To evaluate whether baseline prostate atrophy (PA) extent is associated with prostate cancer (PCa) incidence at 2-year repeat prostate biopsy in a clinical trial with systematic biopsies.

We performed a retrospective analysis of 3,165 men 50-75 years-old with prostate-specific antigen (PSA) between 2.5-10ng/mL and a prior negative biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) trial who underwent a 2-year repeat biopsy. Prostate atrophy extent was defined as the percentage of cores with atrophic changes. The association of baseline PA with positive 2-year biopsies was evaluated with logistic regression in uni- and multivariable analysis, controlling for baseline covariates.

Prostate atrophy involving none, 1-25%, 26-50%, 51-75% and >75% of the baseline cores was observed in 966/3,165 (30.5%), 1189/3,165 (37.6%), 677/3,165 (21.4%), 209/3,165(6.6%), 124/3,165 (3.9%) cases, respectively. More extensive PA was associated with older age, lower prostate-specific antigen, larger prostate volume and higher prevalence of acute and chronic inflammations (all P<0.05). Compared to subjects without PA, those with 1-25%, 26-50%, 51-75% and >75% core involvement had an odds-ratio for PCa of 0.65 (95%CI=0.52-0.81), 0.60 (95%CI=0.46-0.78), 0.56 (95%CI=0.37-0.86) and 0.35 (95%CI=0.19-0.67), respectively. In multivariable analysis, the extent of PA was independently associated with lower PCa risk (P<0.001). More extensive PA was associated with lower incidence of low- (Gleason 2-6) and high-grade (Gleason 7-10) PCa.

The extent of baseline prostate atrophy is independently associated with lower PCa risk in a dose dependent fashion.