Background The incidence and mortality of renal cell carcinoma (RCC) exhibit marked sex-based differences, suggesting a potential role for androgen signaling in disease progression. Although 5α-reductase inhibitors (5-ARIs) are widely prescribed for benign prostatic conditions, their potential association with survival in patients with RCC remains poorly understood. We evaluated the association between long-term use of 5-ARIs and overall survival in men with RCC. Methods This population-based retrospective cohort study used data from the Korean National Health Insurance Service database (2007–2020). Men aged ≥40 years with newly diagnosed RCC were included. Long-term 5-ARI use was defined as cumulative prescription of finasteride or dutasteride for ≥365 days prior to diagnosis. Propensity score matching (1:3 ratio) was employed to balance baseline characteristics, including age, year of diagnosis, income, comorbidity burden, and hypertension. The primary outcome was all-cause mortality, analyzed using Cox proportional hazards regression models. Subgroup analyses were stratified by treatment modality and Charlson comorbidity index (CCI). Results Among 31,927 eligible men, 1,803 5-ARI users were matched with 5,409 non-users (mean age 71.2 years). Long-term 5-ARI use was associated with significantly lower all-cause mortality (hazard ratio HR: 0.88; 95% CI: 0.79–0.94; p 0.001). Although no significant associations were observed in patients undergoing surgery (HR: 0.94; 95% CI: 0.79–1.07) or systemic therapy (HR: 1.15; 95% CI: 0.82–1.55), a distinct survival benefit was evident in the no-surgery/no-systemic therapy group (HR: 0.82; 95% CI: 0.73–0.92; p 0.001). Within this untreated subgroup, the benefit was most pronounced in patients with low comorbidity (CCI 0–1: HR: 0.78; 95% CI: 0.65–0.91) compared with those with high comorbidity (CCI ≥2: HR: 0.89; 95% CI: 0.76–1.03). Conclusion Long-term 5-ARI use is associated with improved overall survival in men with RCC, particularly among those with low comorbidity who are managed without active oncological treatment. These findings suggest that androgen modulation may influence RCC progression and support the investigation of 5-ARIs as potential adjunctive agents in selected clinical settings.
Lee et al. (Fri,) studied this question.