Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients

Objective: To test the expandability of active surveillance (AS) to Gleason score 3 + 4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort. Materials and methods: We performed a retrospective analysis including 2,323 patients with localized Gleason score 3 + 4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3 + 4). Results: The final pathologic Gleason score was 3 + 3 = 6 in 8%, 3 + 4 = 7 in 67%, 4 + 3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level > 10 ng/ml, PSA density (PSAD) > 0.15 ng/ml/g, clinical stage > T1, and >2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level <= 10 ng/ml, PSAD <= 0.15 ng/ml/g, T1c, and <= 2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers. Conclusions: Approximately half of patients with biopsy Gleason score 3 + 4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a <20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy and serum markers may be especially beneficial in this group of patients. (C) 2014 Elsevier Inc. All rights reserved.