The debate regarding 5-alpha reductase inhibitors (finasteride [Proscar] and dutasteride [Avodart]) and the risk of prostate cancer continues. Despite good evidence that the drugs reduce the overall risk of prostate cancer, there is also evidence that the drugs may increase the risk of high-grade prostate cancers (Gleason score 7-10). This was a finding of the Prostate Cancer Prevention Trial (PCPT) that was published in 2003. That finding was recently questioned in a study published in the British Medical Journal that found no risk of higher-grade prostate cancers (BMJ 2013;346:f3406, reported in the August Pharmacology Watch). Now, 10 years after the PCPT was originally published as an 8-year study, the 18-year follow-up has been published in the New England Journal of Medicine. Of the nearly 19,000 men who underwent randomization in the PCPT, prostate cancer was diagnosed in 10.5% of the finasteride group and 14.9% of the placebo group, a 30% reduction in the rate of prostate cancer (relative risk 0.70; 95% CI, 0.65-0.76; P < 0.001). But all of the reduction was in lower-grade prostate cancers. There was a slightly higher rate of high-grade cancer in the finasteride group (3.5% vs 3.0%, P = 0.05), but there was no difference in overall mortality. There was also no increase in mortality in men diagnosed with high-grade prostate cancer. The authors conclude that finasteride reduced the risk of prostate cancer by about one-third, and although high-grade cancer was more common in the finasteride group, there was no difference in overall mortality or survival after the diagnosis of prostate cancer (N Engl J Med2013;369:603-610). Dutasteride was also studied in the REDUCE trial and similarly found lower rates of low-grade prostate cancers but increased rates of higher-grade cancers (N Engl J Med 2010;362:1192-1202). Some have argued that the higher rate of high-grade cancers is due to higher surveillance and “detection bias,” but regardless of the cause, it is reassuring to know that there is no higher risk of mortality, at least in the PCPT. The FDA changed the labeling to both finasteride and dutasteride in 2011 regarding the increased risk of high-grade prostate cancers.