendenhall, Nancy Price

2009-01-01

Purpose: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). Methods and Materials: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. Results: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose 'bath' of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. Conclusions: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.

The Role of Dietary Fat throughout the Prostate Cancer Trajectory

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Katie M. Di Sebastiano

2014-12-01

Full Text Available Prostate cancer is the second most common cancer diagnosed world-wide; however, patients demonstrate exceptionally high survival rates. Many lifestyle factors, including obesity and diet, are considered risk factors for advanced prostate cancer. Dietary fat is a fundamental contributor to obesity and may be specifically important for prostate cancer patients. Prostate cancer treatment can result in changes in body composition, affecting quality of life for survivors by increasing the risk of co-morbidities, like cardiovascular disease and diabetes. We aim to examine dietary fat throughout the prostate cancer treatment trajectory, including risk, cancer development and survivorship. Focusing on one specific nutrient throughout the prostate cancer trajectory provides a unique perspective of dietary fat in prostate cancer and the mechanisms that may exacerbate prostate cancer risk, progression and recurrence. Through this approach, we noted that high intake of dietary fat, especially, high intake of animal and saturated fats, may be associated with increased prostate cancer risk. In contrast, a low-fat diet, specifically low in saturated fat, may be beneficial for prostate cancer survivors by reducing tumor angiogenesis and cancer recurrence. The insulin-like growth factor (IGF/Akt signaling pathway appears to be the key pathway moderating dietary fat intake and prostate cancer development and progression.

Risk factors and characteristics of prostate cancer bone metastases

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Jun-ming LIN

2017-10-01

Full Text Available Objective To analyze the risk factors and characteristics of bone metastases in patients with prostate cancer. Methods Patients who were diagnosed as prostate cancer by biopsy and histopathologic analysis between June 2006 and June 2016 were included in this study. The clinical data of the patients were reviewed, and the demographic data, laboratory examination results and Gleason score were recorded. The correlations between clinical factors and bone metastasis were analyzed, and the risk factors of bone metastasis were identified. Results A total of 585 patients were recruited in this study, including 228 with bone metastasis and 357 without bone metastasis. Of the patients with bone metastasis, the incidence of pelvic metastasis was the highest, accounting for 81.58%, followed by spin (63.16% and rib (58.33%, and the incidence of clavicle metastasis was the lowest (14.47%. Logistic regression analysis showed that age 85.5U/L, prostate-specific antigen >79.88μg/L and Gleason score >7.5 were the risk factors of bone metastasis in prostate cancer. ROC curve analysis showed that the sensitivity of diagnosing bone metastasis was 56.1%, 66.7%, 68.4% and 56.1%, and the specificity was 56.6%, 81.8%, 70.0% and 65.3%, respectively for above 4 factors. Conclusions The most common site of bone metastasis in patients with prostate cancer is pelvis. Patients' age, concentrations of plasma ALP and PSA, and Gleason score are the risk factors for bone metastasis in patients with prostate cancer. DOI: 10.11855/j.issn.0577-7402.2017.08.09

Does Small Prostate Predict High Grade Prostate Cancer?

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Caliskan, S.; Kaba, S.; Koca, O.; Ozturk, M. I.

2017-01-01

Objective: The current study is aimed to assess the patients who underwent radical prostatectomy for prostate cancer and investigate the association between prostate size and adverse outcomes at final pathology. Study Design: Comparative, descriptive study. Place and Duration of Study: Haydarpasa Numune Training and Research Hospital, Turkey, from January 2008 to January 2016. Methodology: The patients treated with open radical prostatectomy for prostate cancer were reviewed. Patient characteristics including prostate specific antigen (PSA), free PSA levels, age, biopsy, and radical prostatectomy results were recorded. The patients whose data were complete or prostate weight was equal to or less than 80 gm, were included in the study. Patients with < 40 gm prostate weight was in group 1 and the patients in group 2 had a prostate weight from 40 to 80 gm. High grade prostate cancer was defined to have a Gleason score between 7 or higher at biopsy and final pathology. Pathology and biopsy results were compared within groups. MedCalc Statistical Software demo version was used for statistical analyses. Results: There were 162 patients in this study. Of these, 71 (43.82 percent) patients were in group 1 and 91 (56.17 percent) patients were in group 2. The age ranged from 49 to 76 years. Mean value of 62.70 +-6.82 and 65.82 +- 5.66 years in group 1 and 2, respectively. Fifty (70.42 percent) and 68 patients (74.74 percent) had a Gleason score of 6 in group 1 and 2, respectively. Organconfined disease was reported in 53 patients (74.64 percent) in group 1 and in 78 patients (85.71 percent) in group 2. Gleason score concordance between biopsy and prostatectomy was reported in 61 patients (67.03 percent) and downgrading was detected in 4 patients (4.4 percent) in group 2. The median tumor volume of the patients was 4.47 cm/sup 3/ in group 1 and 6 cm/sup 3/ in group 2 (p=0.502). High grade prostate cancer was reported in 52.11 percent and 45.05 percent of the patients in

Male pattern baldness and the risk of prostate cancer.

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Yassa, M; Saliou, M; De Rycke, Y; Hemery, C; Henni, M; Bachaud, J M; Thiounn, N; Cosset, J M; Giraud, P

2011-08-01

Androgens play a role in the development of both androgenic alopecia, commonly known as male pattern baldness, and prostate cancer. We set out to study if early-onset androgenic alopecia was associated with an increased risk of prostate cancer later in life. A total of 669 subjects (388 with a history of prostate cancer and 281 without) were enrolled in this study. All subjects were asked to score their balding pattern at ages 20, 30 and 40. Statistical comparison was subsequently done between both groups of patients. Our study revealed that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01, P = 0.0285]. The pattern of hair loss was not a predictive factor for the development of cancer. There was no association between early-onset alopecia and an earlier diagnosis of prostate cancer or with the development of more aggressive tumors. This study shows an association between early-onset androgenic alopecia and the development of prostate cancer. Whether this population can benefit from routine prostate cancer screening or systematic use of 5-alpha reductase inhibitors as primary prevention remains to be determined.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

International Nuclear Information System (INIS)

Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

2013-01-01

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10

Risk of prostate cancer among cancer survivors in the Netherlands

NARCIS (Netherlands)

Kok, D.E.G.; Schans, van de S.A.; Liu, L.; Kampman, E.; Coebergh, J.W.; Kiemeney, L.A.; Soerjomataram, I.; Aben, K.K.

2013-01-01

In parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting. Methods Data from the

Sleep duration and disruption and prostate cancer risk: a 23-year prospective study

Science.gov (United States)

Markt, Sarah C.; Flynn-Evans, Erin E.; Valdimarsdottir, Unnur A.; Sigurdardottir, Lara G.; Tamimi, Rulla M.; Batista, Julie L.; Haneuse, Sebastien; Lockley, Steven W.; Stampfer, Meir; Wilson, Kathryn M.; Czeisler, Charles A.; Rider, Jennifer R.; Mucci, Lorelei A.

2015-01-01

Background Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer. Methods We prospectively followed 32,141 men in the Health Professionals Follow-Up Study (HPFS) who reported their typical sleep duration in 1987, 2000 and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004-2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer. Results In 1987, 2% of men reported sleeping ≤5 hours/night. We found no association between habitual sleep duration or change in sleep duration with risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared to those who reported always feeling rested when they woke up (RR=3.05, 95% CI=1.15-8.10). Conclusions We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes. Impact We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men. PMID:26677208

Age-dependent associations between androgenetic alopecia and prostate cancer risk.

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Muller, David C; Giles, Graham G; Sinclair, Rod; Hopper, John L; English, Dallas R; Severi, Gianluca

2013-02-01

Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.

Can the prostate brachytherapy by permanent implants represent an alternative to external radiotherapy for the localised prostate cancers with intermediary risk?

International Nuclear Information System (INIS)

Farnault, B.; Duberge, T.; Salem, N.; Boher, J.M.; Gravis, G.; Bladou, F.; Jochen, W.; Resbeut, M.

2009-01-01

Purpose: the prostate brachytherapy stands out as treatment of low risk prostate cancers, but the data concerning its use as exclusive treatment of intermediary risk prostate cancer are rare. We present a retrospective analysis of intermediary risk prostate cancers which treatment was either an external conformal radiotherapy or an exclusive brachytherapy. conclusion: In this mono centric series, the brachytherapy brings excellent results in comparison with external conformal radiotherapy with dose escalation and could be proposed as alternative to patients suffering of intermediary risk prostate cancer. (N.C.)

The influence of family history on cognitive heuristics, risk perceptions, and prostate cancer screening behavior.

Science.gov (United States)

McDowell, Michelle E; Occhipinti, Stefano; Chambers, Suzanne K

2013-11-01

To examine how family history of prostate cancer, risk perceptions, and heuristic decision strategies influence prostate cancer screening behavior. Men with a first-degree family history of prostate cancer (FDRs; n = 207) and men without a family history (PM; n = 239) completed a Computer Assisted Telephone Interview (CATI) examining prostate cancer risk perceptions, PSA testing behaviors, perceptions of similarity to the typical man who gets prostate cancer (representativeness heuristic), and availability of information about prostate cancer (availability heuristic). A path model explored family history as influencing the availability of information about prostate cancer (number of acquaintances with prostate cancer and number of recent discussions about prostate cancer) to mediate judgments of risk and to predict PSA testing behaviors and family history as a moderator of the relationship between representativeness (perceived similarity) and risk perceptions. FDRs reported greater risk perceptions and a greater number of PSA tests than did PM. Risk perceptions predicted increased PSA testing only in path models and was significant only for PM in multi-Group SEM analyses. Family history moderated the relationship between similarity perceptions and risk perceptions such that the relationship between these variables was significant only for FDRs. Recent discussions about prostate cancer mediated the relationships between family history and risk perceptions, and the number of acquaintances men knew with prostate cancer mediated the relationship between family history and PSA testing behavior. Family history interacts with the individuals' broader social environment to influence risk perceptions and screening behavior. Research into how risk perceptions develop and what primes behavior change is crucial to underpin psychological or public health intervention that seeks to influence health decision making.

High body mass index and cancer risk

DEFF Research Database (Denmark)

Benn, Marianne; Tybjærg-Hansen, Anne; Smith, George Davey

2016-01-01

of follow-up (range 0-37), 8002 developed non-skin cancer, 3347 non-melanoma skin cancer, 1396 lung cancer, 637 other smoking related cancers, 1203 colon cancer, 159 kidney cancer, 1402 breast cancer, 1062 prostate cancer, and 2804 other cancers. Participants were genotyped for five genetic variants...... with a BMI ≥ 30 versus 18.5-24.9 kg/m(2). Corresponding risk of breast cancer was 20 % (0-44 %) higher in postmenopausal women. BMI was not associated with risk of colon, kidney, other smoking related cancers, prostate cancer, or other cancers. In genetic analyses, carrying 7-10 versus 0-4 BMI increasing......High body mass index (BMI) has been associated with increased risk of some cancer. Whether these reflect causal associations is unknown. We examined this issue. Using a Mendelian randomisation approach, we studied 108,812 individuals from the general population. During a median of 4.7 years...

Replication of prostate cancer risk loci in a Japanese case-control association study.

Science.gov (United States)

Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L

2009-10-07

Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

Role of hormonal therapy in the management of intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation

International Nuclear Information System (INIS)

Lee, Lucille N.; Stock, Richard G.; Stone, Nelson N.

2002-01-01

Purpose: To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation. Methods and Materials: Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score ≥7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses. Results: HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA ≤15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%. Conclusion: In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses

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

The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

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Cristiano Capurso

2017-08-01

Full Text Available Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil

Sociodemographic status, stress, and risk of prostate cancer. A prospective cohort study

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Nielsen, Naja Rod; Kristensen, Tage S; Zhang, Zuo-Feng

2007-01-01

PURPOSE: The social gradient in prostate cancer incidence observed in several studies may be a result of differential access to prostate cancer screening. We aim to assess if socioeconomic status, stress, and marital status are associated with prostate cancer risk in a population with free access...... to health care. METHODS: The 5,496 men who participated in the Copenhagen City Heart Study were asked about their income, educational level, stress level, and marital status during 1981-1983. These men were prospectively followed up in the Danish Cancer Registry until the end of 2002 and fewer than 0...... in prostate cancer risk according to stress (HR = 0.99; 95% CI: 0.90-1.09) or marital status. CONCLUSION: In a racially homogeneous population of Caucasians with free access to health care, we found no evidence of a relation between sociodemographic variables or stress and subsequent risk of prostate cancer....

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 ...

Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

DEFF Research Database (Denmark)

Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

2016-01-01

PURPOSE: Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case-control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. METHODS: We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000-2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75-150 mg) or nonaspirin NSAID use, adjusted for potential confounders. RESULTS: Use of low-dose aspirin...

Efficacy of modest dose irradiation in combination with long-term endocrinal treatment for high-risk prostate cancer. A preliminary report

International Nuclear Information System (INIS)

Sasaki, Tomonari; Nakamura, Katsumasa; Shioyama, Yoshiyuki

2004-01-01

Although radiotherapy in combination with endocrinal manipulation has been identified as an effective treatment for patients with high-risk prostate cancer, the optimal dose for locoregional control of prostate cancer in combination with hormonal therapy has not yet been determined. The efficacy of modest doses of irradiation (60-62 Gy) combined with long-term endocrinal treatment for patients with high-risk prostate cancer (defined as a pretreatment prostate-specific antigen (PSA) level greater than 20 ng/ml or a Gleason's score of 8-10 or T3-T4 disease) was analyzed in 60 Japanese patients. The patients included in this study had received radical radiotherapy with long-term endocrinal manipulation in the period between 1993 and 2000. The median age of the patients was 70 years (range, 56-83). Neoadjuvant hormonal therapy with a median duration of 3.9 months was performed prior to radiotherapy, and hormonal therapy was continued until recurrence. A median dose of 61.4 Gy (range, 44-71.4) was delivered to the prostate. Pelvic node irradiation was performed in 49 patients (81.6%). After a median follow-up period of 28.5 months, the overall survival, cause-specific survival and biochemical relapse-free survival at 3 years were 94.4%, 96% and 89.8%, respectively. Local failure was observed in one patient, distant metastases were observed in three patients and a late toxic effect greater than Grade 2 was not observed in any patients. This study, though preliminary due to a short-term follow-up period, reveals the possibility that modest doses of irradiation combined with long-term endocrinal treatment could be an effective means of achieving excellent local control of high-risk prostate cancer. (author)

A Framework for the Identification of Men at Increased Risk for Prostate Cancer

NARCIS (Netherlands)

Roobol, Monique J.; Schroder, Fritz H.; Crawford, E. David; Freedland, Stephen J.; Sartor, A. Oliver; Fleshner, Neil; Andriole, Gerald L.

2009-01-01

Purpose: We assessed the risk of prostate cancer over time, and the implications for screening strategies and potential risk reduction approaches to provide a framework for clinical use of this approach concordant with the use of prostate specific antigen as a marker of current prostate cancer risk.

A Framework for the Identification of Men at Increased Risk for Prostate Cancer

NARCIS (Netherlands)

Roobol, Monique J.; Schroder, Fritz H.; Crawford, E. David; Freedland, Stephen J.; Sartor, A. Oliver; Fleshner, Neil; Andriole, Gerald L.

Purpose: We assessed the risk of prostate cancer over time, and the implications for screening strategies and potential risk reduction approaches to provide a framework for clinical use of this approach concordant with the use of prostate specific antigen as a marker of current prostate cancer risk.

Can the Mediterranean diet prevent prostate cancer?

Science.gov (United States)

Itsiopoulos, Catherine; Hodge, Allison; Kaimakamis, Mary

2009-02-01

Prostate cancer is the second most common cancer in men worldwide. Despite the global importance of this cancer, until recently little was known about risk factors apart from the well-established factors: age, family history and country of birth. The large worldwide variation in prostate cancer risk and increased risk in migrants moving from low to high risk countries provides strong support for modifiable environmental factors. We have based our review on the findings of a systematic review undertaken by an expert panel on behalf of the World Cancer Research Fund and the American Institute for Cancer Research, and new data since then, linking identified foods and nutrients with prostate cancer. Evidence indicates that foods containing lycopene, as well as selenium and foods containing it, probably protect against prostate cancer, and excess consumption of foods or supplements containing calcium are a probable cause of this cancer. The expert panel also concluded that it is unlikely that beta-carotene (whether from foods or supplements) has a substantial effect on the risk of this cancer. A recent review on environmental factors in human prostate cancer also found that there were protective effects of vitamin E, pulses, soy foods and high plasma 1,25-dihydroxyvitamin D levels. The Mediterranean diet is abundant in foods that may protect against prostate cancer and is associated with longevity and reduced cardiovascular and cancer mortality. Compared with many Western countries Greece has lower prostate cancer mortality and Greek migrant men in Australia have retained their low risk for prostate cancer. Consumption of a traditional Mediterranean diet, rich in bioactive nutrients, may confer protection to Greek migrant men, and this dietary pattern offers a palatable alternative for prevention of this disease.

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Science.gov (United States)

Albanes, Demetrius; Till, Cathee; Klein, Eric A; Goodman, Phyllis J; Mondul, Alison M; Weinstein, Stephanie J; Taylor, Philip R; Parnes, Howard L; Gaziano, J Michael; Song, Xiaoling; Fleshner, Neil E; Brown, Powel H; Meyskens, Frank L; Thompson, Ian M

2014-09-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine. ©2014 American Association for Cancer Research.

Prostate cancer may trigger paraneoplastic limbic encephalitis

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Jakobsen, Jakob Kristian; Zakharia, Elias Raja; Boysen, Anders Kindberg Fossø

2013-01-01

-Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis...

Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and type 2 diabetes mellitus.

Science.gov (United States)

Häggström, Christel; Van Hemelrijck, Mieke; Garmo, Hans; Robinson, David; Stattin, Pär; Rowley, Mark; Coolen, Anthony C C; Holmberg, Lars

2018-05-09

Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of this study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6 years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment. This article is protected by copyright. All rights reserved. © 2018 UICC.

Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.

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Ross, Ashley E; Hughes, Robert M; Glavaris, Stephanie; Ghabili, Kamyar; He, Ping; Anders, Nicole M; Harb, Rana; Tosoian, Jeffrey J; Marchionni, Luigi; Schaeffer, Edward M; Partin, Alan W; Allaf, Mohamad E; Bivalacqua, Trinity J; Chapman, Carolyn; O'Neal, Tanya; DeMarzo, Angelo M; Hurley, Paula J; Rudek, Michelle A; Antonarakis, Emmanuel S

2017-11-28

To determine the pharmacodynamic effects of Sonidegib (LDE-225) in prostate tumor tissue from men with high-risk localized prostate cancer, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy. We conducted a prospective randomized (Sonidegib vs. observation) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy. The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue. Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy, and safety. Fourteen men were equally randomized (7 per arm) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy. Six of seven men (86%) in the Sonidegib arm (and none in the control group) achieved a GLI1 suppression of at least two-fold. In the Sonidegib arm, drug was detectable in plasma and in prostatic tissue; and median intra-patient GLI1 expression decreased by 63-fold, indicating potent suppression of Hedgehog signaling. Sonidegib was well tolerated, without any Grade 3-4 adverse events observed. Disease-free survival was comparable among the two arms (HR = 1.50, 95% CI 0.26-8.69, P = 0.65). Hedgehog pathway activity (as measured by GLI1 expression) was detectable at baseline in men with localized high-risk prostate cancer. Sonidegib penetrated into prostatic tissue and induced a >60-fold suppression of the Hedgehog pathway. The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear.

Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

International Nuclear Information System (INIS)

Nanda, Akash; Chen, M.-H.; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

2010-01-01

Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

Entacapone and prostate cancer risk in patients with Parkinson's disease.

Science.gov (United States)

Korhonen, Pasi; Kuoppamäki, Mikko; Prami, Tuire; Hoti, Fabian; Christopher, Solomon; Ellmén, Juha; Aho, Valtteri; Vahteristo, Mikko; Pukkala, Eero; Haukka, Jari

2015-04-15

The association between Parkinson's disease (PD) and prostate cancer, both common in elderly men, is disputable. In the STRIDE-PD study, prostate cancer developed in 9 patients (3.7%) receiving levodopa/carbidopa with entacapone, a catechol-O-methyltransferase inhibitor, versus 2 cases (0.9%) without entacapone. The current pharmacoepidemiological study aimed to determine whether entacapone increases prostate cancer incidence or mortality in PD patients and whether cumulative exposure affects these rates. We performed a retrospective cohort study using population-wide health care registers with patient-level linkage. Prostate cancer incidence and mortality were modeled by Cox's proportional hazards models. Use of entacapone with l-dopa/dopa decarboxylase inhibitor caused no increased risk of prostate cancer incidence (hazard ratio [HR]: 1.05; 95% confidence interval: 0.76-1.44) or mortality (0.93; 0.43-1.98). The HR for cumulative entacapone use of >360 days versus never-use was 0.82 (0.56-1.18) for prostate cancer incidence and 1.27 (0.60-2.72) for prostate cancer mortality. © 2015 International Parkinson and Movement Disorder Society.

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer

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Antonio B. Porcaro

2014-09-01

Full Text Available Background: Chronic inflammatory infiltrate (CII might be involved in prostate cancer (PCA and benign hyperplasia (BPH; however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. Objective: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. Design, setting, and participants: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years and PSA (ug/l; moreover, CII+, glandular atrophy (GA+, glandular hyperplasia (GH+, prostate Intraepithelial neoplasm (PIN+, atypical small acinar cell proliferation (ASAP+ and PCA positive cores (P+ were evaluated as categorical and continuous (proportion of positive cores. Outcome measurements and statistical analysis: Associations of CII+ and PCA risk were assessed by statistical methods. Results and limitations: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8 resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26 and HGPCA (P = 0.0005; OR = 0.05. Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. Conclusions: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in

Androgenic alopecia is not useful as an indicator of men at high risk of prostate cancer.

NARCIS (Netherlands)

Cremers, R.G.H.M.; Aben, K.K.H.; Vermeulen, S.; Heijer, M. den; Oort, I.M. van; Kiemeney, L.A.L.M.

2010-01-01

BACKGROUND: Androgens are assumed to play a central role in the pathophysiology of both prostate cancer (PC) and androgenic alopecia (AA). A correlation between the two phenotypes may be relevant for identification of men at high risk of PC. We evaluated the association between AA at different ages

Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

Science.gov (United States)

Beebe-Dimmer, Jennifer L; Yee, Cecilia; Paskett, Electra; Schwartz, Ann G; Lane, Dorothy; Palmer, Nynikka R A; Bock, Cathryn H; Nassir, Rami; Simon, Michael S

2017-12-13

Evidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated. Analyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White). Of 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54). Our findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers.

Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Keshaviah, Aparna; Manola, Judith; Cote, Kerri; Loffredo, Marian; Iskrzytzky, Olga; Renshaw, Andrew A.

2002-01-01

Purpose: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. Methods and Materials: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. Results: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of ≤50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p=0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p 50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings

Ultraviolet radiation: effects on risks of prostate cancer and other internal cancers

International Nuclear Information System (INIS)

Moon, Samuel J.; Fryer, Anthony A.; Strange, Richard C.

2005-01-01

Governmental and research agencies worldwide have strongly advocated sun avoidance strategies in an attempt to counter marked increases in skin cancer incidence. Concurrently, there are reports describing widespread Vitamin D 3 deficiency. Because 1,25-dihydroxyvitamin D 3 , through interaction with the Vitamin D receptor, exerts pleiotrophic effects, such deficiency might be expected to have clinical consequences. Indeed, various reports indicate that exposure to ultraviolet radiation (UVR) exerts a protective effect on development of some common diseases including internal cancers and multiple sclerosis. We describe studies indicating that modest exposure reduces risk of prostate cancer. The effect of UVR is mediated by skin type; at lower levels of exposure a relative inability to effect skin pigmentation is protective presumably because it allows more efficient Vitamin D 3 synthesis. Polymorphic variants in genes associated with pigmentation including melanocyte stimulating hormone receptor and tyrosinase are also associated with prostate cancer risk. Overall, though preliminary and requiring cautious interpretation, these data indicate that moderate UVR exposure together with characteristics linked with less effective tanning confer reduced prostate cancer risk. Clearly, it is important to define safe levels of UVR that do not result in increased risk of skin cancers such as malignant melanoma

Ultraviolet radiation: effects on risks of prostate cancer and other internal cancers

Energy Technology Data Exchange (ETDEWEB)

Moon, Samuel J. [Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, Hartshill Campus, Stoke-on-Trent, ST4 7PA Staffordshire (United Kingdom); Fryer, Anthony A. [Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, Hartshill Campus, Stoke-on-Trent, ST4 7PA Staffordshire (United Kingdom); Strange, Richard C. [Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, Hartshill Campus, Stoke-on-Trent, ST4 7PA Staffordshire (United Kingdom)]. E-mail: paa00@keele.ac.uk

2005-04-01

Governmental and research agencies worldwide have strongly advocated sun avoidance strategies in an attempt to counter marked increases in skin cancer incidence. Concurrently, there are reports describing widespread Vitamin D{sub 3} deficiency. Because 1,25-dihydroxyvitamin D{sub 3}, through interaction with the Vitamin D receptor, exerts pleiotrophic effects, such deficiency might be expected to have clinical consequences. Indeed, various reports indicate that exposure to ultraviolet radiation (UVR) exerts a protective effect on development of some common diseases including internal cancers and multiple sclerosis. We describe studies indicating that modest exposure reduces risk of prostate cancer. The effect of UVR is mediated by skin type; at lower levels of exposure a relative inability to effect skin pigmentation is protective presumably because it allows more efficient Vitamin D{sub 3} synthesis. Polymorphic variants in genes associated with pigmentation including melanocyte stimulating hormone receptor and tyrosinase are also associated with prostate cancer risk. Overall, though preliminary and requiring cautious interpretation, these data indicate that moderate UVR exposure together with characteristics linked with less effective tanning confer reduced prostate cancer risk. Clearly, it is important to define safe levels of UVR that do not result in increased risk of skin cancers such as malignant melanoma.

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,

Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer: Report From the 2015 Coffey-Holden Prostate Cancer Academy Meeting

Science.gov (United States)

Miyahira, Andrea K.; Lang, Joshua M.; Den, Robert B.; Garraway, Isla P.; Lotan, Tamara L.; Ross, Ashley E.; Stoyanova, Tanya; Cho, Steve Y.; Simons, Jonathan W.; Pienta, Kenneth J.; Soule, Howard R.

2018-01-01

BACKGROUND The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: “Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer,” was held in La Jolla, California from June 25 to 28, 2015. METHODS The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. RESULTS The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. DISCUSSION This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. PMID:26477609

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

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King Christopher R

2011-01-01

Full Text Available Abstract Purpose Hypofractionated, stereotactic body radiotherapy (SBRT is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Method and Materials Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method and RTOG toxicity outcomes were assessed. Results At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%. Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusion Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.

CHEK2∗1100delC Mutation and Risk of Prostate Cancer

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Victoria Hale

2014-01-01

Full Text Available Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18 for unselected cases and 3.39 (1.78–6.47 for familial cases, indicating that CHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

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Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

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2017-10-01

AWARD NUMBER: W81XWH-15-1-0529 TITLE: A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk PRINCIPAL INVESTIGATOR...AND SUBTITLE A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer is the most commonly diagnosed cancer in

Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies.

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Hwang, Ye Won; Kim, Soo Young; Jee, Sun Ha; Kim, Youn Nam; Nam, Chung Mo

2009-01-01

Soybean products have been suggested to have a chemo preventive effect against prostate cancer. The aim of this study was to provide a comprehensive meta-analysis on the extent of the possible association between soy-based food consumption and the risk of prostate cancer. Five cohort studies and 8 case-control studies were identified using MEDLINE, EMBASE, CINAHL, Korea Medical Database, KoreaMed, Korean studies Information Service System, Japana Centra Revuo Medicina, China National Knowledge Infrastructure, and a manual search. Summary odds ratios (ORs) comparing high versus low categories of soybean consumptions were calculated on the basis of the random effect model. We analyzed the associations based on the different types of soybean consumptions. The summary ORs (95% CI) for total soy foods were 0.69 (CI = 0.57-0.84) and 0.75 (CI = 0.62-0.89) for nonfermented soy foods. Among individual soy foods, only tofu yielded a significant value of 0.73 (CI = 0.57-0.92). Consumption of soybean milk, miso, or natto did not significantly reduce the risk of prostate cancer. Genistein and daidzein were associated with a lower risk of prostate cancer. This systematic review suggests that soy food consumption could lower the risk of prostate cancer. This conclusion, however, should be interpreted with caution because various biases can affect the results of a meta-analysis.

Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse.

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Laing, Robert; Uribe, Jennifer; Uribe-Lewis, Santiago; Money-Kyrle, Julian; Perna, Carla; Chintzoglou, Stylianos; Khaksar, Sara; Langley, Stephen E M

2018-04-01

To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised prostate cancer. Analysis of clinical outcomes from a prospective cohort of patients treated with LDR-PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse-free survival (RFS), overall survival (OS), prostate cancer-specific survival (PCSS), and metastases-free survival (MFS), were analysed together with patient-reported symptom scores and physician-reported adverse events. The NICE and NCCN criteria identified 267 and 202 high-risk patients, respectively. NICE-defined patients had significantly lower pre-treatment PSA levels, Gleason scores LDR-PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log-rank P = 0.637), and OS 93% and 94%, respectively (log-rank P = 0.481). All of the survival estimates were similar between LDR-PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment-related toxicity was also similar between the treatment methods. LDR-PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR-PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high-risk factors. © 2018 The Authors BJU International © 2018 BJU International

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

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Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.; Reddy, Chandana A.; Thousand, Richard A.; Vassil, Andrew; Stovsky, Mark; Berglund, Ryan K.; Klein, Eric A.; Stephans, Kevin L.

2016-01-01

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

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Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.; Reddy, Chandana A.; Thousand, Richard A.; Vassil, Andrew [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stovsky, Mark; Berglund, Ryan K.; Klein, Eric A. [Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephans, Kevin L., E-mail: stephak@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

2016-07-01

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

Sedentary behavior and prostate cancer risk in the NIH-AARP Diet and Health Study.

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Lynch, Brigid M; Friedenreich, Christine M; Kopciuk, Karen A; Hollenbeck, Albert R; Moore, Steven C; Matthews, Charles E

2014-05-01

Sedentary behavior (sitting time) has been proposed as an independent risk factor for some cancers; however, its role in the development of prostate cancer has not been determined. We examined the prospective associations of self-reported daily sitting time and daily television/video viewing time with the risk of developing or dying from prostate cancer among 170,481 men in the NIH-AARP Diet and Health Study. We estimated HRs and 95% confidence intervals (CI) using Cox proportional hazards regression. Between 1996 and 2006, there were 13,751 incident (including 1,365 advanced) prostate cancer cases identified; prostate cancer mortality (through 2008) was 669. No strong or significant association with prostate cancer risk was seen in fully adjusted models for either daily sitting or television/video time. There were some suggestions of effect modification by body mass index (BMI; interaction for television/video time and BMI, P = 0.02). For total prostate cancer risk, television/video time was associated with a slightly elevated, but nonsignificant, increase amongst obese men (HR = 1.28; 95% CI, 0.98-1.69); a null association was observed amongst overweight men (HR = 1.04; 0.89-1.22); and, for men with a normal BMI, television/video time was associated with a nonsignificant risk decrease (HR = 0.82; 95% CI, 0.66-1.01). Similar patterns were observed for total daily sitting and television/video time in advanced prostate cancer and prostate cancer mortality. Sedentary behavior seems to play a limited role in the development of prostate cancer; however, we cannot rule out potential effect modification by BMI or the impact of measurement error on results. ©2014 AACR.

Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality

DEFF Research Database (Denmark)

Ørsted, David Dynnes; Bojesen, Stig E; Kamstrup, Pia R

2013-01-01

BACKGROUND: It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population. OBJECTIVE: To determine whether long-term PSAV improves classification of PCa risk...

Case-control study of toenail cadmium and prostate cancer risk in Italy

International Nuclear Information System (INIS)

Vinceti, Marco; Venturelli, Marianna; Sighinolfi, Chiara; Trerotoli, Paolo; Bonvicini, Francesca; Ferrari, Angela; Bianchi, Giampaolo; Serio, Gabriella; Bergomi, Margherita; Vivoli, Gianfranco

2007-01-01

A role of cadmium exposure in prostate cancer etiology has been suggested by epidemiologic and laboratory studies, but conclusive evidence on this topic is still lacking. We investigated the relation between cadmium exposure, estimated by determining toenails cadmium levels, and prostate cancer risk in forty patients newly diagnosed with prostate cancer and fifty-eight hospital controls recruited in two provinces from southern and northern Italy. We found an excess cancer risk in subjects in the third and fourth (highest) quartiles of toenail cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with subjects in the bottom quartile. Results were basically unchanged when limiting the analysis to each province or entering toenail cadmium concentrations as continuous values in the regression model (P = 0.004). Despite the limited statistical stability of the point estimates, these findings appear to support the hypothesis that cadmium exposure increases prostate cancer risk

Prostate Cancer

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... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

Active surveillance can reduce overtreatment in patients with low-risk prostate cancer

DEFF Research Database (Denmark)

Thomsen, Frederik Birkebæk; Røder, Martin Andreas; Hvarness, Helle

2013-01-01

The incidence of prostate cancer in Denmark rose approximately 50% from 2000 to 2009 in parallel with the introduction of prostate-specific antigen (PSA)-testing. Available evidence indicates a significant overtreatment of patients with low-risk prostate cancer. Active surveillance has been...

Prediction of individual genetic risk to prostate cancer using a polygenic score

DEFF Research Database (Denmark)

Szulkin, Robert; Whitington, Thomas; Eklund, Martin

2015-01-01

BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate ca...

Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

International Nuclear Information System (INIS)

Zeliadt, Steven B.; Potosky, Arnold L.; Penson, David F.; Etzioni, Ruth

2006-01-01

Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease

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...

PET/CT in staging of the high risk prostate cancer

International Nuclear Information System (INIS)

Bergero, M.A.; David, C.; Dipatto, F.; Popeneciu, V.; Ríos, L.; Faccio, F.

2016-01-01

Objectives: In the last decade multimodal management of the high risk prostate cancer (HRPC) is a therapeutic option in selected patients and the staging of these patients depends on the current diagnostic methods (DM) which have low diagnostic accuracy for detecting metastasis (MTS). The positron emission tomography/computed tomography (PET/CT) would have a greater diagnostic accuracy and it is presented as a better DM for staging prostate cancer (PC). The aim of this article is present 2 patients in whom PET/CT modified the therapeutic decision and conduct a literature review. Materials and methods: 2 patients with HRPC who performed PET/CT and it modified the therapeutic behavior were described and a systematic review of the literature was conducted using PubMed, Embase, SciELO and Cochrane answering the question: has PET/CT a place in HRPC staging? Results: TPET/CT has a sensitivity and specificity between 19% to 100% and 67% to 98,5 %, respectively, in assessing nodal involvement by PC and between 84% to 96% and 92.3% to 100%, respectively, in assessing bone involvement by PC. Besides PET/CT allowed to modify the therapeutic behavior between 20% to 40% of the patients with PC. Conclusions: PET/CT has good specificity and moderate sensitivity for detecting lymph node MTS and good sensitivity and specificity for detecting bone MTS. Besides PET/CT modified the therapeutic behavior in 1/3 of cases and it allowed us to modify the therapeutic behavior in our series. (authors) [es

Risk factors for prostate cancer: An hospital-based case-control study from Mumbai, India

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B Ganesh

2011-01-01

Full Text Available Background : In India, prostate cancer is one of the five leading sites of cancers among males in all the registries. Very little is known about risk factors for prostate cancer among the Indian population. Objectives : The present study aims to study the association of lifestyle factors like chewing (betel leaf with or without tobacco, pan masala, gutka, smoking (bidi, cigarette, comorbid conditions, diet, body mass index (BMI, family history, vasectomy with prostate cancer. Materials and Methods : This an unmatched hospital-based case-control study, comprised of 123 histologically proven prostate ′cancer cases′ and 167 ′normal controls. Univariate and regression analysis were applied for obtaining the odds ratio for risk factors. Results : The study revealed that there was no significant excess risk for chewers, alcohol drinkers, tea and coffee drinkers, family history of cancer, diabetes, vasectomy and dietary factors. However, patients with BMI >25 (OR = 2.1, those with hypertension history (OR = 2.5 and age >55 years (OR = 19.3 had enhanced risk for prostate cancer. Conclusions : In the present study age, BMI and hypertension emerged as risk factors for prostate cancer. The findings of this study could be useful to conduct larger studies in a more detailed manner which in turn can be useful for public interest domain.

Relationship between male pattern baldness and the risk of aggressive prostate cancer: an analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Science.gov (United States)

Zhou, Cindy Ke; Pfeiffer, Ruth M; Cleary, Sean D; Hoffman, Heather J; Levine, Paul H; Chu, Lisa W; Hsing, Ann W; Cook, Michael B

2015-02-10

Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort—the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric. During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score ≥ 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer. Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms. © 2014 by American Society of Clinical Oncology.

The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

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Hayley C Whitaker

2010-10-01

Full Text Available Microseminoprotein-beta (MSMB regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

Science.gov (United States)

Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

2010-10-13

Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

Pizza consumption and the risk of breast, ovarian and prostate cancer.

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Gallus, Silvano; Talamini, Renato; Bosetti, Cristina; Negri, Eva; Montella, Maurizio; Franceschi, Silvia; Giacosa, Attilio; La Vecchia, Carlo

2006-02-01

Pizza has been favourably related to the risk of prostate cancer in North America. Scanty information, however, is available on sex hormone-related cancer sites. We therefore studied the role of pizza consumption on the risk of breast, ovarian and prostate cancers using data from three hospital-based case-control studies conducted in Italy between 1991 and 2002. These included 2569 women with breast cancer, 1031 with ovarian cancer, 1294 men with prostate cancer, and a total of 4864 controls. Compared with non-pizza eaters, the multivariate odds ratios for eaters were 0.97 (95% confidence interval (CI) 0.86-1.10) for breast, 1.06 (95% CI 0.89-1.26) for ovarian and 1.04 (95% CI 0.88-1.23) for prostate cancer. Corresponding estimates for regular eaters (i.e. > or =1 portion per week) were 0.92 (95% CI 0.78-1.08), 1.00 (95% CI 0.80-1.25) and 1.12 (95% CI 0.88-1.43), respectively. Our results do not show a relevant role of pizza on the risk of sex hormone-related cancers. The difference with selected studies from North America suggests that dietary and lifestyle correlates of pizza eating vary between different populations and social groups.

Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: A 12 months analysis after three consecutive prostate biopsies

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Cosimo De Nunzio

2013-06-01

Full Text Available Purpose: To evaluate the risk of prostate cancer (PCa on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN. Materials and methods: From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE were scheduled for trans-rectal ultrasound (TRUS guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. Results: A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22% men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34% still showed HGPIN, 15 (35% were diagnosed with PCa and 9 (21% presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04. Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. Conclusions: Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.

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.

Plasma levels of nitrate and risk of prostate cancer: a prospective study.

Science.gov (United States)

Wu, Tianying; Wang, Yushan; Ho, Shuk-Mei; Giovannucci, Edward

2013-07-01

Nitrate and nitrite supplements have recently been shown to improve cardiovascular health, but there is concern that these supplements could contribute to the development of cancer. Previous small, cross-sectional studies reported positive associations between circulating nitrate/nitrite levels and cancer. Prospective studies examining the association between plasma nitrate and cancer, especially prostate cancer, are lacking. We conducted a nested case-control study within the Health Professionals Follow-up Study. Baseline blood samples were collected in 1994, and incident cases of prostate cancer were identified from 1997 to 2005. Baseline plasma levels of nitrate were measured in the 630 cases and 630 matched controls. We have found that baseline levels of plasma nitrate were not associated with risk of prostate cancer. Compared to quintile 1, the relative risk from quintiles 2 to 5 were 1.13 [95% confidence interval (CI), 0.78-1.63], 0.93 (95% CI, 0.63-1.38), 0.95 (95% CI, 0.65-1.39), and 0.99 (95% CI, 0.68-1.48); Ptrend was 0.9 after adjustment of multivariate risk factors. When analyses were restricted to men fasting more than 6 hours, the trend was similar. Furthermore, plasma nitrate seemed to be inversely associated with advanced-stage prostate cancer. The relative risk across extreme quartiles was 0.44 (95% CI, 0.17-1.12; Ptrend = 0.07) for the whole dataset and 0.30 (95% CI, 0.09-0.99; Ptrend = 0.05) for the fasting dataset. In summary, we did not find an increased risk of prostate cancer associated with higher plasma nitrate levels. A potential protective association between nitrate and aggressive forms of prostate cancer requires confirmation. Nitrate-nitrite-nitric oxide pathway has emerged as a new therapeutic pathway for chronic diseases. The results of this study certainly merit replications in other prospective studies.

Obesity, body composition, and prostate cancer

Directory of Open Access Journals (Sweden)

Fowke Jay H

2012-01-01

Full Text Available Abstract Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10 prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA to measure body composition and determine the association between prostate cancer and total body fat mass (FM fat-free mass (FFM, and percent body fat (%BF, and which body composition measure mediated the association between BMI or waist circumference (WC with prostate cancer. Methods The study used a multi-centered recruitment protocol targeting men scheduled for prostate biopsy. Men without prostate cancer at biopsy served as controls (n = 1057. Prostate cancer cases were classified as having Gleason 6 (n = 402, Gleason 7 (n = 272, or Gleason 8-10 (n = 135 cancer. BIA and body size measures were ascertained by trained staff prior to diagnosis, and clinical and comorbidity status were determined by chart review. Analyses utilized multivariable linear and logistic regression. Results Body size and composition measures were not significantly associated with low-grade (Gleason 6 prostate cancer. In contrast, BMI, WC, FM, and FFM were associated with an increased risk of Gleason 7 and Gleason 8-10 prostate cancer. Furthermore, BMI and WC were no longer associated with Gleason 8-10 (ORBMI = 1.039 (1.000, 1.081, ORWC = 1.016 (0.999, 1.033, continuous scales with control for total body FFM (ORBMI = 0.998 (0.946, 1.052, ORWC = 0.995 (0.974, 1.017. Furthermore, increasing FFM remained significantly associated with Gleason 7 (ORFFM = 1.030 (1.008, 1.052 and Gleason 8-10 (ORFFM = 1.044 (1.014, 1.074 after controlling for FM. Conclusions Our results

Advanced prostate cancer risk in relation to toenail selenium levels

NARCIS (Netherlands)

Geybels, M.S.; Verhage, B.A.J.; Schooten, F.J. van; Goldbohm, A.; Brandt, P.A. van den

2013-01-01

BACKGROUND: Selenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0737 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH...that there exist distinctive molecular correlates of PTEN loss in the context of ETS-negative versus ETS-positive human prostate cancers and that

CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer

DEFF Research Database (Denmark)

Hale, Victoria; Weischer, Maren; Park, Jong Y

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current...... knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 (∗)1100delC and its association with prostate cancer were identified....... Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases, indicating that CHEK2 (∗)1100delC mutation is associated with increased risk...

DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

International Nuclear Information System (INIS)

Jacobs, Corbin; Tumati, Vasu; Kapur, Payal; Yan, Jingsheng; Hong, David; Bhuiyan, Manzerul; Xie, Xian-Jin; Pistenmaa, David; Yu, Lan; Hsieh, Jer-Tsong; Saha, Debabrata; Kim, D. W. Nathan

2014-01-01

Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance–free survival (CRFS), and distant metastasis–free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage ≥T3a, or Gleason score ≥8, or prostate-specific antigen level ≥20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for

DOC-2/DAB2 Interacting Protein Status in High-Risk Prostate Cancer Correlates With Outcome for Patients Treated With Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Jacobs, Corbin; Tumati, Vasu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Kapur, Payal [Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Yan, Jingsheng [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hong, David; Bhuiyan, Manzerul [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Xie, Xian-Jin [Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Pistenmaa, David [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States); Yu, Lan [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong [Simmons Cancer Center, Dallas, Texas (United States); Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Saha, Debabrata [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States); Kim, D. W. Nathan, E-mail: Nathan.Kim@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Cancer Center, Dallas, Texas (United States)

2014-07-15

Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy. Methods and Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance–free survival (CRFS), and distant metastasis–free survival (DMFS). Log-rank test and Cox regression were used to determine significance of biomarker levels with clinical outcome. Results: Fifty-four patients with high-risk prostate cancer (stage ≥T3a, or Gleason score ≥8, or prostate-specific antigen level ≥20 ng/mL) treated with radiation therapy from 2005 to 2012 at our institution were evaluated. Nearly all patients expressed EZH2 (98%), whereas 28% of patients revealed DAB2IP reduction and 72% retained DAB2IP. Median follow-up was 34.0 months for DAB2IP-reduced patients, 29.9 months for DAB2IP-retained patients, and 32.6 months in the EZH2 study. Reduction in DAB2IP portended worse outcome compared with DAB2IP-retained patients, including FFBF (4-year: 37% vs 89%, P=.04), CRFS (4-year: 50% vs 90%, P=.02), and DMFS (4-year: 36% vs 97%, P=.05). Stratified EZH2 expression trended toward significance for worse FFBF and CRFS (P=.07). Patients with reduced DAB2IP or highest-intensity EZH2 expression exhibited worse FFBF (4-year: 32% vs 95%, P=.02), CRFS (4-year: 28% vs 100%, P<.01), and DMFS (4-year: 39% vs 100%, P=.04) compared with the control group. Conclusion: Loss of DAB2IP is a potent biomarker that portends worse outcome despite definitive radiation therapy for patients with high-risk prostate cancer. Enhancer of zeste homolog 2 is expressed in most high-risk tumors and is a less potent discriminator of outcome in this study. The DAB2IP status in combination with degree of EZH2 expression may be useful for

Shifting brachytherapy monotherapy case mix toward intermediate-risk prostate cancer.

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Muralidhar, Vinayak; Mahal, Brandon A; Ziehr, David R; Chen, Yu-Wei; Nezolosky, Michelle D; Viswanathan, Vidya B; Beard, Clair J; Devlin, Phillip M; Martin, Neil E; Orio, Peter F; Nguyen, Paul L

2015-01-01

The relative use of brachytherapy (BT) for prostate cancer has declined in recent years. In this setting, we sought to determine whether the case mix of BT monotherapy-treated men has changed over time in terms of risk group composition. The Surveillance, Epidemiology, and End Results database was used to identify 30,939 patients diagnosed with prostate adenocarcinoma between 2004 and 2011 who received BT monotherapy. The case mix of BT monotherapy patients was calculated by patient risk group and year of diagnosis. Between 2004 and 2011, the use of BT monotherapy declined overall. The relative percentage of men undergoing BT with low-risk disease declined by 4.5%, whereas the relative percentage of patients with intermediate-risk disease increased by 4.7%. Non-white patients and those from poorer counties did not show shifts in the risk group makeup of BT monotherapy patients, whereas white patients and those from wealthier counties did. Although fewer patients with prostate cancer are undergoing BT monotherapy, men with intermediate-risk disease comprised a significantly larger portion of the BT case mix in 2011 compared with 2004. Future research efforts by brachytherapists should be directed toward improving BT technique, optimizing radiation doses, and obtaining long-term followup data for patients with intermediate-risk prostate cancer. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

American Brachytherapy Society Task Group Report: Combination of brachytherapy and external beam radiation for high-risk prostate cancer.

Science.gov (United States)

Spratt, Daniel E; Soni, Payal D; McLaughlin, Patrick W; Merrick, Gregory S; Stock, Richard G; Blasko, John C; Zelefsky, Michael J

To review outcomes for high-risk prostate cancer treated with combined modality radiation therapy (CMRT) utilizing external beam radiation therapy (EBRT) with a brachytherapy boost. The available literature for high-risk prostate cancer treated with combined modality radiation therapy was reviewed and summarized. At this time, the literature suggests that the majority of high-risk cancers are curable with multimodal treatment. Several large retrospective studies and three prospective randomized trials comparing CMRT to dose-escalated EBRT have demonstrated superior biochemical control with CMRT. Longer followup of the randomized trials will be required to determine if this will translate to a benefit in metastasis-free survival, disease-specific survival, and overall survival. Although greater toxicity has been associated with CMRT compared to EBRT, recent studies suggest that technological advances that allow better definition and sparing of critical adjacent structures as well as increasing experience with brachytherapy have improved implant quality and the toxicity profile of brachytherapy. The role of androgen deprivation therapy is well established in the external beam literature for high-risk disease, but there is controversy regarding the applicability of these data in the setting of dose escalation. At this time, there is not sufficient evidence for the omission of androgen deprivation therapy with dose escalation in this population. Comparisons with surgery remain limited by differences in patient selection, but the evidence would suggest better disease control with CMRT compared to surgery alone. Due to a series of technological advances, modern combination series have demonstrated unparalleled rates of disease control in the high-risk population. Given the evidence from recent randomized trials, combination therapy may become the standard of care for high-risk cancers. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All

Common variants of xeroderma pigmentosum genes and prostate cancer risk.

Science.gov (United States)

Mirecka, Aneta; Paszkowska-Szczur, Katarzyna; Scott, Rodney J; Górski, Bohdan; van de Wetering, Thierry; Wokołorczyk, Dominika; Gromowski, Tomasz; Serrano-Fernandez, Pablo; Cybulski, Cezary; Kashyap, Aniruddh; Gupta, Satish; Gołąb, Adam; Słojewski, Marcin; Sikorski, Andrzej; Lubiński, Jan; Dębniak, Tadeusz

2014-08-10

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between several NER gene polymorphisms and PC risk, but most of them evaluated only single SNPs among XP genes and the results remain inconsistent. Out of 94 SNPs located in seven XP genes (XPA-XPG) a total of 15 SNPs were assayed in 720 unselected patients with PC and compared to 1121 healthy adults. An increased risk of disease was associated with the XPD SNP, rs1799793 (Asp312Asn) AG genotype (OR=2.60; p<0.001) and with the AA genotype (OR=531; p<0.0001) compared to the control population. Haplotype analysis of XPD revealed one protective haplotype and four associated with an increased disease risk, which showed that the A allele (XPD rs1799793) appeared to drive the main effect on promoting prostate cancer risk. Polymorphism in XPD gene appears to be associated with the risk of prostate cancer. Copyright © 2014. Published by Elsevier B.V.

ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Yu-Mei Wang

Full Text Available Many published data on the association between single nucleotide polymorphisms (SNPs in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE review and meta-analysis is to derive a more precise estimation of this relationship.A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to assess the strength of association.Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T and XbaI (A>G polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C, codon 325 (C>G, codon 594 (G>A and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed.Results from the current meta-analysis indicate that ESR1 PvuII (C>T polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G polymorphism may increase the risk of prostate cancer among American population.

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.

Blood lipids and prostate cancer

DEFF Research Database (Denmark)

Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

2016-01-01

Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...... into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL.......95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk...

Under-utilisation of high-dose-rate brachytherapy boost in men with intermediate-high risk prostate cancer treated with external beam radiotherapy.

Science.gov (United States)

Ong, Wee Loon; Evans, Sue M; Millar, Jeremy L

2018-04-01

The aim of this study was to evaluate the use of high-dose-rate brachytherapy (HDR-BT) boost with definitive external beam radiotherapy (EBRT) in prostate cancer (CaP) management. The study population comprised men with intermediate-high risk CaP captured in the population-based Prostate Cancer Outcome Registry Victoria (PCOR-Vic), treated with EBRT from January 2010 to December 2015. The primary outcome is the proportion of men who received HDR-BT boost. Multivariate logistic regressions were used to evaluate the effect of patient-, tumour- and treatment-factors on the likelihood of HDR-BT use. Medicare Benefit Schedule (MBS) data was accessed to evaluate the Australia-wide pattern of HDR-BT use. One thousand eight hundred and six patients were included in this study - 886 (49%) intermediate-risk, and 920 (51%) high-risk CaP patients. Overall, only 124 (7%) patients had EBRT + HDR-BT - 47 (5%) intermediate-risk and 77 (8%) high-risk CaP patients (P = 0.01). There is higher proportion of patients who had HDR-BT in public institutions (7% public vs. 3% private, P = 0.005) and in metropolitan centres (9% metropolitan vs. 2% regional, P Victorian men with CaP. The decline in HDR-BT use was also observed nationally. © 2017 The Royal Australian and New Zealand College of Radiologists.

Defining the implant treatment volume for patients with low risk prostate cancer: does the anterior base need to be treated?

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Davis, Ann; Vargas, Sara O.; Renshaw, Andrew A.; Jiroutek, Michael; Richie, Jerome P.

1999-01-01

Purpose: An increased incidence of acute urinary retention has been reported after interstitial prostate radiation therapy when the anterior base of the prostate gland receives 100% of the prescription dose. The frequency of prostate cancer in this location as a function of the pre-treatment prostate specific antigen (PSA), biopsy Gleason score, and 1992 American Joint Commission on Cancer Staging (AJCC) was determined. Methods and Materials: One hundred four men treated at the Brigham and Women's Hospital with radical prostatectomy for clinically localized prostate cancer between 1995-1996 comprised the study population. Prostatectomy specimens were whole mounted and the location of each tumor foci enumerated. Results: Of 269 foci of prostate cancer found in 39 low-risk prostate cancer patients (PSA 1c,2a ), a single focus (0.37%) was noted in the anterior base. Conversely, 20/355 (5.6%) and 18/251 (7.2%) tumor foci were noted in the anterior base in 43 patients with intermediate risk and 24 patients with high-risk disease, respectively. Conclusions: A new definition of the treatment volume excluding the anterior base for low-risk prostate cancer patients may be justified

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

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Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P; Southey, Melissa; John, Esther M; Conner, Thomas A; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Osorio, Ana; Weitzel, Jeffrey N; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-Ren; Walker, Lisa; Side, Lucy E; Porteous, Mary E; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B M; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A; Johannsson, Oskar Th; Barkardottir, Rosa B; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R; Pinto, Pedro; Spurdle, Amanda B; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y; Berger, Andreas; Singer, Christian F; Loud, Jennifer T; Greene, Mark H; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A; Caligo, Maria A; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M; Olopade, Olufunmilayo I; Nathanson, Katherine L; Domchek, Susan M; Lorenchick, Christa; Jankowitz, Rachel C; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Schmutzler, Rita K; Antoniou, Antonis C; Ottini, Laura

2017-07-10

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10 -6 ). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10 -9 ). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

An assessment of Prostate Cancer Research International: Active Surveillance (PRIAS) criteria for active surveillance of clinically low-risk prostate cancer patients

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da Silva, Vitor; Cagiannos, Ilias; Lavallée, Luke T.; Mallick, Ranjeeta; Witiuk, Kelsey; Cnossen, Sonya; Eastham, James A.; Fergusson, Dean A.; Morash, Chris; Breau, Rodney H.

2017-01-01

Introduction Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients. Methods A D’Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts. Results The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49–0.75), pT3 (OR 0.41; 95% CI 0.31–0.55), nodal metastases (OR 0.37; 95% CI 0.10–1.31), or any adverse feature (OR 0.56; 95% CI 0.45–0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46–1.09 and survival HR 0.72; 95% CI 0.36–1.47). Conclusions Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria. PMID:28798822

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

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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.

PSA testing for men at average risk of prostate cancer

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Bruce K Armstrong

2017-07-01

Full Text Available Prostate-specific antigen (PSA testing of men at normal risk of prostate cancer is one of the most contested issues in cancer screening. There is no formal screening program, but testing is common – arguably a practice that ran ahead of the evidence. Public and professional communication about PSA screening has been highly varied and potentially confusing for practitioners and patients alike. There has been much research and policy activity relating to PSA testing in recent years. Landmark randomised controlled trials have been reported; authorities – including the 2013 Prostate Cancer World Congress, the Prostate Cancer Foundation of Australia, Cancer Council Australia, and the National Health and Medical Research Council – have made or endorsed public statements and/or issued clinical practice guidelines; and the US Preventive Services Task Force is revising its recommendations. But disagreement continues. The contention is partly over what the new evidence means. It is also a result of different valuing and prioritisation of outcomes that are hard to compare: prostate cancer deaths prevented (a small and disputed number; prevention of metastatic disease (somewhat more common; and side-effects of treatment such as incontinence, impotence and bowel trouble (more common again. A sizeable proportion of men diagnosed through PSA testing (somewhere between 20% and 50% would never have had prostate cancer symptoms sufficient to prompt investigation; many of these men are older, with competing comorbidities. It is a complex picture. Below are four viewpoints from expert participants in the evolving debate, commissioned for this cancer screening themed issue of Public Health Research & Practice. We asked the authors to respond to the challenge of PSA testing of asymptomatic, normal-risk men. They raise important considerations: uncertainty, harms, the trustworthiness and interpretation of the evidence, cost (e.g. of using multiparametric

Red wine consumption and risk of prostate cancer: the California men's health study.

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Chao, Chun; Haque, Reina; Van Den Eeden, Stephen K; Caan, Bette J; Poon, Kwun-Yee T; Quinn, Virginia P

2010-01-01

Red wine contains polyphenol antioxidants that inhibit prostate cancer development in animal studies. We investigated the effect of red wine intake on the risk of prostate cancer using data prospectively collected in the California Men's Health Study (CMHS). CMHS is a multiethnic cohort of 84,170 men aged 45-69 years who were members of the Kaiser Permanente Southern and Northern California Health Plans. Information on demographic and lifestyle factors was collected using mailed questionnaires between 2002 and 2003. We used Cox models to estimate the effect of red wine on prostate cancer risk, adjusting for potential confounders. A total of 1,340 incident prostate cancer cases identified from Surveillance, Epidemiology and End Result-affiliated cancer registries were included in the analyses. We did not find a clear association between red wine intake and risk of prostate cancer. Hazard ratio (HR) estimates for consuming or =1 drink/week but or =1 drink/day were 0.89, 95% confidence interval (0.74-1.07), 0.99 (0.83-1.17) and 0.88 (0.70-1.12), respectively. Further, we observed no linear dose response. The lack of association for red wine intake was consistently observed when we restricted the analyses to those with and without a history of PSA screening. In addition, we also did not observe any association with prostate cancer for beer, white wine, liquor or combined alcoholic beverage intake (HR for combined alcoholic beverage intake of > or =5 drinks/day = 1.16 (0.83-1.63). Neither red wine nor total alcohol consumption were associated with prostate cancer risk in this population of moderate drinkers.

Total antioxidant intake and prostate cancer in the Cancer of the Prostate in Sweden (CAPS) study. A case control study

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Russnes, Kjell M.; Möller, Elisabeth; Wilson, Kathryn M.; Carlsen, Monica; Blomhoff, Rune; Smeland, Sigbjørn; Adami, Hans-Olov; Grönberg, Henrik; Mucci, Lorelei A.; Bälter, Katarina

2016-01-01

The total intake of dietary antioxidants may reduce prostate cancer risk but available data are sparse and the possible role of supplements unclear. We investigated the potential association between total and dietary antioxidant intake and prostate cancer in a Swedish population. We used FFQ data from 1499 cases and 1112 controls in the population based case–control study Cancer of the Prostate in Sweden (CAPS). The ferric reducing antioxidant potential (FRAP) assay was used to assess the total antioxidant capacity (TAC) of diet and supplements. We calculated odds ratios (ORs) for the risk of prostate cancer across quintiles of antioxidant intake from all foods, from fruit and vegetables only, and from dietary supplements using unconditional logistic regression. Coffee comprised 62 % of the dietary antioxidant intake, tea 4 %, berries 4 %, chocolate 2 %, and boiled potatoes 2 %. In total 19 % and 13 % of the population took multivitamins and supplemental Vitamin C respectively, on a regular basis. Antioxidant intake from all foods and from fruits and vegetables separately measured by the FRAP assay was not associated with prostate cancer risk. For antioxidant intake from supplements we found a positive association with total, advanced, localized, high grade and low grade prostate cancer in those above median supplemental TAC intake of users compared to non-users (Adjusted ORs for total prostate cancer: 1.37, 95 % CI 1.08–1.73, advanced: 1.51, 95 % CI 1.11–2.06, localized: 1.36. 95 % CI 1.06–1.76, high grade 1.60, 95 % CI 1.06–2.40, low grade 1.36, 95 % CI 1.03–1.81). A high intake of coffee (≥6 cups/day) was associated with a possible risk reduction of fatal and significantly with reduced risk for high grade prostate cancer, adjusted OR: 0.45 (95 % CI: 0.22–0.90), whereas a high intake of chocolate was positively associated with risk of total, advanced, localized and low grade disease (adjusted OR for total: 1.43, 95 % CI 1.12–1.82, advanced: 1

HUMAN PROSTATE CANCER RISK FACTORS

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Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

Alcohol consumption and prostate cancer: a mini review.

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Rizos, Ch; Papassava, M; Golias, Ch; Charalabopoulos, K

2010-07-01

Prostate cancer has become a major public health problem worldwide although the etiology of prostate cancer remains largely unknown. Dietary factors, dietary supplements, and physical activity might be important in the prevention of the disease. In the majority of studies published, it was observed that high consumption of meat, alcohol and dairy products has been linked to a greater risk. Specifically, alcohol use, and particularly heavy use, may cause cancers of liver, esophagus, larynx, pharynx and oral cavity, with risks for the aero-digestive cancers. Moderate use among women has been related with increases in breast cancer. Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal environment and in parallel, containing chemical substances such as flavonoids (red wine), may alter tumor cell growth. In this mini review, the relation between alcohol consumption and prostate cancer risk is analyzed.

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

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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)

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

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Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study.

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Papantoniou, Kyriaki; Castaño-Vinyals, Gemma; Espinosa, Ana; Aragonés, Nuria; Pérez-Gómez, Beatriz; Burgos, Javier; Gómez-Acebo, Inés; Llorca, Javier; Peiró, Rosana; Jimenez-Moleón, Jose Juan; Arredondo, Francisco; Tardón, Adonina; Pollan, Marina; Kogevinas, Manolis

2015-09-01

Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case-control study in Spain. We included 1,095 prostate cancer cases and 1,388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs. rotating, time schedules, duration, frequency), using lifetime occupational history. Sociodemographic and lifestyle factors were assessed by face-to-face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk [Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37] compared with never night workers; this risk increased with longer duration of exposure (≥ 28 years: OR 1.37; 95%CI 1.05, 1.81; p-trend = 0.047). Risks were more pronounced for high risk tumors [D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86], particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45; p-trend = 0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long-term night work. In this large population based study, we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis. © 2014 UICC.

Significance of common variants on human chromosome 8q24 in relation to the risk of prostate cancer in native Japanese men

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Hosoi Takayuki

2009-07-01

Full Text Available Abstract Background Common variants on human chromosome 8q24, rs1447295 (C/A and rs6983267 (T/G, have been recently linked to the prevalence of prostate cancer in European and American populations. Here, we evaluated whether the single-nucleotide polymorphisms rs1447295 and rs6983267 were associated with the risk of sporadic prostate cancer as well as latent prostate cancer in a native Japanese population. Results We analyzed genomic DNA samples from 391 sporadic prostate cancer patients, 323 controls who had died from causes unrelated to cancer and 112 Japanese men who were diagnosed as having latent prostate cancer based on autopsy results. The polymorphisms were determined by allelic discrimination using a fluorescent-based TaqMan assay. The A allele of rs1447295 was significantly associated with the risk of sporadic prostate cancer (p = 0.04; age-adjusted OR, 1.34, while the G allele of rs6983267 showed a trend towards being a high-risk allele (p = 0.06; age-adjusted OR, 1.27. No significant difference between these two polymorphisms and the risk of latent prostate cancer was observed in the present Japanese population. Conclusion Known variants on human chromosome 8q24 may be risk factors for sporadic prostate cancer in native Japanese men.

The influence of family history on prostate cancer risk : implications for clinical management

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Madersbacher, Stephan; Alcaraz, Antonio; Emberton, Mark; Hammerer, Peter; Ponholzer, Anton; Schroeder, Fritz H.; Tubaro, Andrea

A family history of prostate cancer has long been identified as an important risk factor for developing the disease. This risk factor can be easily assessed in clinical practice and current guidelines recommend to initiate prostate cancer early detection 5 years earlier (i.e. around the age of 40

Causes of Death in Men With Prevalent Diabetes and Newly Diagnosed High- Versus Favorable-Risk Prostate Cancer

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D'Amico, Anthony V.; Braccioforte, Michelle H.; Moran, Brian J.; Chen, Ming-Hui

2010-01-01

Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whether PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% CI, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa.

Boost first, eliminate systematic error, and individualize CTV to PTV margin when treating lymph nodes in high-risk prostate cancer

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Rossi, Peter J.; Schreibmann, Eduard; Jani, Ashesh B.; Master, Viraj A.; Johnstone, Peter A.S.

2009-01-01

Purpose: The purpose of this report is to evaluate the movement of the planning target volume (PTV) in relation to the pelvic lymph nodes (PLNs) during treatment of high-risk prostate cancer. Patients and methods: We reviewed the daily treatment course of ten consecutively treated patients with high-risk prostate cancer. PLNs were included in the initial PTV for each patient. Daily on-board imaging of gold fiducial markers implanted in the prostate was used; daily couch shifts were made as needed and recorded. We analyzed how the daily couch shifts impacted the dose delivered to the PLN. Results: A PLN clinical target volume was identified in each man using CT-based treatment planning. At treatment planning, median minimum planned dose to the PLN was 95%, maximum 101%, and mean 97%. Daily couch shifting to prostate markers degraded the dose slightly; median minimum dose to the PLN was 92%, maximum, 101%, and mean delivered, 96%. We found two cases, where daily systematic shifts resulted in an underdosing of the PLN by 9% and 29%, respectively. In other cases, daily shifts were random and led to a mean 2.2% degradation of planned to delivered PLN dose. Conclusions: We demonstrated degradation of the delivered dose to PLN PTV, which may occur if daily alignment only to the prostate is considered. To improve PLN PTV, it maybe preferable to deliver the prostate/boost treatment first, and adapt the PTV of the pelvic/nodal treatment to uncertainties documented during prostate/boost treatment

Prostate cancer and inflammation: the evidence

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Sfanos, Karen S; De Marzo, Angelo M

2014-01-01

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

Vitamins, metabolomics, and prostate cancer.

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Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2017-06-01

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

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Zapatero, Almudena, E-mail: azapatero.hlpr@salud.madrid.org [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Garcia-Vicente, Feliciano [Department of Medical Physics, Hospital Universitario de la Princesa, Madrid (Spain); Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile [Department of Radiation Oncology, Hospital Universitario de la Princesa, Madrid (Spain); Fernandez, Inmaculada; Rabadan, Mariano [Department of Urology, Hospital Universitario de la Princesa, Madrid (Spain)

2011-12-01

Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer.

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Chamie, Karim; DeVere White, Ralph W; Lee, Dennis; Ok, Joon-Ha; Ellison, Lars M

2008-11-01

%-15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%-17.7%) than unexposed men (4%; 95% CI, 0.5%-7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high-grade and metastatic disease on presentation. Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as 'high risk,' just like men of African-American heritage and men with a family history of prostate cancer.

Androgen receptor profiling predicts prostate cancer outcome

NARCIS (Netherlands)

S. Stelloo (Suzan); E. Nevedomskaya (Ekaterina); H.G. van der Poel (Henk G.); J. de Jong (Jeroen); G.J.H.L. Leenders (Geert); G.W. Jenster (Guido); L. Wessels (Lodewyk); A.M. Bergman (Andries); W. Zwart (Wilbert)

2015-01-01

textabstractProstate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer

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

Childhood Height and Birth Weight in Relation to Future Prostate Cancer Risk

DEFF Research Database (Denmark)

Cook, Michael B; Gamborg, Michael; Aarestrup, Julie

2013-01-01

Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We...

Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

Directory of Open Access Journals (Sweden)

Maurizio Valeriani

2014-01-01

Full Text Available Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT. Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI and genitourinary (GU toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P=0.04 in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P<0.001 for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

Early quality of life outcomes in patients with prostate cancer managed by high-dose-rate brachytherapy as monotherapy

International Nuclear Information System (INIS)

Komiya, Akira; Fujiuchi, Yasuyoshi; Ito, Takatoshi

2013-01-01

The purpose of this study was to evaluate the early quality of life outcomes in prostate cancer patients managed by high-dose-rate brachytherapy as monotherapy. A total of 51 patients with cT1c-T3aN0M0 prostate cancer treated between July 2007 and January 2010 were included in this study. The average age was 69?years, and the average initial serum prostate-specific antigen was 10.98?ng/mL. A total of 25, 18 and eight patients were considered to be low, intermediate and high risk, respectively. All patients received one implant of Ir-192 and seven fractions of 6.5?Gy within 3.5?days for a total prescribed dose of 45.5?Gy. For high-risk prostate cancer, neoadjuvant androgen deprivation therapy was carried out for at least 6?months, and continued after high-dose-rate brachytherapy. Quality of life outcomes were measured by using the International Prostate Symptom Score, the Functional Assessment of Cancer Therapy-Prostate and the International Index of Erectile Function Questionnaire. The oncological outcome was assessed by serum prostate-specific antigen and diagnostic imaging. Adverse events were also recorded. The Functional Assessment of Cancer Therapy-Prostate scores decreased for a few months after high-dose-rate brachytherapy, and recovered to pretreatment condition thereafter. The International Prostate Symptom Score significantly increased 2?weeks after treatment for each of its items and their sum, and it returned to baseline after 12?weeks. Sexual function decreased at 2 and 4?weeks, and recovered after 12?weeks. Severe complications were rare. Within a median follow up of 17.2?months, two patients showed a prostate-specific antigen recurrence. High-dose-rate brachytherapy for prostate cancer is a feasible treatment modality with acceptable toxicity and only a limited impact on the quality of life. (author)

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

DEFF Research Database (Denmark)

Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B.

2017-01-01

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks...

Rates and predictors of colorectal cancer screening by race among motivated men participating in a prostate cancer risk assessment program

Science.gov (United States)

Hall, Michael J.; Ruth, Karen; Giri, Veda N.

2011-01-01

Background Screening by fecal occult blood test and lower endoscopy have lowered colorectal cancer (CRC) mortality, but compliance gaps persist. Of concern are possible disparities in uptake of CRC screening between White and African American (AA) men. Our goal was to assess for disparities in uptake of CRC screening among men participating in a high-risk prostate cancer clinic. If present, such disparities could support hypotheses for further research examining racial differences in awareness and patient preferences in undergoing CRC screening. Methods Baseline data on a racially diverse cohort of men age 50–69 at increased risk of prostate cancer collected via the prostate cancer risk assessment program (PRAP) at Fox Chase Cancer Center were analyzed. Predictors of uptake of CRC screening were assessed using multivariable logistic regression. Results Compared to Whites, AA men had statistically significantly lower uptake of fecal occult blood testing (AA 49.0% vs White 60.7%, p=0.035), lower endoscopy (AA 44.1% vs White 58.5%, p=0.011), and any CRC screening (AA 66.2% vs White 76.3%, p=0.053). Predictors of uptake of lower endoscopy among AA men included older age (OR 3.61, 95% CI 1.87–6.97), family history of CRC (OR 3.47, 95% CI 1.30–9.25), and insurance status (OR 1.90, 95% CI 1.04–3.46). Conclusion Despite awareness of cancer risk and motivation to seek prostate cancer screening through a specialized prostate cancer risk assessment program, evidence supporting compliance gaps with CRC screening among men was found. Tailored messages to younger AA men with and without a family history of CRC are needed. PMID:21751189

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

Energy Technology Data Exchange (ETDEWEB)

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

Place of surgery in high-risk tumours of the prostate

International Nuclear Information System (INIS)

Soulie, M.; Rozet, F.; Hennequin, C.; Salomon, L.

2010-01-01

Among the different options recommended for high-risk prostate cancer, radical prostatectomy is admitted as radiotherapy, but its role is still controversial in mono-therapy and difficult to evaluate in combined treatments. The results of clinical trials combining an external radiotherapy to a long-term androgen deprivation in locally advanced tumours sustain the principle of a multidisciplinary management in high-risk prostate cancer. The impact of surgery on the risk of progression and local recurrence is important in selected patients with low grade and small tumoral volume. Clinical and histological data associated to the MRI assessment remain essential and enhance the preoperative multidisciplinary decision, especially regarding nodal and distant metastases. Radical prostatectomy with an extended pelvic lymphadenectomy can be considered as a viable alternative to radiotherapy and hormonal therapy in these patients with a long life expectancy but presenting a high risk of local progression and a low risk of metastatic disease. Morbidity of the procedure is similar to radical prostatectomy for organ-confined tumours despite more erectile dysfunction due to non-sparing radical prostatectomy in most of cases. Oncological results from recent compiled series show 10- and 15-year specific survival rates around 85 and 75%, respectively, including adjuvant or salvage treatments with radiotherapy, androgen deprivation or chemotherapy. (authors)

Strong Signature of Natural Selection within an FHIT Intron Implicated in Prostate Cancer Risk

Science.gov (United States)

Ding, Yan; Larson, Garrett; Rivas, Guillermo; Lundberg, Cathryn; Geller, Louis; Ouyang, Ching; Weitzel, Jeffrey; Archambeau, John; Slater, Jerry; Daly, Mary B.; Benson, Al B.; Kirkwood, John M.; O'Dwyer, Peter J.; Sutphen, Rebecca; Stewart, James A.; Johnson, David; Nordborg, Magnus; Krontiris, Theodore G.

2008-01-01

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, re-sequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D = 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. PMID:18953408

Whole-Pelvis Radiotherapy in Combination With Interstitial Brachytherapy: Does Coverage of the Pelvic Lymph Nodes Improve Treatment Outcome in High-Risk Prostate Cancer?

International Nuclear Information System (INIS)

Bittner, Nathan; Merrick, Gregory S.; Wallner, Kent E.; Butler, Wayne M.; Galbreath, Robert; Adamovich, Edward

2010-01-01

Purpose: To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field. Methods and Materials: From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of ≥8 and/or a prostate-specific antigen (PSA) concentration of ≥20 ng/ml. Results: With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 91.7% vs. 84.4% (p = 0.126), 95.5% vs. 92.6% (p = 0.515), and 79.5% vs. 67.1% (p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% (p = 0.413), 94.2% vs. 96.0% (p = 0.927), and 73.7% vs. 70.2% (p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% (p = 0.639), 100% vs. 88% (p = 0.198), and 87.5% vs. 58.8% (p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results. Conclusions: For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naive patients, for whom a significant improvement in OS was observed.

The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: A meta-analysis

Science.gov (United States)

Chua, Michael E.; Sio, Maria Christina D.; Sorongon, Mishell C.; Morales, Marcelino L.

2013-01-01

Objective: Our objective was to systematically analyze the evidence for an association between serum level long chain omega-3 polyunsaturated fatty acid (n-3 PUFA) and prostate cancer risk from human epidemiological studies. Study Procedures: We searched biomedical literature databases up to November 2011 and included epidemiological studies with description of long chain n-3 PUFA and incidence of prostate cancer in humans. Critical appraisal was done by two independent reviewers. Data were pooled using the general variance-based method with random-effects model; effect estimates were expressed as risk ratio with 95% confidence interval (CI). Heterogeneity was assessed by Chi2 and quantified by I2, publication bias was also determined. Results: In total, 12 studies were included. Significant negative association was noted between high serum level of n-3 PUFA doc-osapentaenoic acid (DPA) and total prostate cancer risk (RR:0.756; 95% CI 0.599, 0.955; p = 0.019). Likewise, a positive association between high blood level of fish oil contents, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and high-grade prostate tumour incidence (RR:1.381; 95% CI 1.050, 1.817; p = 0.021) was noted; however, this finding was evident only after adjustment was done on interstudy variability through the removal of a lower quality study from the pool. Conclusions: High serum levels of long chain n-3 PUFA DPA is associated with reduced total prostate cancer risk. While high blood level of EPA and DHA is possibly associated with increased high-grade prostate tumour risk. PMID:23766835

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

Directory of Open Access Journals (Sweden)

Lucio Dell'Atti

Full Text Available ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa after a high-grade prostatic intraepithelial neoplasia (HGPIN diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4% patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001, Gleason score distribution (p<0.001, and number of positive biopsy cores (p<0.002 between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001. Moreover, increasing duration of metformin assumption (≥2 years was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Petereit, Daniel G. [Department of Radiation Oncology, John T. Vucurevich Regional Cancer Care Institute, Rapid City Regional Hospital, Rapid City, SD (United States); Hong, Theodore S.; Tome, Wolfgang [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Ritter, Mark A., E-mail: ritter@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States)

2012-01-01

Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

Dietary Phytoestrogens and Prostate Cancer Prevention

National Research Council Canada - National Science Library

Kurzer, Mindy S; Slaton, Joel

2007-01-01

The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study.

Directory of Open Access Journals (Sweden)

Vincent J Gnanapragasam

2016-08-01

Full Text Available Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score.Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer. The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM. An external validation cohort (n = 1,706 was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator. Using this approach, a

Prostate cancer risk prediction based on complete prostate cancer family history

OpenAIRE

Albright, Frederick; Stephenson, Robert A; Agarwal, Neeraj; Teerlink, Craig C; Lowrance, William T; Farnham, James M; Albright, Lisa A Cannon

2014-01-01

Background Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. Methods A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from ma...

Flavonoids intake and risk of prostate cancer: a meta-analysis of observational studies.

Science.gov (United States)

Guo, K; Liang, Z; Liu, L; Li, F; Wang, H

2016-12-01

The aim of the study was to assess the association between total flavonoids/flavonoid subclasses intake and prostate cancer risk. Several databases were searched to select eligible studies with predefined criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the effect size. Publication bias and sensitivity analysis were performed. A total of five studies including four prospective cohort studies and one case-control study were included in the meta-analysis. The pooled result demonstrated a significantly increased risk of prostate cancer with higher intake of total flavonoids (RR = 1.12, 95% CI: 1.02-1.23, P = 0.013). However, sensitivity analysis indicated that there lacked a significant association after removing the study of Wang et al. (RR = 1.17, 95% CI: 0.94-1.46). Subgroup analysis stratified by flavonoids subclasses found that higher intake of anthocyanidins and flavan-3-ols were significantly associated with increased prostate cancer risk (RR = 1.12, 95% CI: 1.03-1.21, P = 0.011; RR = 1.21, 95% CI: 1.10-1.32, P flavonoids may not be associated with prostate cancer risk. © 2016 Blackwell Verlag GmbH.

Prostate cancer epigenome.

Science.gov (United States)

Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J; Chaudhary, Jaideep

2015-01-01

Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome.

Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

DEFF Research Database (Denmark)

Song, H.; Koessler, T.; Ahmed, S.

2008-01-01

allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

Directory of Open Access Journals (Sweden)

Bjartell Anders

2011-09-01

Full Text Available Abstract Background High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. Findings Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR (HR 0.56, 95% CI: 0.34-0.93, p = 0.024 and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021. These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression. Conclusion Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.

Directory of Open Access Journals (Sweden)

Sara Lindstrom

2011-02-01

Full Text Available Genome-wide association studies (GWAS have identified multiple single nucleotide polymorphisms (SNPs associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10⁻²⁸. Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test, where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade < 8 tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study.

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Dutta, Anupriya; Uno, Hajime; Holman, Alex; Lorenz, David R; Gabuzda, Dana

2017-07-01

African American men have the highest incidence of prostate cancer among ethnic groups, and racial disparity is highest in younger men. Prostate cancer prevalence is rising in HIV-infected men due to improved survival on antiretroviral therapies, yet little is known about racial differences in prostate cancer risk by HIV-infection status and age. This is a prospective cohort study of prostate cancer risk in 2,800 HIV-infected and -uninfected men who have sex with men (MSM) aged 40-70 years (22% African American) who were enrolled in the multicenter AIDS cohort study from 1996 to 2010. Poisson regression models were used to examine associations between race and HIV-infection status and prostate cancer risk among men aged 40-70, 40-55, and 56-70 years. Among men aged 40-70 years, incidence rates (IR) per 100,000 person-years were 169 among all men and 276 among African American HIV-infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0, 95% CI 0.55-1.82), but nearly threefold higher in African Americans compared to non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36-5.18 and 1.27-8.16 for all or HIV-infected men, respectively). Racial disparity in prostate cancer risk was greatest in African American men aged 40-55 years (adjusted IRR 3.31, 95% CI 1.19-9.22). Prostate cancer risk showed associations with family history of prostate cancer (p = 0.001), but not heavy smoking, androgen supplement use, or HIV-related factors. Among MSM, African American HIV-positive and HIV-negative men aged 40-55 years have threefold increased risk of young-onset prostate cancer compared to non-African American men, highlighting the need to make informed decisions about screening in this population.

Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models.

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Pounis, George; Tabolacci, Claudio; Costanzo, Simona; Cordella, Martina; Bonaccio, Marialaura; Rago, Livia; D'Arcangelo, Daniela; Filippo Di Castelnuovo, Augusto; de Gaetano, Giovanni; Donati, Maria Benedetta; Iacoviello, Licia; Facchiano, Francesco

2017-07-01

Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p 3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0-2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results. © 2017 UICC.

Diffusion-weighted MRI for detecting prostate tumour in men at increased genetic risk

International Nuclear Information System (INIS)

Souza, Nandita M. de; Morgan, Veronica A.; Bancroft, Elizabeth; Sohaib, S. Aslam; Giles, Sharon L.; Kote-Jarai, Zsofia; Castro, Elena; Hazell, Steven; Jafar, Maysam; Eeles, Rosalind

2014-01-01

•Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening.•MRI is specific for detecting prostate cancer in men with increased genetic risk.•Detection of prostate cancer in men at genetically low risk with MRI is limited. Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening. MRI is specific for detecting prostate cancer in men with increased genetic risk. Detection of prostate cancer in men at genetically low risk with MRI is limited. Diffusion-weighted (DW)-MRI is invaluable in detecting prostate cancer. We determined its sensitivity and specificity and established interobserver agreement for detecting tumour in men with a family history of prostate cancer stratified by genetic risk. 51 men with a family history of prostate cancer underwent T2-W + DW-endorectal MRI at 3.0 T. Presence of tumour was noted at right and left apex, mid and basal prostate sextants by 2 independent observers, 1 experienced and the other inexperienced in endorectal MRI. Sensitivity and specificity against a 10-core sampling technique (lateral and medial cores at each level considered together) in men with >2× population risk based on 71 SNP analysis versus those with lower genetic risk scores was established. Interobserver agreement was determined at a subject level. Biopsies indicated cancer in 28 sextants in 13/51 men; 32 of 51 men had twice the population risk (>0.25) based on 71 SNP profiling. Sensitivity/specificity per-subject for patients was 90.0%/86.4% (high-risk) vs. 66.7%/100% (low-risk, observer 1) and 60.0%/86.3% (high-risk) vs. 33.3%/93.8% (low-risk, observer 2) with moderate overall inter-observer agreement (kappa = 0.42). Regional sensitivities/specificities for high-risk vs. low-risk for observer 1 apex 72.2%/100% [33.3%/100%], mid 100%/93.1% [100%/97.3%], base 16.7%/98.3% [0%/100%] and for observer 2 apex 36.4%/98.1% [0%/100%], mid 28.6%/96.5% [100%/100%], base 20%/100% [0%/97.3%] were poorer as they failed to detect

Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial.

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Blanchard, Pierre; Faivre, Laura; Lesaunier, François; Salem, Naji; Mesgouez-Nebout, Nathalie; Deniau-Alexandre, Elisabeth; Rolland, Frédéric; Ferrero, Jean-Marc; Houédé, Nadine; Mourey, Loïc; Théodore, Christine; Krakowski, Ivan; Berdah, Jean-François; Baciuchka, Marjorie; Laguerre, Brigitte; Davin, Jean-Louis; Habibian, Muriel; Culine, Stéphane; Laplanche, Agnès; Fizazi, Karim

2016-01-01

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS). A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (PENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic variation in the HSD17B1 gene and risk of prostate cancer.

Directory of Open Access Journals (Sweden)

Peter Kraft

2005-11-01

Full Text Available Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002 inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

Science.gov (United States)

van Leeuwen, Pim J; Hayen, Andrew; Thompson, James E; Moses, Daniel; Shnier, Ron; Böhm, Maret; Abuodha, Magdaline; Haynes, Anne-Maree; Ting, Francis; Barentsz, Jelle; Roobol, Monique; Vass, Justin; Rasiah, Krishan; Delprado, Warick; Stricker, Phillip D

2017-12-01

To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P prostate cancer. Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

International Nuclear Information System (INIS)

Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

2008-01-01

Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

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Ferrer-Batallé, Montserrat; Llop, Esther; Ramírez, Manel; Aleixandre, Rosa Núria; Saez, Marc; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2017-04-17

Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

Dietary Fat, Fat Metabolizing Genes, and Prostate Cancer Risk in African-Americans and Whites

National Research Council Canada - National Science Library

Ingles, Sue A

2004-01-01

.... We are examining whether genetic variants in the n-6 fatty acid LOX pathways are associated with the risk of prostate cancer in a population-based case control study of advanced prostate cancer among...

Natural History of Clinically Staged Low- and Intermediate-Risk Prostate Cancer Treated With Monotherapeutic Permanent Interstitial Brachytherapy

International Nuclear Information System (INIS)

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Wallner, Kent E.; Butler, Wayne M.

2010-01-01

Purpose: To evaluate the natural history of clinically staged low- and intermediate-risk prostate cancer treated with permanent interstitial seed implants as monotherapy. Methods and Materials: Between April 1995 and May 2005, 463 patients with clinically localized prostate cancer underwent brachytherapy as the sole definitive treatment. Men who received supplemental external beam radiotherapy or androgen deprivation therapy were excluded. Dosimetric implant quality was determined based on the minimum dose that covered 90% of the target volume and the volume of the prostate gland receiving 100% of the prescribed dose. Multiple parameters were evaluated as predictors of treatment outcomes. Results: The 12-year biochemical progression-free survival (bPFS), cause-specific survival, and overall survival rates for the entire cohort were 97.1%, 99.7%, and 75.4%, respectively. Only pretreatment prostate-specific antigen level, percent positive biopsy cores, and minimum dose that covered 90% of the target volume were significant predictors of biochemical recurrence. The bPFS, cause-specific survival, and overall survival rates were 97.4%, 99.6%, and 76.2%, respectively, for low-risk patients and 96.4%, 100%, and 74.0%, respectively, for intermediate-risk patients. The bPFS rate was 98.8% for low-risk patients with high-quality implants versus 92.1% for those with less adequate implants (p < 0.01), and it was 98.3% for intermediate-risk patients with high-quality implants versus 86.4% for those with less adequate implants (p < 0.01). Conclusions: High-quality brachytherapy implants as monotherapy can provide excellent outcomes for men with clinically staged low- and intermediate-risk prostate cancer. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups.

Familial risks of breast and prostate cancers: does the definition of the at risk period matter?

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Brandt, Andreas; Bermejo, Justo Lorenzo; Sundquist, Jan; Hemminki, Kari

2010-03-01

'Being at familial risk' may have different connotations in studies on familial risk of cancer. The register-based definition of a family history considers individuals with an affected relative at familial risk independently of the family member's diagnostic time. Alternatively, the individuals are classified to be at familial risk only after the diagnosis date of their relative, relevant to clinical counselling and screening situations. The aim of this study was to compare familial breast and prostate cancer risks according to the two definitions. The nationwide Swedish Family-Cancer Database with information on cancers from 1958 to 2006 was used to calculate the hazard ratio of breast and prostate cancers according to family history using Cox regression. Family history was defined considering the number and type of affected relatives and the relative's diagnostic age, respectively. Individuals were considered at familial risk from their entry to the study or, alternatively, from the diagnostic time of the relative. Hazard ratios were equal whether individuals were considered at risk independent of the relative's diagnostic date or only after the relative's diagnostic date. These results indicate that studies on familial breast or prostate cancer risk which do not take the relative's diagnosis date into account are applicable to screening and clinical counselling situations. The estimates according to the register-based definition are based on larger numbers of patients, which may be crucial for analysis of small groups such as families of multiple cases. Copyright 2009 Elsevier Ltd. All rights reserved.

Postoperative Intensity Modulated Radiation Therapy in High Risk Prostate Cancer: A Dosimetric Comparison

International Nuclear Information System (INIS)

Digesu, Cinzia; Cilla, Savino; De Gaetano, Andrea; Massaccesi, Mariangela; Macchia, Gabriella; Ippolito, Edy; Deodato, Francesco; Panunzi, Simona; Iapalucci, Chiara; Mattiucci, Gian Carlo; D'Angelo, Elisa; Padula, Gilbert D.A.; Valentini, Vincenzo; Cellini, Numa

2011-01-01

The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT.

Feasibility and early outcome of high-dose-rate Ir-192 brachytherapy as monotherapy in two fractions within 1 day for high-/very high-risk prostate cancer.

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Ashida, Shingo; Yamasaki, Ichiro; Tamura, Kenji; Shimamoto, Tsutomu; Inoue, Keiji; Kariya, Shinji; Kobayashi, Kana; Yamagami, Takuji; Shuin, Taro

2016-05-01

The aim of the present study was to evaluate the feasibility and preliminary outcomes of high-dose-rate (HDR)-brachytherapy as a monotherapy in two fractions within 1 day for localized prostate cancer, including high-/very high-risk cases. Among the 68 patients treated with HDR monotherapy between July 2011 and December 2014, 65 had a minimal follow-up of 12 months without adjuvant androgen deprivation therapy and were enrolled in the present study [42/65 (64.6%) exhibited high-/very high-risk diseases]. HDR monotherapy was performed in two fractions with a minimal interval of 6 h and the prescribed dose was 13.5 Gy (×2). Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (version 4; http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40), and biochemical failure was assessed by the Phoenix definition. The median follow-up time was 30.1 months. The majority of patients had Grade 0-1 acute AEs. Four patients (6.2%) exhibited urinary retention, requiring a Foley catheter. Grade 3 acute AEs occurred at a frequency of 3.1% and hematuria at 1.5%. The majority of patients also exhibited Grade 0-1 chronic AEs. Grade 3 chronic AEs occurred at a frequency of 1.5% and urethral stricture at 1.5%, for which endoscopic treatment was indicated. Acute and chronic gastrointestinal AEs were uncommon, and no Grade 3 or above AEs developed. Biochemical failure occurred in 4 patients who all exhibited high-/very high-risk diseases. Kaplan-Meier estimated that 3 year biochemical failure-free survival was 91.6% overall and 88.0% in high-/very high-risk cases. The present two-fraction 1 day HDR monotherapy is feasible with minimal AEs and achieved acceptable biochemical control of localized prostate cancer, including high-/very high-risk cases, although long-term follow-up is required.

Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case–control study

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Boxall, Naomi; Bennett, Dimitri; Hunger, Matthias; Dolin, Paul; Thompson, Paula L

2016-01-01

Objectives Investigate potential association between pioglitazone exposure and risk of prostate cancer. Research design and methods Nested, matched case–control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. Results From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (pworld, nested matched case–control study, exposure to pioglitazone was not associated with increased risk of prostate cancer. PMID:28074141

Lifetime total and beverage specific - alcohol intake and prostate cancer risk: a case-control study

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Carruba Giuseppe

2004-12-01

Full Text Available Abstract Background We investigated lifetime alcohol consumption and prostate cancer risk in a case-control study conducted in Buffalo, NY (1998–2001. Methods The study included 88 men, aged 45 to 85 years with incident, histologically-confirmed prostate cancer and 272 controls. We conducted extensive in-person interviews regarding lifetime alcohol consumption and other epidemiologic data. Results Prostate cancer risk was not associated with lifetime intake of total and beverage specific ethanol. In addition we found no association with number of drinks per day (average drinks per day over the lifetime or drinks per drinking day (average drinks per day on drinking days only over the lifetime. However, we observed an inverse association with the total number of drinking years. Men in the lowest tertile of total drinking years had a two-fold prostate cancer risk than men in the highest tertile (OR 2.16, 95% CI 0.98–4.78, p for trend Conclusion Our results suggest that alcohol intake distribution across lifetime may play a more important role in prostate cancer etiology than total lifetime consumption.

Should abdominal sequences be included in prostate cancer MR staging studies?

International Nuclear Information System (INIS)

McEvoy, S.H.; Lavelle, L.P.; Purcell, Y.M.; Quinlan, D.M.; Skehan, S.J.; Collins, C.D.; McMahon, C.J.

2015-01-01

Highlights: • ESUR guideline that abdominal MR sequences are reserved for high-risk prostate cancer is tested. • Routine abdominal sequences are of low yield in prostate cancer MR staging. • Routine abdominal staging sequences frequently result in incidental findings. • Abdominal staging sequences should be reserved for high-risk prostate cancer cases. - Abstract: Objectives: Prostate cancer staging MR examinations commonly include abdominal sequences to assess for non-regional (common iliac or para-aortic) nodal metastasis. In our experience the diagnostic yield of this is limited, but incidental findings are frequent, often necessitating further investigations. The aim of this study is to assess the diagnostic utility of abdominal sequences in routine prostate cancer MR staging studies. Methods: Findings on abdominal sequences of consecutive MRI prostate studies performed for staging newly diagnosed prostate cancer between September 2011 and September 2013 were reviewed with respect to adenopathy and additional incidental findings. Results were correlated with Gleason grade and serum prostate-specific antigen (PSA) level in each case. Results: 355 MRI prostate examinations were reviewed. 4 (1.1%) showed enlarged non-regional lymph nodes. Incidental findings were found in 82(23.1%) cases, neccessitating further investigation in 45 (12.7%) cases. Enlarged non-regional nodes were associated with higher PSA level and Gleason grade (p = 0.007, p = 0.005 respectively). With a combined threshold of PSA > 20 ng/mL and/or Gleason grade ≥8 the sensitivity, specificity, PPV and NPV were 100, 60, 3 and 100% respectively for predicting the presence of non-regional adenopathy. Conclusions: Routine abdominal sequences are of very low yield in routine prostate cancer MR staging, frequently resulting in incidental findings requiring further work-up and should be reserved for high-risk cases. Our experience supports the use of an abdominal staging sequence in high-risk

103PD brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma

International Nuclear Information System (INIS)

Dattoli, Michael; Wallner, Kent; Sorace, Richard; Koval, John; Cash, Jennifer; Acosta, Rudolph; Brown, Charles; Etheridge, James; Binder, Michael; Brunelle, Richard; Kirwan, Novelle; Sanchez, Servando; Stein, Douglas; Wasserman, Stuart

1996-01-01

Purpose: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium ( 103 Pd) boost for clinically localized high-risk prostate carcinoma. Methods and Materials: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) >15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103 Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal 103 Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable

Radiation therapy for prostate cancer

International Nuclear Information System (INIS)

Nakamura, Katsumasa

2001-01-01

In Japan, where the mortality rate of prostate cancer is lower than in Western countries, radical prostatectomy or hormonal therapy has been applied more frequently than radiation therapy. However, the number of patients with prostate cancer has been increasing recently and the importance of radiation therapy has rapidly been recognized. Although there have been no randomized trials, results from several institutions in Western countries suggest that similar results of cancer control are achieved with either radiation therapy or radical prostatectomy. For higher-risk cases, conformal high-dose therapy or adjuvant hormonal therapy is more appropriate. In this article, the results of radiation therapy for prostate cancer were reviewed, with a view to the appropriate choice of therapy in Japan. (author)

Are food patterns associated with prostate cancer in Jamaican men: a preliminary report.

Science.gov (United States)

Jackson, Maria; Walker, Susan; Simpson, Candace; McFarlane-Anderson, Norma; Bennett, Franklyn

2009-02-10

Morbidity and mortality data highlight prostate cancer as the most commonly diagnosed neoplasm in Jamaican males. This report examines the association between dietary patterns and risk of prostate cancer in Jamaican men. Case-control study of 204 histologically confirmed newly diagnosed prostate cancer cases and 204 individually matched urology clinic controls in Jamaica, 2004 - 2007. Diet was assessed by food frequency questionnaire. Factor analysis yielded four dietary patterns: (i) a "healthy" pattern of vegetables, fruits and peas and beans, (ii) a "carbohydrate" pattern with high loadings for white bread and refined cereals, (iii) "sugary foods and sweet baked products" pattern and (iv) a "organ meat and fast food pattern" with high loadings for high fat dessert, organ meat, fast food and salty snacks.Logistic regressions with the individual dietary patterns controlling for potential confounders showed no association between any of the food patterns and risk of prostate cancer. The healthy pattern showed an inverse non-significant association, whereas the carbohydrate pattern was positively and insignificantly related to prostate cancer. Analysis of all food patterns adjusting for each other revealed no association between food patterns and the risk of prostate cancer. Dietary patterns identified in our sample were not associated with risk of prostate cancer. Further investigations that better define cancer-free subjects and dietary measurements are needed to examine diet and prostate cancer outcomes.

Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events

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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

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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.

The Prevalence of Cardiac Risk Factors in Men with Localized Prostate Cancer Undergoing Androgen Deprivation Therapy in British Columbia, Canada

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Margot K. Davis

2015-01-01

Full Text Available Background. While androgen deprivation therapy (ADT reduces the risk of prostate cancer-specific mortality in high-risk localized prostate cancer, it adversely affects cardiovascular (CV risk factor profiles in treated men. Methods. We retrospectively reviewed the charts of 100 consecutive men with intermediate- or high-risk localized prostate cancer referred to the British Columbia Cancer Agency for ADT. Data on CV risk factors and disease were collected and Framingham risk scores were calculated. Results. The median age of the study cohort was 73 years. Established cardiovascular disease was present in 25% of patients. Among patients without established CV disease, calculated Framingham risk was high in 65%, intermediate in 33%, and low in 1%. Baseline hypertension was present in 58% of patients, dyslipidemia in 51%, and diabetes or impaired glucose tolerance in 24%. Hypertension was more prevalent in the study cohort than in an age- and sex-matched population sample (OR 1.74, P=0.006; diabetes had a similar prevalence (OR 0.93, P=0.8. Conclusions. Patients receiving ADT have a high prevalence of cardiovascular disease and risk factors and are more likely to be hypertensive than population controls. Low rates of CV risk screening suggest opportunities for improved primary and secondary prevention of CV disease in this population.

Prostate cancer outcome in Burkina Faso

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Yameogo Clotaire

2011-09-01

Full Text Available Abstract Introduction African-American black men race is one of non-modifiable risk factors confirmed for prostate cancer. Many studies have been done in USA among African- American population to evaluate prostate cancer disparities. Compared to the USA very few data are available for prostate cancer in Sub-Saharan African countries. The objective of this study was to describe incident prostate cancer (PC diagnosis characteristics in Burkina Faso (West Africa. Methods We performed a prospective non randomized patient’s cohort study of new prostate cancer cases diagnosed by histological analysis of transrectal prostate biopsies in Burkina Faso. Study participants included 166 patients recruited at the urology division of the university hospital of Ouagadougou. Age of the patients, clinical symptoms, digital rectal examination (DRE result, serum prostate-specific antigen (PSA level, histological characteristics and TNM classification were taking in account in this study. Results 166 transrectal prostate biopsies (TRPB were performed based on high PSA level or abnormal DRE. The prostate cancer rate on those TRPB was 63, 8 % (n=106. The mean age of the patients was 71, 5 years (52 to 86. Urinary retention was the first clinical patterns of reference in our institution (55, 7 %, n = 59. Most patients, 56, 6 % (n = 60 had a serum PSA level over than 100 ng/ml. All the patients had adenocarcinoma on histological study of prostate biopsy cores. The majority of cases (54, 7 % n = 58 had Gleason score equal or higher than 7. Conclusion Prostate cancer is diagnosed at later stages in our country. Very high serum PSA level and poorly differentiated tumors are the two major characteristics of PC at the time of diagnosis.

Association between polymorphisms in selected inflammatory response genes and the risk of prostate cancer

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Chen J

2016-01-01

Full Text Available Jun Chen,1,* Xue-Ming Ying,2,* Xue-Ming Huang,3 Peng Huang,4 Shao-Cong Yan1 1Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Oncology, Jingdezhen City People’s Hospital, Jingdezhen, 3Department of Urology, Research Institute, The First Affiliated Hospital of Nanchang University, 4The Medical School of Nanchang University, School of Public Health, Nanchang, People’s Republic of China*These authors contributed equally to this workAbstract: Inflammation represents an important event which facilitates prostate carcinogenesis. Genetic variations in inflammatory response genes could affect the level and function of the protein products, resulting in the differential prostate cancer risk among carriers of different variants. This study attempted to investigate the association of IL-4 rs2243250, IL-6 rs10499563, IL-8 rs4073, as well as NFKBIA rs2233406 and rs3138053 polymorphisms with prostate cancer risk in the Chinese population. Genotyping of the polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism technique on 439 prostate cancer patients and 524 controls, and the association of each polymorphic genotype with prostate cancer risk was evaluated by using logistic regression analysis based on allele, heterozygous, and homozygous comparison models, with adjustment to age and smoking status. We showed that the C allele of IL-4 rs2243250 polymorphism could increase prostate cancer risk (heterozygous comparison model: odds ratio [OR] =1.434, 95% confidence interval [CI] =1.092–1.881, P=0.009; homozygous comparison model: OR =2.301, 95% CI =1.402–3.775, P=0.001; allele comparison model: OR =1.509, 95% CI =1.228–1.853, P<0.001. On the other hand, the C allele of rs10499563 polymorphism could decrease prostate cancer risk (heterozygous comparison model: OR =0.694, 95% CI =0.525–0.918, P=0.010; homozygous comparison model: OR =0.499, 95% CI =0

Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers.

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Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

2013-07-25

Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy.

Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers

International Nuclear Information System (INIS)

Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

2013-01-01

Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy

Specialty Supplements and Prostate Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort

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Brasky, Theodore M.; Kristal, Alan R.; Navarro, Sandi L.; Lampe, Johanna W.; Patterson, Ruth E.; Peters, Ulrike; White, Emily

2011-01-01

Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have anti-inflammatory, anti-oxidant, or other anti-cancer properties, few epidemiologic studies have examined the association between non-vitamin, non-mineral, “specialty” supplement use and prostate cancer risk. Participants, 50–76 years, were 35,239 male members of the VITamins And Lifestyle (VITAL) cohort who were residents of western Washington State, and who completed an extensive baseline questionnaire in 2000–2002. Participants responded about their frequency (days/week) and duration (years) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40–0.86) reduced risk of total prostate cancer. There were no associations for use of chondroitin, co-enzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent, however as current evidence is limited, it should not yet be promoted for prevention of prostate cancer. PMID:21598177

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk.

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Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A; Gupta, Nilesh S; Tang, Deliang; Rybicki, Benjamin A

2017-06-01

Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias toward the null in epidemiologic studies of over-all risk. Within a cohort of 6692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP, and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95%CI 1.01, 1.97), and obese status (OR = 1.59; 95%CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95%CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95%CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95%CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. In studies of obesity and PCa, differences in prostate volume cause a bias toward the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. © 2017 Wiley Periodicals, Inc.

Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer?

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Kishan, Amar U; Duchesne, Gillian; Wang, Pin-Chieh; Rwigema, Jean-Claude M; Saigal, Christopher; Rettig, Matthew; Steinberg, Michael L; King, Christopher R

2018-06-01

The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence. A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers. One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005). Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias.

Contemporary management of men with high-risk localized prostate cancer in the United States.

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Weiner, A B; Matulewicz, R S; Schaeffer, E M; Liauw, S L; Feinglass, J M; Eggener, S E

2017-09-01

Surgery and radiation-based therapies are standard management options for men with clinically localized high-risk prostate cancer (PCa). Contemporary patterns of care are unknown. We hypothesize the use of surgery has steadily increased in more recent years. Using the National Cancer Data Base for 2004-2013, all men diagnosed with high-risk localized PCa were identified using National Comprehensive Cancer Network criteria. Temporal trends in initial management were assessed. Multivariable logistic regression was used to evaluate demographic and clinical factors associated with undergoing radical prostatectomy (RP). In total, 127 391 men were identified. Use of RP increased from 26% in 2004 to 42% in 2013 (adjusted risk ratio (RR) 1.51, 95% CI 1.42-1.60, P<0.001), while external beam radiation therapy (EBRT) decreased from 49% to 42% (P<0.001). African American men had lower odds of undergoing RP (unadjusted rate of 28%, adjusted RR 0.69, 95% CI 0.66-0.72, <0.001) compared to White men (37%). Age was inversely associated with likelihood of receiving RP. Having private insurance was significantly associated with the increased use of RP (vs Medicare, adjusted odds ratio 1.04, 95% CI 1.01-1.08, P=0.015). Biopsy Gleason scores 8-10 with and without any primary Gleason 5 pattern were associated with decreased odds of RP (vs Gleason score ⩽6, both P<0.001). Academic and comprehensive cancer centers were more likely to perform RP compared to community hospitals (both P<0.001). The likelihood of receiving RP for high-risk PCa dramatically increased from 2004 to 2013. By 2013, the use of RP and EBRT were similar. African American men, elderly men and those without private insurance were less likely to receive RP.

Definition and Validation of “Favorable High-Risk Prostate Cancer”: Implications for Personalizing Treatment of Radiation-Managed Patients

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Muralidhar, Vinayak [Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts (United States); Chen, Ming-Hui [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Reznor, Gally [Center for Surgery and Public Health, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Moran, Brian J.; Braccioforte, Michelle H. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); Beard, Clair J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Choueiri, Toni K. [Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Martin, Neil E. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Sweeney, Christopher J. [Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Department of Urology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

2015-11-15

Purpose: To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease. Methods and Materials: We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen <10 ng/mL or Gleason 6 and prostate-specific antigen >20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancer–specific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Results: Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P=.049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P=.710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P<.001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P=.268). Conclusions: Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease.

Vietnam military service history and prostate cancer

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Fritschi Lin

2006-03-01

Full Text Available Abstract Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06. An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00 or brothers (OR = 2.05; 95% CI 1.20–3.50 diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer.

Prostate cancer risk profiles of Asian-American men: disentangling the effects of immigration status and race/ethnicity.

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Lichtensztajn, Daphne Y; Gomez, Scarlett Lin; Sieh, Weiva; Chung, Benjamin I; Cheng, Iona; Brooks, James D

2014-04-01

Asian-American men with prostate cancer have been reported to present with higher grade and later stage disease than white American men. However, Asian-American men comprise a heterogeneous population with distinct health outcomes. We compared prostate cancer risk profiles among the diverse racial and ethnic groups in California. We used data from the California Cancer Registry on 90,845 nonHispanic white, nonHispanic black and Asian-American men diagnosed with prostate cancer between 2004 and 2010. Patients were categorized into low, intermediate and high risk groups based on clinical stage, Gleason score and prostate specific antigen at diagnosis. Using polytomous logistic regression we estimated adjusted ORs for the association of race/ethnicity and nativity with risk group. In addition to the nonHispanic black population, 6 Asian-American groups (United States born Chinese, foreign born Chinese, United States born Japanese, foreign born Japanese, foreign born Filipino and foreign born Vietnamese) were more likely to have an unfavorable risk profile compared to nonHispanic white men. The OR for high vs intermediate risk disease ranged from 1.23 (95% CI 1.02-1.49) for United States born Japanese men to 1.45 (95% CI 1.31-1.60) for foreign born Filipino men. These associations appeared to be driven by higher grade and prostate specific antigen rather than by advanced clinical stage at diagnosis. In this large, ethnically diverse, population based cohort Asian-American men were more likely to have an unfavorable risk profile at diagnosis. This association varied by racial/ethnic group and nativity, and was not attributable to later stage at diagnosis. This suggests that Asian men may have biological differences that predispose to more severe disease. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Risk of prostate and bladder cancers in patients with spinal cord injury: a population-based cohort study.

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Lee, Wen-Yuan; Sun, Li-Min; Lin, Cheng-Li; Liang, Ji-An; Chang, Yen-Jung; Sung, Fung-Chang; Kao, Chia-Hung

2014-01-01

To evaluate the risk of prostate and bladder cancers in patients with spinal cord injury (SCI). We used data obtained from the National Health Insurance system of Taiwan for this study. The SCI cohort contained 54,401 patients with SCI, and each patient was randomly frequency matched with 4 people from the general population (without SCI) based on age, sex, and index date. Incidence rates, SCI cohort to non-SCI cohort rate ratios, and hazard ratios were measured to evaluate the cancer risks. Patients with SCI showed a significantly lower risk of developing prostate cancer compared with subjects without SCI (adjusted hazard ratio = 0.73; 95% confidence interval = 0.59, 0.90), after accounting for the competing risk of death. No significant difference in the risk of bladder cancer emerged between the SCI and control groups. Further analyses found a higher spinal level of SCI tended to predict a lower risk for prostate cancer. Patients with SCI incurred a lower risk for prostate cancer compared with people without SCI. The risk for bladder cancer did not differ between people with or without SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

Prostate cancer

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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)

Prediction of prostate cancer in unscreened men: external validation of a risk calculator.

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van Vugt, Heidi A; Roobol, Monique J; Kranse, Ries; Määttänen, Liisa; Finne, Patrik; Hugosson, Jonas; Bangma, Chris H; Schröder, Fritz H; Steyerberg, Ewout W

2011-04-01

Prediction models need external validation to assess their value beyond the setting where the model was derived from. To assess the external validity of the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator (www.prostatecancer-riskcalculator.com) for the probability of having a positive prostate biopsy (P(posb)). The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and validated in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively. P(posb) was calculated using serum prostate specific antigen (PSA), outcome of digital rectal examination (DRE), transrectal ultrasound and ultrasound assessed prostate volume. The external validity was assessed for the presence of cancer at biopsy by calibration (agreement between observed and predicted outcomes), discrimination (separation of those with and without cancer), and decision curves (for clinical usefulness). Prostate cancer was detected in 469 men (26%) of the Finnish cohort and in 124 men (23%) of the Swedish cohort. Systematic miscalibration was present in both cohorts (mean predicted probability 34% versus 26% observed, and 29% versus 23% observed, both pscreened men, but overestimated the risk of a positive biopsy. Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting. Copyright © 2010 Elsevier Ltd. All rights reserved.

Prostate specific cancer volume: a significant prognostic factor in prostate cancer patients at intermediate risk of failing radiotherapy

International Nuclear Information System (INIS)

Lankford, S.P.; Pollack, A.; Zagars, G.K.

1996-01-01

Purpose: Although the pretreatment serum prostate specific antigen level (PSAL) is the single most significant predictor of local and biochemical control in prostate cancer patients treated with radiotherapy, it is relatively insensitive for patients with a PSAL in the intermediate range (4-20 ng/ml). PSA density (PSAD) has been shown to be slightly more predictive of outcome than PSAL for this intermediate risk group; however, this improvement is small and of little use clinically. PSA cancer volume (PSACV) is an estimate of cancer volume based on PSA that was recently described by D'Amico and Propert (IJROBP 32:232, 1995) as providing significant and independent prognostic information in addition to PSAL. We report here a detailed comparison between this new prognostic factor, PSAL, and PSAD. Methods and Materials: The records of 356 patients treated with definitive external beam radiotherapy for regionally localized (T1-4, Nx, M0) adenocarcinoma of the prostate were reviewed. Each patient had a PSAL, biopsy Gleason score, and pretreatment prostate volume by transrectal ultrasonography. The median PSAL was 9.3 ng/ml and 66% had Gleason scores in the 2-6 range. The median radiation dose was 66.0 Gy and the median follow-up for those living was 27 months. PSACV is a calculated parameter that takes into account PSAL (total PSA), ultrasonographic prostate volume (estimate of PSA from benign epithelium), and Gleason grade (estimate of PSA per tumor volume). The median PSACV was 1.43 cc. Biochemical failure was defined as increases in two consecutive follow-up PSA levels, one increase by a factor > 1.5, or an absolute increase of > 1 ng/ml. Local failure was defined as a cancer-positive prostate biopsy, usually undertaken because of evidence of biochemical failure. Results: The distributions of PSACV and PSAL were similar and, when normalized by log-transformation, were highly correlated (p 4 cc, as compared to those with a PSACV ≤ 0.5 cc, was over 30%. Conclusion

Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

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Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2017-06-01

Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors

Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis.

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Boyle, Peter; Koechlin, Alice; Bota, Maria; d'Onofrio, Alberto; Zaridze, David G; Perrin, Paul; Fitzpatrick, John; Burnett, Arthur L; Boniol, Mathieu

2016-11-01

To review and quantify the association between endogenous and exogenous testosterone and prostate-specific antigen (PSA) and prostate cancer. Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective cohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo-controlled randomized trials of testosterone replacement therapy (TRT) that reported data on PSA and/or prostate cancer cases were retained. Meta-analyses were performed using random-effects models, with tests for publication bias and heterogeneity. Twenty estimates were included in a meta-analysis, which produced a summary relative risk (SRR) of prostate cancer for an increase of 5 nmol/L of testosterone of 0.99 (95% confidence interval [CI] 0.96, 1.02) without heterogeneity (I² = 0%). Based on 26 trials, the overall difference in PSA levels after onset of use of TRT was 0.10 ng/mL (-0.28, 0.48). Results were similar when conducting heterogeneity analyses by mode of administration, region, age at baseline, baseline testosterone, trial duration, type of patients and type of TRT. The SRR of prostate cancer as an adverse effect from 11 TRT trials was 0.87 (95% CI 0.30; 2.50). Results were consistent across studies. Prostate cancer appears to be unrelated to endogenous testosterone levels. TRT for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development. The current data are reassuring, although some caution is essential until multiple studies with longer follow-up are available. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

The influence of obesity in patients with prostate cancer - Review of the literature

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Maximilien C. Goris Gbenou

2013-04-01

Full Text Available ABSTRACTRecent studies have demonstrated an association between higher body mass index and increased aggressiveness in prostate cancer.The present narrative review, based on a search of Medline® and Embase® databases from October 1982 to October 2012, explores the relationship between higher body mass index and localized prostate cancer. In particular, the current epidemiological and mechanistic evidence for interactions between obesity and prostate cancer are discussed.Obesity is associated with alterations in androgen levels, decreased sex hormone binding globulin and increased estrogen levels, insulin resistance, hyperglycemia, alterations in plasma lipoprotein levels particularly raised triglycerides and reduced high density lipoprotein, decreased levels of adiponectin, and increased levels of circulating insulin-growth factor- 1, leptin and dietary saturated fats. Obese men have more aggressive prostate cancer with a greater percentage prostate involvement, increased tumor volume and higher-grade disease, enlarged prostates, high prostate-specific antigen levels, increased risk of having positive margins and recurrence.Moreover, there is strong evidence of the beneficial effects of functional foods for the treatment of obesity. Additionally, an increasing number of studies support that obesity-induced inflammation plays an important role in the development of obesity-related pathologies. Despite, the beneficial role of nutriment in prostate cancer control, the use of functional foods in prostate cancer is not recommended for lack of large epidemiological studies.This data supports the hypothesis that obese men have more aggressive prostate cancers and that the obesity is a modifiable risk factor of prostate cancer.Key Words: prostate cancer, metabolic syndrome, obesity, high BMI, risk factor, diet, functional foods.

Prostate Cancer Ambassadors

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Vines, Anissa I.; Hunter, Jaimie C.; Carlisle, Veronica A.; Richmond, Alan N.

2016-01-01

African American men bear a higher burden of prostate cancer than Caucasian men, but knowledge about how to make an informed decision about prostate cancer screening is limited. A lay health advisor model was used to train “Prostate Cancer Ambassadors” on prostate cancer risk and symptoms, how to make an informed decision for prostate-specific antigen screening, and how to deliver the information to members of their community. Training consisted of two, 6-hour interactive sessions and was implemented in three predominantly African American communities over an 8-month period between 2013 and 2014. Following training, Ambassadors committed to contacting at least 10 people within 3 months using a toolkit composed of wallet-sized informational cards for distribution, a slide presentation, and a flip chart. Thirty-two Ambassadors were trained, with more than half being females (59%) and half reporting a family history of prostate cancer. Prostate cancer knowledge improved significantly among Ambassadors (p ≤ .0001). Self-efficacy improved significantly for performing outreach tasks (p < .0001), and among women in helping a loved one with making an informed decision (p = .005). There was also an improvement in collective efficacy in team members (p = .0003). Twenty-nine of the Ambassadors fulfilled their commitment to reach at least 10 people (average number of contacts per Ambassador was 11). In total, 355 individuals were reached with the prostate cancer information. The Ambassador training program proved successful in training Ambassadors to reach communities about prostate cancer and how to make an informed decision about screening. PMID:27099348

Diet, body size, physical activity and risk of prostate cancer: An umbrella review of the evidence.

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Markozannes, Georgios; Tzoulaki, Ioanna; Karli, Dimitra; Evangelou, Evangelos; Ntzani, Evangelia; Gunter, Marc J; Norat, Teresa; Ioannidis, John P; Tsilidis, Konstantinos K

2016-12-01

The existing literature on the relationship between diet, body size, physical activity and prostate cancer risk was summarised by the World Cancer Research Fund Continuous Update Project (CUP). An evaluation of the robustness of this evidence is required to help inform public health policy. The robustness of this evidence was evaluated using several criteria addressing evidence strength and validity, including the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, number of prostate cancer cases, between-study heterogeneity, 95% prediction intervals, small-study effects bias, excess significance bias and sensitivity analyses with credibility ceilings. A total of 248 meta-analyses were extracted from the CUP, which studied associations of 23 foods, 31 nutrients, eight indices of body size and three indices of physical activity with risk of total prostate cancer development, mortality or cancer development by stage and grade. Of the 176 meta-analyses using a continuous scale to measure the exposures, no association presented strong evidence by satisfying all the aforementioned criteria. Only the association of height with total prostate cancer incidence and mortality presented highly suggestive evidence with a 4% higher risk per 5 cm greater height (95% confidence interval, 1.03, 1.05). Associations for body mass index, weight, height, dietary calcium and spirits intake were supported by suggestive evidence. Overall, the association of diet, body size, physical activity and prostate cancer has been extensively studied, but no association was graded with strong evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

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Hauswald, Henrik; Kamrava, Mitchell R.; Fallon, Julia M.; Wang, Pin-Chieh; Park, Sang-June; Van, Thanh; Borja, Lalaine; Steinberg, Michael L.; Demanes, D. Jeffrey, E-mail: JDemanes@mednet.ucla.edu

2016-03-15

Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

Blood fatty acid patterns are associated with prostate cancer risk in a prospective nested case-control study.

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Yang, Meng; Ayuningtyas, Azalea; Kenfield, Stacey A; Sesso, Howard D; Campos, Hannia; Ma, Jing; Stampfer, Meir J; Chavarro, Jorge E

2016-09-01

Circulating fatty acids are highly correlated with each other, and analyzing fatty acid patterns could better capture their interactions and their relation to prostate cancer. We aimed to assess the associations between data-derived blood fatty acid patterns and prostate cancer risk. We conducted a nested case-control study in the Physicians' Health Study. Fatty acids levels were measured in whole blood samples of 476 cases and their matched controls by age and smoking status. Fatty acid patterns were identified using principal component analysis. Conditional logistic regression was used to estimate odds ratio (OR) and 95 % confidence interval (CI). Two patterns explaining 40.9 % of total variation in blood fatty acid levels were identified. Pattern 1, which mainly reflects polyunsaturated fatty acid metabolism, was suggestively positively related to prostate cancer risk (ORquintile 5 vs. quintile 1 = 1.37, 95 % CI = 0.91-2.05, P trend = 0.07). Pattern 2, which largely reflects de novo lipogenesis, was significantly associated with higher prostate cancer risk (ORquintile5 vs. quintile1 = 1.63, 95 % CI = 1.04-2.55, P trend = 0.02). This association was similar across tumor stage, grade, clinical aggressiveness categories and follow-up time. The two patterns of fatty acids we identified were consistent with known interactions between fatty acid intake and metabolism. A pattern suggestive of higher activity in the de novo lipogenesis pathway was related to higher risk of prostate cancer.

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

Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC.

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Daniele Campa

2011-02-01

Full Text Available The mTOR (mammalian target of rapamycin signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC. We chose the SNPs (n = 11 with the strongest association with risk (p<0.01 and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele = 0.85, 95% CI 0.78-0.94, p = 1.3 x 10⁻³ for rs546950 and OR(allele = 0.84, 95% CI 0.76-0.93, p = 5.6 x 10⁻⁴ for rs4955720. We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.

Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer.

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Tseng, Yolanda D; Paciorek, Alan T; Martin, Neil E; D'Amico, Anthony V; Cooperberg, Matthew R; Nguyen, Paul L

2014-03-15

In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. From 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type. In total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer. © 2013 American Cancer Society.

Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.

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Gu, Fangyi; Zhang, Han; Hyland, Paula L; Berndt, Sonja; Gapstur, Susan M; Wheeler, William; Ellipse Consortium, The; Amos, Christopher I; Bezieau, Stephane; Bickeböller, Heike; Brenner, Hermann; Brennan, Paul; Chang-Claude, Jenny; Conti, David V; Doherty, Jennifer Anne; Gruber, Stephen B; Harrison, Tabitha A; Hayes, Richard B; Hoffmeister, Michael; Houlston, Richard S; Hung, Rayjean J; Jenkins, Mark A; Kraft, Peter; Lawrenson, Kate; McKay, James; Markt, Sarah; Mucci, Lorelei; Phelan, Catherine M; Qu, Conghui; Risch, Angela; Rossing, Mary Anne; Wichmann, H-Erich; Shi, Jianxin; Schernhammer, Eva; Yu, Kai; Landi, Maria Teresa; Caporaso, Neil E

2017-11-01

Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene-based and pathway-based analyses by applying the summary-based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (p pathway  circadian rhythm pathway in GAME-ON (p pathway  = 0.021); this association was not confirmed in GECCO (p pathway  = 0.76) or the combined data (p pathway  = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms. © 2017 UICC.

Prostate cancer staging with extracapsular extension risk scoring using multiparametric MRI

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Boesen, Lars; Chabanova, Elizaveta; Løgager, Vibeke

2015-01-01

OBJECTIVES: To evaluate the diagnostic performance of preoperative multiparametric MRI with extracapsular extension (ECE) risk-scoring in the assessment of prostate cancer tumour stage (T-stage) and prediction of ECE at final pathology. MATERIALS AND METHODS: Eighty-seven patients with clinically....../87 (36 %) patients. ECE risk-scoring showed an AUC of 0.65-0.86 on ROC-curve for both readers, with sensitivity and specificity of 81 % and 78 % at best cutoff level (reader A), respectively. When tumour characteristics were influenced by personal opinion, the sensitivity and specificity for prediction...... technique for preoperative prostate cancer staging • ECE risk scoring predicts extracapsular tumour extension at final pathology • ECE risk scoring shows an AUC of 0.86 on the ROC-curve • ECE risk scoring shows a moderate inter-reader agreement (K = 0.45) • Multiparametric MRI provides essential knowledge...