Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene.

PURPOSE: Prostate cancer (PCa) prevention remains an appealing strategy for the reduction of overtreatment and secondary adverse effects. We evaluated the efficacy of toremifene citrate 20 mg in PCa prevention among men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy. PATIENTS AND METHODS: One thousand five hundred ninety men with HGPIN, or HGPIN and atypia, and no PCa on prostate biopsy were randomly assigned 1:1 to receive toremifene citrate 20 mg or placebo in a 3-year phase III, double-blind, multicenter trial. Men underwent annual biopsy until cancer detection or study end. Efficacy analysis was performed in 1,467 men who underwent at least one on-study biopsy. Baseline risk factors were evaluated to determine influence on cancer detection. RESULTS: Cancer was detected in 34.7% and 32.3% of men in the placebo and treatment groups, respectively, with no observed difference (P = .39, log-rank test) in PCa-free survival. The 3-year Kaplan-Meier PCa-free survival estimate was 54.9% (99% CI, 43.3% to 66.5%) in the placebo group and 59.5% (99% CI, 48.1% to 70.9%) in the treatment group. Exploration of baseline risk factors demonstrated no subset in which a risk reduction was observed. In the placebo group, 17.9%, 12.9%, and 13.6% of men at risk at the beginning of years 1, 2, and 3, respectively, were diagnosed with PCa. CONCLUSION: Although toremifene 20 mg did not lower the PCa detection rate, men with isolated HGPIN have a high likelihood of eventual PCa diagnosis, demonstrating they are ideal candidates for inclusion in chemoprevention trials and require surveillance by periodic prostate biopsy.