Exploring the Impact of 5-Alpha Reductase Inhibitors on Bladder Cancer: Insights from a Large-Scale Prospective...

Emerging studies on the effect of 5-alpha reductase inhibitors (5ARIs) on bladder cancer (BC) risk yielded conflicting results. We aimed to explore the anti-tumor effect of 5ARIs on BC incidence, BC recurrence, BC risk of undergoing radical cystectomy, and BC-related mortality.

In this prospective cohort of 227,847 individuals from the UK biobank, we constructed the follow-up cohorts on 1 January 2011, with only the male population being included. The cohorts were followed up until 27 November 2023, when we conducted this study. Information on the medication of 5ARIs was recorded. The primary endpoints were the rate of BC incidence and BC-related mortality, while the secondary endpoints were the rate of BC local recurrence and BC risk of undergoing radical cystectomy. A strict and comprehensive sensitivity analysis was performed.

A total of 227,847 individuals without BC diagnosis at baseline were included for analysis. During a median follow-up of 12.9 years, there were 2487 new-onset BC events. 5ARI medication did not lower the risk of BC incidence significantly (hazard ratio 0.72, 95% confidence interval [CI] 0.43-1.18). When cumulative 5ARI medication duration exceeded 3 years, 5ARI medication only had a slight influence on BC incidence (life expectancy difference [LED] 12.04 days, 95% CI 2.54-21.54 for 3 years; LED 10.00 days, 95% CI 3.61-16.39 for 5 years). However, 5ARI medication predicted a higher risk of BC-related mortality (LED -867.84 days, 95% CI -1637.15 to -98.52) and BC risk of undergoing radical cystectomy (LED -955.83 days, 95% CI -1796.89 to -114.76) during a more than 10-year follow-up duration.

We did not find a strong protective role of 5ARIs in reducing the risk of BC incidence, BC-related mortality, BC local recurrence, and BC risk of undergoing radical cystectomy. A randomized controlled trial is warranted in the future.