Phase III Trial of Selenium to Prevent Prostate Cancer in Men with High-grade Prostatic Intraepithelial Neoplasia: SWOG S9917

Phase III, multicenter, randomized, placebo-controlled prevention trial in men aged 40 years or older with biopsy-confirmed high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer. Participants were enrolled in the United States through SWOG sites and collaborating ECOG, CALGB, and MAVERIC VA centers.

Selenium was given orally as selenomethionine at 200 mg/d daily for 3 years or until prostate cancer diagnosis. The active regimen was compared with placebo in a randomized prevention trial.

Selenium did not reduce progression to prostate cancer in men with high-grade prostatic intraepithelial neoplasia. Three-year prostate cancer rates were 35.6% with selenium and 36.6% with placebo, with no significant difference after adjustment (P = 0.73) or unadjusted analysis (P = 0.86). In the endpoint-known subgroup, prostate cancer was diagnosed in 48 of 135 selenium participants and 49 of 134 placebo participants. A non-significant subgroup signal suggested possible benefit in the lowest baseline selenium quartile, but overall incidence, cancer aggressiveness, and end-of-study biopsy outcomes were similar between groups.

Follow-up was limited to 3 years, which may be too short for a prevention endpoint in this setting. Endpoint status was not available for all randomized participants, and the baseline selenium subgroup analyses were exploratory and underpowered. The trial was conducted in selenium-replete U.S. men with HGPIN, which limits generalizability to selenium-deficient populations.