5α-Reductase inhibitors (5ARI) reduced risk of prostate cancer (Pca) with 25% in two randomized trials but increased risk of Gleason 8-10 at biopsy. One explanation is that 5ARI induce morphological changes in Pca cells similar to higher Gleason grades but without its adverse biology. To assess this, we compared risk of Pca death between men on 5ARI and men not on 5ARI before Pca diagnosis, in each Gleason grade group (GGG).

Prostate Cancer data Base Sweden (PCBaSe) consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Out of 89 227 men diagnosed with Pca between July 2007 and December 2016, 5 816 men had been on 5ARI for more than 180 days before the date of diagnosis. Follow-up ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio (HR) for Pca death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high-risk cancer were stratified according to GGG.

In men with high-risk cancer, risk of Pca death was similar among 5ARI-users and non-users - GGG1: HR 1.02 (95% CI: 0.53-1.95), GGG2: HR 1.04 (95% CI: 0.65-1.69), GGG3: HR 1.27 (95% CI: 0.89-1.80), GGG4: HR 0.95 (95% CI: 0.76-1.18) and GGG5: HR 0.99 (95% CI: 0.83-1.19), for 5ARI users vs. non-users.

We found no evidence for that 5ARI affect Gleason grading since no difference in mortality was observed among 5ARI users and non-users in each Gleason group.