5α-Reductase Inhibitors and Risk of Prostate Cancer Death.

Abstract

5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group. Prostate Cancer data Base Sweden consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Of 89,227 men diagnosed with prostate cancer between July 2007 and December 2016, 5,816 had been on 5α-reductase inhibitors for more than 180 days before the date of diagnosis. Followup ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio for prostate cancer death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high risk cancer were stratified according to Gleason Grade Group. In men with high risk cancer the risk of prostate cancer death was similar among 5α-reductase inhibitor users and nonusers, with Gleason Grade Group 1 HR 1.02 (95% CI 0.53-1.95), Gleason Grade Group 2 HR 1.04 (95% CI 0.65-1.69), Gleason Grade Group 3 HR 1.27 (95% CI 0.89-1.80), Gleason Grade Group 4 HR 0.95 (95% CI 0.76-1.18) and Gleason Grade Group 5 HR 0.99 (95% CI 0.83-1.19), for 5α-reductase inhibitor users vs nonusers. We found no evidence that 5α-reductase inhibitors affect Gleason grading as no difference in mortality was observed among 5α-reductase inhibitor users and nonusers in each Gleason group.