5-alpha Reductase Inhibitor Use and Risk of Colorectal Cancer in Men with Benign Prostatic Hyperplasia: A Population-based Cohort Study

Background: 5-alpha reductase inhibitors (5ARi) are commonly prescribed for the treatment of benign prostatic hyperplasia (BPH) in men. Pre-clinical evidence suggests that 5ARi's may have a protective role in colorectal cancer initiation. However, no studies to date have investigated this association at the population level.

Objectives: This study aimed to investigate the risk of colorectal cancer associated with the use of 5ARi in a UK population.

Methods: We conducted a retrospective cohort study in the UK Clinical Practice Research Datalink using an active comparator new user design. From a base cohort of patients with incident BPH, we identified new users of 5ARi's and alpha blockers following a BPH diagnosis. After a 1-year exposure lag patients were followed up until a first ever diagnosis of colorectal cancer, death from any cause, end of registration with the general practice or 31st of December 2017. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of incident colorectal cancer associated with the use of 5ARi compared with alpha blockers, using an intention-to-treat approach. We repeated the primary analysis censoring on switch or add-on of the study drug and using inverse probability of treatment weights. Additional sensitivity analyses were performed to assess robustness of findings including varying time lag and using multiple imputation to account for missing data.

Results: 5,018 5ARi new users and 34,925 alpha blockers new users were identified for this study with an average follow-up of 6.61 years. Overall, the use of 5-alpha reductase inhibitors was not associated with the risk of colorectal cancer (HR: 1.11 95%CIs 0.88- 1.40). Analysis censoring on switching or adding on of study drugs and using inverse probability of treatment weights found similar results (HR: 1.09 95%CIs 0.81-1.45 and HR: 1.11 95%CIs 0.88-1.41, respectively). Findings from sensitivity analysis varying lag period and using multiple imputation were also consistent.

Conclusions: This was the first epidemiological investigation of 5ARis and colorectal cancer. Overall in this study, the use of 5ARi's in men with BPH was not associated with a reduced risk of colorectal cancer compared to men using alpha blockers.