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Background: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of long-term PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT)., Methods: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race-stratified Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis., Results: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints., Conclusions: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT)., Methods: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time., Results: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores., Conclusion: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: To assess the impact of primary and secondary therapies for high- and intermediate-risk prostate cancer on health-related quality of life (HRQoL)., Materials and Methods: A prospective study was initiated in 2007 at Center for Prostate Disease Research Multicenter National Database sites. Longitudinal patterns in HRQoL from baseline (pre-treatment) to 5 years post-diagnosis were examined for patients with high- and intermediate-risk prostate cancer, treated by radical prostatectomy (RP) or external beam radiation therapy (EBRT). Change in HRQoL was modeled using linear regression models fit with generalized estimating equations. The probability of maintaining HRQoL was compared between patients receiving RP only versus RP with secondary treatment., Results: Of 445 men with high- and intermediate-risk prostate cancer, 228 underwent RP and 143 had EBRT± androgen deprivation therapy (ADT). Fifty received secondary therapy (EBRT and/or ADT or chemotherapy) after RP. RP patients showed a greater decline over time in sexual function and bother and urinary function compared to EBRT±ADT patients. Patients who had secondary therapy after RP were less likely to maintain their HRQoL compared to those who had RP alone. These differences were most pronounced for sexual and hormonal function., Conclusions: Prostate cancer patients experience significant declines in HRQoL after primary therapy. Additional secondary therapy after RP, in the form of EBRT and/or ADT, appears to be responsible for further deterioration in HRQoL outcomes.

Purpose: The aim of this study was to identify the effects of subsequent prostate needle biopsies after the baseline biopsy on health related quality of life with time. We compared men with and without prostate cancer, and men who did and did not undergo followup prostate needle biopsy., Materials and Methods: Included in analysis were patients enrolled in the Center for Prostate Disease Research Multicenter National Database between 2007 and 2015 who had low or favorable intermediate risk prostate cancer, were on active surveillance and underwent prostate needle biopsy for suspicion of prostate cancer. Patients completed the EPIC (Expanded Prostate Cancer Index Composite) and the RAND SF-36 (36-Item Short Form Health Survey) after baseline biopsy and at regular followup intervals. Mean health related quality of life was compared with time between patients who did and did not undergo subsequent prostate needle biopsies following baseline., Results: Of the 637 patients included in study 129 (20.3%) with prostate cancer were on active surveillance and 508 (79.7%) were in the noncancer group. In the cancer and noncancer groups mean ± SD followup was 34.7 ± 16.9 and 31.6 ± 14.6 months, respectively. Of the patients with prostate cancer 54 (60.7%) underwent subsequent prostate needle biopsies compared with 114 (27.1%) without cancer. No significant impact on health related quality of life was observed in men who underwent subsequent prostate needle biopsies during a 5-year period., Conclusions: A subsequent prostate needle biopsy is required in most active surveillance protocols and in men with persistent suspicion of prostate cancer. Our analysis shows that subsequent prostate needle biopsies do not significantly impact health related quality of life.

Introduction: Patients with low-risk prostate cancer (PCa) often have excellent oncologic outcomes. However, treatment with curative intent can lead to decrements in health-related quality of life (HRQoL). Patients treated with radical prostatectomy have been shown to suffer declines in urinary and sexual HRQoL as compared to those managed with active surveillance (AS). Similarly, patients treated with external-beam radiation therapy (EBRT) are hypothesized to experience greater declines in bowel HRQoL. As health-related quality-of-life (HRQoL) concerns are paramount when selecting among treatment options for low-risk PCa, this study examined HRQoL outcomes in men undergoing EBRT as compared to AS in a prospective, racially diverse cohort., Methods: A prospective study of HRQoL in patients with PCa enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database was initiated in 2007. The current study included patients diagnosed through April 2014. HRQoL was assessed with the Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Study Short Form (SF-36). Temporal changes in HRQoL were compared for patients with low-risk PCa managed on AS vs. EBRT at baseline, 1-, 2-, and 3 years post-PCa diagnosis. Longitudinal patterns were modeled using linear regression models fitted with generalized estimating equations (GEE), adjusting for baseline HRQoL, demographic, and clinical patient characteristics., Results: Of the 499 eligible patients with low-risk PCa, 103 (21%) selected AS and 60 (12%) were treated with EBRT. Demographic characteristics of the treatment groups were similar, though a greater proportion of patients in the EBRT group were African American (P = 0.0003). At baseline, both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year (adjusted mean score: 87 vs. 95, P = 0.001 and 89 vs. 95, P = 0.008, respectively) and 2 years (87 vs. 93, P = 0.007 and 87 vs. 96, P = 0.002, respectively) compared to patients managed on AS. In contrast to those on AS, more than half the number of patients who received EBRT experienced a decline in bowel function (52% vs. 17%, p=0.003) and bother (52% vs. 15%, P = 0.002) from baseline to 1 year. Patients who received EBRT were significantly more likely to experience a decrease in more than one functional domain (urinary, sexual, bowel, or hormonal) at 1 year when compared with those on AS (60% vs. 28%, P = 0.004)., Conclusions: Patients receiving EBRT for low-risk prostate cancer suffer declines in bowel HRQoL. These declines are not experienced by patients on AS, suggesting that management of low-risk prostate cancer with AS may offer a means for preserving HRQoL following prostate cancer diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer. However, the impact of active surveillance on health related quality of life compared to that in men without cancer remains unknown. In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy., Materials and Methods: A prospective study was conducted on men who were enrolled into the Center for Prostate Disease Research Multicenter National Database and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014. Health related quality of life was assessed at biopsy (baseline) and annually for up to 3 years using SF-36 and EPIC questionnaires. Health related quality of life scores were modeled using generalized estimating equations, adjusting for baseline health related quality of life, and demographic and clinical characteristics., Results: Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy (noncancer comparison group). Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance. Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time., Conclusions: In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer. A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To perform patient-specific meta-analysis (MA) of two independent clinical validation studies of a 17-gene biopsy-based genomic assay as a predictor of favorable pathology at radical prostatectomy., Materials and Methods: Patient-specific MA was performed on data from 2 studies (732 patients) using the Genomic Prostate Score (GPS; scale 0-100) together with Cancer of the Prostate Risk Assessment (CAPRA) score or National Comprehensive Cancer Network (NCCN) risk group as predictors of the likelihood of favorable pathology (LFP). Risk profile curves associating GPS with LFP by CAPRA score and NCCN risk group were generated. Decision curves and receiver operating characteristic curves were calculated using patient-specific MA risk estimates., Results: Patient-specific MA-generated risk profiles ensure more precise estimates of LFP with narrower confidence intervals than either study alone. GPS added significant predictive value to each clinical classifier. A model utilizing GPS and CAPRA provided the most risk discrimination. In decision-curve analysis, greater net benefit was shown when combining GPS with each clinical classifier compared with the classifier alone. The area under the receiver operating characteristic curve improved from 0.68 to 0.73 by adding GPS to CAPRA, and 0.64 to 0.70 by adding GPS to NCCN risk group. The proportion of patients with LFP >80% increased from 11% using NCCN risk group alone to 23% using GPS with NCCN. Using GPS with CAPRA identified the highest proportion-31%-of patients with LFP >80%., Conclusion: Patient-specific MA provides more precise risk estimates that reflect the complete body of evidence. GPS adds predictive value to 3 widely used clinical classifiers, and identifies a larger proportion of low-risk patients than identified by clinical risk group alone., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: For patients with low-risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa., Methods: Beginning in 2007, HRQoL data from validated questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND Medical Outcomes Study short-form survey) were collected by the Center for Prostate Disease Research in a multicenter national database. Patients aged ≤75 years who were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for 3 years. Mean scores were estimated using generalized estimating equations adjusting for baseline HRQoL, demographic characteristics, and clinical patient characteristics., Results: Of the patients with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis revealed that patients in the RP group had significantly worse sexual function, sexual bother, and urinary function at all time points compared with patients in the AS group. Differences in mental health between groups were below the threshold for clinical significance at 1 year., Conclusions: In this study, no differences in mental health outcomes were observed, but urinary and sexual HRQoL were worse for patients who underwent RP compared with those who underwent AS for up to 3 years. These data offer support for the management of low-risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant declines in mental health., (© 2015 American Cancer Society.)

Background: Biomarkers that are validated in independent cohorts are needed to improve risk assessment for prostate cancer (PCa)., Objective: A racially diverse cohort of men (20% African American [AA]) was used to evaluate the association of the clinically validated 17-gene Genomic Prostate Score (GPS) with recurrence after radical prostatectomy and adverse pathology (AP) at surgery., Design, Setting, and Participants: Biopsies from 431 men treated for National Comprehensive Cancer Network (NCCN) very low-, low-, or intermediate-risk PCa between 1990 and 2011 at two US military medical centers were tested to validate the association between GPS and biochemical recurrence (BCR) and to confirm the association with AP. Metastatic recurrence (MR) was also evaluated., Outcome Measurements and Statistical Analysis: Cox proportional hazards models were used for BCR and MR, and logistic regression was used for AP. Central pathology review was performed by one uropathologist. AP was defined as primary Gleason pattern 4 or any pattern 5 and/or pT3 disease., Results and Limitations: GPS results (scale: 0-100) were obtained in 402 cases (93%); 62 men (15%) experienced BCR, 5 developed metastases, and 163 had AP. Median follow-up was 5.2 yr. GPS predicted time to BCR in univariable analysis (hazard ratio per 20 GPS units [HR/20 units]: 2.9; p<0.001) and after adjusting for NCCN risk group (HR/20 units: 2.7; p<0.001). GPS also predicted time to metastases (HR/20 units: 3.8; p=0.032), although the event rate was low (n=5). GPS was strongly associated with AP (odds ratio per 20 GPS units: 3.3; p<0.001), adjusted for NCCN risk group. In AA and Caucasian men, the median GPS was 30.3 for both, the distributions of GPS results were similar, and GPS was similarly predictive of outcome., Conclusions: The association of GPS with near- and long-term clinical end points establishes the assay as a strong independent measure of PCa aggressiveness. Tumor aggressiveness, as measured by GPS, and outcomes were similar in AA and Caucasian men in this equal-access health care system., Patient Summary: Predicting outcomes in men with newly diagnosed prostate cancer is challenging. This study demonstrates that a new molecular test, the Genomic Prostate Score, which can be performed on a patient's original prostate needle biopsy, can predict the aggressiveness of the cancer and help men make decisions regarding the need for immediate treatment of their cancer., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: SEMA3B and SEMA3F are 2 closely related genes lying 80 kb apart on chromosome 3 that have been shown to suppress tumor formation in vivo and in vitro. Each gene has a single nucleotide polymorphism that results in a nonsynonymous coding change, rs2071203 (SEMA3B) and rs1046956 (SEMA3F), as well as noncoding single nucleotide polymorphisms., Materials and Methods: We performed a case-control study of 789 prostate cancer cases and 907 controls from 3 races/ethnicities to determine possible associations of 10 variants with prostate cancer risk or prognosis., Results: The risk of prostate cancer increased more than 2-fold in Hispanic men with TT alleles at rs2071203 in SEMA3B and with CC alleles for rs2072054 at the 5' end of SEMA3F (OR 2.13, 95% CI 1.12-4.04, p = 0.02 and OR 2.55, 95% CI 1.34-4.84, p = 0.0045, respectively). These 2 single nucleotide polymorphisms were also associated with a poor prognosis in Hispanic men (2.71 and 3.48-fold increased risk). A frequent G-C-G-G-A-T-C-C-T-G haplotype encompassing 10 SNPs was associated with an increased risk of prostate cancer and poor prognosis in Hispanic samples (OR 2.72, 95% CI 1.20-6.12, p = 0.016 and OR 3.32, 95% CI 1.21-9.10, p = 0.02). In nonHispanic white men the T-C-G-A-A-T-C-C haplotype was associated with a high Gleason score (OR 1.44, 95% CI 1.06-1.96, p = 0.021)., Conclusions: These data indicate that polymorphisms in SEMA3B and SEMA3F are associated with prostate cancer risk and poor prognosis in Hispanic and nonHispanic white men.

Purpose: Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors., Materials and Methods: This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test., Results: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001)., Conclusions: We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

Objectives: To test the accuracy of the 2001 Partin Tables in African American men who underwent radical prostatectomy at multiple centers throughout the United States., Methods: We compiled a large multiethnic cohort of men (n = 3748) treated with radical prostatectomy at multiple sites, including all of the sites of the Department of Veterans Affairs-based Shared Equal Access Regional Cancer Hospital (SEARCH) database (n = 1524), Wayne State University (n = 1305), the University of Texas Health Science Center (n = 522), and the Henry Ford Hospital (n = 397). We evaluated the accuracy of the 2001 Partin Tables using area under the receiver operator characteristic curve (AUC) separately among African American and white men., Results: African American men (n = 1188, 32%), despite being more likely to have clinical Stage T1c disease (56% versus 47%, chi-square P <0.001), had higher preoperative PSA values (9.1 versus 7.7 ng/mL, rank-sum P <0.001) and were more likely to have higher-grade disease on diagnostic biopsy (chi-square P = 0.005). Despite these differences in baseline clinical characteristics, the 2001 Partin Tables performed equally well in both racial groups. Specifically, there were no differences in the AUC for African American and white men for predicting organ-confined disease (AUC 0.73 versus 0.72; P = 0.56), extraprostatic extension (AUC 0.62 versus 0.62; P = 0.99), or seminal vesicle invasion (AUC 0.77 versus 0.79; P = 0.53)., Conclusions: These data lend further support to the idea that although baseline differences between the races existed that may underlie an overall more aggressive disease among African American men, for the individual patient, race is not valuable for prognostication.

Objectives: Family history has been identified as a risk factor for prostate cancer. We assessed the risk of prostate cancer in men with a positive family history (at least one first-degree or second-degree relative), normal digital rectal examination (DRE) and a serum prostate-specific antigen (PSA) level of 4.0 ng/mL., Methods: A total of 87 volunteers from the San Antonio Center of biomarkers of risk for prostate cancer study enrolled in a prospective study to assess the prevalence of prostate cancer in men with a family history of prostate cancer, normal DRE findings, and a serum PSA level of 4.0 ng/mL or less. All subjects underwent transrectal ultrasound-guided prostate biopsy., Results: Prostate cancer was diagnosed in 22 (25.3%) of the 87 participants. The PSA values were significantly greater statistically in the men with prostate cancer (median 2.1 ng/mL) than in the men without prostate cancer (median 1.2 ng/mL, P = 0.01), and the odds of prostate cancer nearly doubled for a doubling of the PSA level within this interval (odds ratio 1.97, P = 0.02). No statistically significant difference was found in age, race, or number and type of affected relatives in men with and without prostate cancer., Conclusions: The results of our study have demonstrated a high frequency of prostate cancer in men with a positive family history but normal DRE findings and a PSA level of 4.0 ng/mL or less. These prospectively collected data raise an important consideration regarding lowering the PSA cutoff values for offering biopsy in patients with a positive family history and normal DRE findings.

The number of men for whom testosterone is prescribed is rapidly increasing. The aging man normally demonstrates a gradual decline in testosterone. Symptoms of hypogonadism include erectile dysfunction, diminished libido, sarcopenia, increased adiposity, osteopenia and osteoporosis, impaired cognition, and depression. There is a paucity of data regarding both efficacy and safety of testosterone replacement therapy. Testosterone levels have been shown to modulate prostate cancer risk and progression. A prospective evaluation of prostate cancer risk with testosterone replacement therapy has not been conducted. We outline concerns and recommendations for the use of testosterone replacement therapy in the aging man.

Objectives: Provide a critical summary of the latest interpretation of findings from the Prostate Cancer Prevention Trial (PCPT)., Methods: Findings from PCPT and recently published post-hoc analyses are reviewed., Results: PCPT demonstrated that finasteride can reduce the prevalence of prostate cancer, permitted the first large-scale assessment of the performance characteristics of prostate-specific antigen for prostate cancer screening, and identified new-onset erectile dysfunction as an early predictor of cardiovascular events., Conclusions: PCPT has and will continue to yield valuable information regarding future strategies for prostate cancer prevention and detection, benign prostatic hyperplasia, and other matters of public health importance.

Purpose: We reviewed the results of preliminary studies of select novel agents for metastatic prostate cancer and discuss the potential benefit of these agents for earlier stage disease, eg biochemically recurrent prostate cancer with high risk features., Materials and Methods: Available data on select investigational immunotherapies as well as endothelin-A receptor antagonists and survivin inhibitors were obtained and reviewed through PubMed searches, conference proceedings and unpublished proprietary information, when available., Results: A large number of promising agents are in varying stages of development. Phase III results have been reported for the endothelin-A receptor antagonist atrasentan. Several immunotherapies are currently in phase II/III trials, namely the GM-CSF transduced tumor cell vaccine GVAX, the prostatic acid phosphatase loaded dendritic cell vaccine Provenge and the prostate specific antigen expressing poxvirus vaccine PROSTVAC-VF. Another immunotherapy, the prostate specific membrane antigen immunoconjugate MLN2704 (Millennium Pharmaceuticals, Cambridge, Massachusetts), is in phase I/II study. The first clinical inhibitors of survivin are in early phase I studies. Several of these agents, including atrasentan, have shown statistically significant but modest effects in the advanced disease setting in which they have been studied., Conclusions: Clinical trial design with these novel therapies presents particular challenges since most of these agents may induce disease stabilization rather than disease regression. There is a risk of false-negative results and failure to recognize a potentially efficacious agent if these cytostatic agents are studied only in men with advanced, heavily pretreated disease in whom life expectancy is measured in months. We advocate the early referral and enrollment of men with high risk prostate cancer in clinical trials.

Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.

Prostate cancer is a significant cause of disease and death, making it an attractive target for chemoprevention. The association between lifetime exposure to dihydrotestosterone and risk of developing prostate cancer suggests that chemoprevention is possible with 5alpha-reductase inhibition. The recently completed Prostate Cancer Prevention Trial indicates that chemoprevention is possible with the 5alpha-reductase inhibitor finasteride. Development of a cost-effective chemoprevention strategy for prostate cancer is evolving, and is expected to have significant positive economic and public health benefits.

Prostate cancer is the most common malignancy in men and, as a result, there has been a nationwide emphasis on screening and detection. With the widespread use of the prostate-specific antigen (PSA), prostate cancer screening effectively detects localized prostate cancer. However, recent reports have identified a significant proportion of prostate cancer in men with low PSA levels. Many of these cancers are higher-grade malignancies. Consequently, PSA may function more effectively as a screening tool when applied over a continuum that is associated with degree of risk, rather than a binary measure. Other markers are currently being investigated. Ideally, a marker will identify the malignancy that is a clinical threat, thereby avoiding intervention for indolent disease. Prevention strategies may be employed for higher-risk patients, and these strategies eventually may be tailored to genetic or other risks.