Anthony V. D’Amico

In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10-year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision-making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested.

PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

CONTEXT: Survival benefit in the management of high-grade clinically localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of androgen suppression therapy (AST), but long-term AST is associated with many adverse events. OBJECTIVE: To assess the survival benefit of 3-dimensional conformal radiation therapy (3D-CRT) alone or in combination with 6 months of AST in patients with clinically localized prostate cancer. DESIGN, SETTING, AND PATIENTS: A prospective randomized controlled trial of 206 patients with clinically localized prostate cancer who were randomized to receive 70 Gy 3D-CRT alone (n = 104) or in combination with 6 months of AST (n = 102) from December 1, 1995, to April 15, 2001. Eligible patients included those with a prostate-specific antigen (PSA) of at least 10 ng/mL, a Gleason score of at least 7, or radiographic evidence of extraprostatic disease. MAIN OUTCOME MEASURES: Time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits) and overall survival. RESULTS: After a median follow-up of 4.52 years, patients randomized to receive 3D-CRT plus AST had a significantly higher survival (P =.04), lower prostate cancer-specific mortality (P =.02), and higher survival free of salvage AST (P =.002). Kaplan-Meier estimates of 5-year survival rates were 88% (95% confidence interval [CI], 80%-95%) in the 3D-CRT plus AST group vs 78% (95% CI, 68%-88%) in the 3D-CRT group. Rates of survival free of salvage AST at 5 years were 82% (95% CI, 73%-90%) in the 3D-CRT plus AST group vs 57% (95% CI, 46%-69%) in the 3D-CRT group. CONCLUSION: The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinically localized prostate cancer.

CONTEXT: Comorbidities may increase the negative effects of specific anticancer treatments such as androgen suppression therapy (AST). OBJECTIVES: To compare 6 months of AST and radiation therapy (RT) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality. DESIGN, SETTING, AND PATIENTS: At academic and community-based medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men with localized but unfavorable-risk prostate cancer were randomized to receive RT alone or RT and AST combined. All-cause mortality estimates stratified by randomized treatment group and further stratified in a postrandomization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test. MAIN OUTCOME MEASURE: Time to all-cause mortality. RESULTS: As of January 15, 2007, with a median follow-up of 7.6 (range, 0.5-11.0) years, 74 deaths have occurred. A significant increase in the risk of all-cause mortality (44 vs 30 deaths; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9; P = .01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all-cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity (31 vs 11 deaths; HR, 4.2; 95% CI, 2.1-8.5; P < .001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all-cause mortality (13 vs 19 deaths; HR, 0.54; 95% CI, 0.27-1.10; P = .08). CONCLUSIONS: The addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable-risk prostate cancer. This result may pertain only to men without moderate or severe comorbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116220.