Receipt of 5-Alpha Reductase Inhibitors Before Radical Cystectomy: Do They Render High-Grade Bladder Tumors Less Aggressive?

Purpose: To assess whether receipt of 5-alpha reductase inhibitors (5-ARIs) influences the findings on surgical pathology at the time of radical cystectomy (RC) and subsequent clinical outcomes. 5-ARIs may slow the progression of non-muscle-invasive bladder cancer.

Patients and methods: We retrospectively reviewed all patients who underwent RC at our institution between 2009 and 2017. Men were included who had urothelial cancer in the RC specimen. Patients with nonurothelial pathology or who had no cancer in the specimen were excluded. Odds ratios for pathologic features and hazard ratios for survival were adjusted for baseline patient characteristics and disease stage.

Results: Our study cohort included 338 men; 48 patients (14%) were receiving dutasteride or finasteride at time of RC, 58 (17%) metformin, and 195 (58%) statins. Among patients receiving 5-ARIs, there was a lower proportion of positive margins (P = .08) and lymphovascular invasion (P = .05). This was statistically significant when patients with urothelial carcinoma variants were excluded. Multivariable logistic regression analysis demonstrated that 5-ARI receipt was associated with a lower odds ratio (OR) for the presence of lymphovascular invasion (OR = 0.49; 95% confidence interval, 0.24-1.00; P = .049) and positive surgical margins (OR = 0.30; 95% confidence interval, 0.09-1.07; P = .063). Further, 5-ARI receipt was associated with better overall survival, with an adjusted hazard ratio of 0.40 (95% confidence interval, 0.19-0.83; P = .015). No similar tendencies were observed with metformin or statins.

Conclusion: 5-ARIs may exert a protective biologic effect on the invasive properties of high-grade urothelial carcinoma. Further research is needed to understand the therapeutic implications.