Phase 3 clinical trial investigating the effect of selenium supplementation in men at high‐risk for prostate cancer

Phase 3 randomized, double-blind trial conducted at 20 sites in the United States and New Zealand. Participants were men at high risk for prostate cancer, defined by PSA >4 ng/ml and/or a suspicious digital rectal examination and/or PSA velocity >0.75 ng/ml/year, and all had a negative prostate biopsy at enrollment. The active selenium arms included 234 men in the 200 mg/day group and 233 men in the 400 mg/day group.

Men were assigned to oral high-selenium yeast at 200 mg/day or 400 mg/day, taken daily for up to 5 years and compared with placebo. The intervention was evaluated as selenium supplementation for prostate cancer chemoprevention.

Selenium did not reduce prostate cancer incidence or significantly affect PSA velocity versus placebo. For biopsy-proven prostate cancer, the hazard ratio was 0.94 [0.52, 1.7] with 200 mg/day and 0.90 [0.48, 1.7] with 400 mg/day; the overall cancer incidence comparison was not significant (P = 0.88). PSA velocity also was not significant for either dose (P = 0.18 and P = 0.17). Overall, the trial found no apparent role for selenium in prostate cancer chemoprevention in this high-risk population.

The active supplement arms were moderate in size, and the study packet provides limited information on attrition, dietary background, and prior supplement use. Participants were predominantly Caucasian men with a prior negative biopsy, which limits generalizability to other populations. No efficacy signal was seen despite long follow-up, and the results may not extend to different selenium formulations or risk groups.