Introduction: Prostate cancer is the second most common diagnosis of cancer among men, and the fifth most common cause of cancer-specific death worldwide. There is currently mixed evidence on the effect of certain common medications on the risk of developing prostate cancer. The primary endpoint of this study was prostate biopsy outcome in association with three commonly prescribed pharmacological agents: of 5-alpha reductase inhibitors (5-ARIs), statins, and proton-pump inhibitors (PPIs). The secondary endpoint was diagnosis of clinically significant prostate cancer.

Methods: This retrospective cohort study used the Princess Margaret Cancer Centre prostate biopsy database to include men who underwent their first diagnostic prostate biopsy from January 2018 to December 2018. Exposure was defined as six months of taking any of 5-ARIs, statins, or PPIs for patients undergoing their first prostate biopsy. Prostate cancer was defined based on a pathology report, with Gleason score (GS) of ≥6 as the cutoff for prostate cancer diagnosis. Clinically significant prostate cancer was defined as GS of ≥7. Descriptive analyses for continuous variables, proportions for discrete variables, and comparative tests for continuous variables were used. Multivariate logistic regression with time-variable covariates was performed to control for confounders. 

Results: A total of 663 patients fulfilled the inclusion criteria. Cancer diagnosis was associated with increased likelihood of PPI use (19.8% vs. 11.4%, p=0.008) and statin use (36.7% vs. 23.7%, p<0.001), older age (mean 67.3±7.9 vs. 62.1±8.4), higher prostate-specific antigen (mean 28.6±190.6 vs. 6.1±3.9, p=0.016), and smaller prostate volume (mean 54.1±23.3 vs. 42.9±20.8, p<0.001). Compared to non-PPI users, the odds of cancer diagnosis among pantoprazole users was 2.45 (95% confidence interval [CI] 1.15–5.19, p=0.05). Pantoprazole use was also associated with 2.3 increased odds of clinically significant cancer diagnosis (95% CI 1.26–4.19, p=0.007). Statin use and 5-ARI use were not associated with increased risk of prostate cancer diagnosis.

Conclusions: Our results do indicate PPI use was associated with an increased risk of developing clinically significant prostate cancer. This data highlights a continued need to elicit a thorough medication history and actively monitor PPI use in men at risk for prostate cancer. Further larger. population-based cohort and randomized studies should provide more information in this important area.