Purpose To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active-surveillance program. Methods Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model. Results A total of 1,298 men (median age, 66 years) with a median follow-up of 5 years (range, 0.01 to 18.00 years) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range, 0.01 to 18 years). Factors associated with grade reclassification were older age (hazard ratio [HR], 1.03 for each additional year; 95% CI, 1.01 to 1.06), prostate-specific antigen density (HR, 1.21 per 0.1 unit increase; 95% CI, 1.12 to 1.46), and greater number of positive biopsy cores (HR, 1.47 for each additional positive core; 95% CI, 1.26 to 1.69). Factors associated with intervention were prostate-specific antigen density (HR, 1.38 per 0.1 unit increase; 95% CI, 1.22 to 1.56) and a greater number of positive biopsy cores (HR, 1.35 for one additional positive core; 95% CI, 1.19 to 1.53). Conclusion Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention.

Background: Mutations in DNA repair genes are associated with aggressive prostate cancer (PCa). Objective: To assess whether germline mutations are associated with grade reclassification (GR) in patients undergoing active surveillance (AS). Design, setting, and participants: Two independent cohorts of PCa patients undergoing AS; 882 and 329 patients from Johns Hopkins and North Shore, respectively. Outcome measurements and statistical analysis: Germline DNA was sequenced for DNA repair genes, including BRCA1/2 and ATM (three-gene panel). Pathogenicity of mutations was defined according to the American College of Medical Genetics guidelines. Association of mutation carrier status and GR was evaluated by a competing risk analysis. Results and limitations: Of 1211, 289 patients experienced GR; 11 of 26 with mutations in a three-gene panel and 278 of 1185 noncarriers; adjusted hazard ratio (HR) = 1.96 (95% confidence interval [CI] = 1.004–3.84, p = 0.04). Reclassification occurred in six of 11 carriers of BRCA2 mutations and 283 of 1200 noncarriers; adjusted HR = 2.74 (95% CI = 1.26–5.96, p = 0.01). The carrier rates of pathogenic mutations in the three-gene panel, and BRCA2 alone, were significantly higher in those reclassified (3.8% and 2.1%, respectively) than in those not reclassified (1.6% and 0.5%, respectively; p = 0.04 and 0.03, respectively). Carrier rates for BRCA2 were greater for those reclassified from Gleason score (GS) 3 + 3 at diagnosis to GS≥4 + 3 (4.1% vs 0.7%, p = 0.01) versus GS 3 + 4 (2.1% vs 0.6%; p = 0.03). Results are limited by the small number of mutation carriers and an intermediate end point. Conclusions: Mutation status of BRCA1/2 and ATM is associated with GR among men undergoing AS. Patient summary: Men on active surveillance with inherited mutations in BRCA1/2 and ATM are more likely to harbor aggressive prostate cancer.

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