Words of wisdom. Re: Effect of dutasteride on the risk of prostate cancer. Andriole G, Bostwick D, Brawley O, et al. N Engl J Med 2010;362:1192-202

Abstract

This is the first published report of the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial, a 4-yr, multicenter, randomized, double-blind, placebo-controlled study involving 6729 men and comparing dutasteride 0.5 mg daily to placebo. The study was similar to the Prostate Cancer Prevention Trial (PCPT) [1] with some key differences. To be eligible, men had to have a prostate-specific antigen (PSA) level between 2.5 and 10 ng/ml, and a prior negative prostate biopsy (6-12 cores) within 6 mo before enrollment (vs a PSA <3.0 in PCPT); and the biopsies were at 2 and 4 yr (vs 7 yr). The primary end point was the presence of cancer on 10-core biopsy at 2 and 4 yr. Eighty-three percent of participants were biopsied(vs < 50% in PCPT). Less than 7% of cancers were diagnosed on protocol-independent biopsies (vs 52% of cancers diagnosed on for-cause biopsies in PCPT). Of the 3305 men in the dutasteride group and the 3424 men in the placebo group, 659 (20%) and 858 (25%), respectively, had cancer on the follow-up biopsies-an absolute reduction of 5.1% and a relative risk reduction of 23% ( p < 0.001). There was no difference between the groups in Gleason 7-10 cancers overall. Twenty-nine patients on dutasteride had Gleason 8-10,compared with 19 on placebo ( p = 0.15). The most likely explanation for this difference was the removal of 141 more men from the trial with Gleason 5-7 cancers. Based on surveillance studies, about 7% would be upgraded to Gleason 8-10 on rebiopsy [2]. Dutasteride also decreased the rate of urinary retention (1.6% vs 6.7%: a 77.3% relative reduction).