A Negative Confirmatory Biopsy Among Men on Active Surveillance for Prostate Cancer Does Not Protect Them from Histologic Grade Progression

Abstract Background Many men (21–52%) are reported to have no cancer on the second, also known as the confirmatory , biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased. Objective To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression. Design, setting, and participants Men were identified from our tertiary care center AS prostate cancer database (1995–2012). Eligibility criteria were prostate-specific antigen (PSA) ≤10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2. Intervention AS. Outcome measurements and statistical analysis Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model. Results and limitations Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5–61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively ( p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29–0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20–0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12–2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00–1.10; p = 0.04). Retrospective analysis was the major limitation of the study. Conclusions Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS.