Introduction: The ability of 5a-Reductase Inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. As such, our aim was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality.
Methods: We used routinely collected health care data from Ontario, Canada. Men =66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We also measured an additional five baseline variables which may have impacted the risk of future BC diagnosis: cystoscopy, cytology, Urine-dip, hematuria, and transurethral resection of bladder lesion. Only the first period of continuous use of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy (this lag period allowed time for a biologically plausible effect from the 5ARI to occur) and ended at the last date of 5ARI exposure + 1 year (to allow time for BC to be diagnosed, and due to the residual effects of 5ARIs).
Results: We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride). between 2003-2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (IQR 1.00, 4.27). Both BC diagnosis and BC mortality were significantly less common during the at-risk period among the 5ARI group (HR 0.76, 95%CI 0.70-0.83; and HR 0.66, 95%CI 0.53-0.82 respectively). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (HR 1.05 95%CI 0.82-1.32 during the period of 0- <2 years of 5ARI use; however after =2 years of 5ARI use the risk of BC diagnosis was significantly less among the 5ARI group (HR 0.82, 95%CI 0.79-0.94). In the adjusted model, BC mortality was lower among 5ARI users, but no longer significant (HR 0.82, 95%CI 0.65, 1.02).
Conclusions: In a large cohort of men using 5ARI, we demonstrated a decreased risk of BC diagnosis. This risk reduction was present after =2 years of continuous therapy.
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