Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: results from the randomised, placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS).

BACKGROUND Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial. OBJECTIVE To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy. DESIGN, SETTING, AND PARTICIPANTS Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries. INTERVENTION The 5α-reductase inhibitor, dutasteride. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression. RESULTS AND LIMITATIONS Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p<0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35-76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p<0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53-75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study. CONCLUSIONS Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience. CLINICAL TRIAL REGISTRY ClinicalTrials.gov, NCT00558363.