Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

Abstract

ImportanceThe antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored.ObjectiveTo assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression.Design, Setting, and ParticipantsThis cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023.ExposureNewly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled.Main Outcomes and MeasuresThe primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis.ResultsThe study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group.Conclusions and relevanceResults of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.

The Long-Term Impact of 5-alpha Reductase Inhibitors on the Development of Bladder Cancer and the Need for Radical Cystectomy: A Nationwide Observational Study

“…The biological characteristics of the tumor, including the stage and grade of BC, were not adjusted between groups in this study because of the lack of information from the currently available NHISS dataset. However, in that approximately 40% of subjects took a 5ARI, this study is similar to the prevention results of recently reported 1:1 matched studies, which showed a reduction in BC diagnoses in 93,197 [ 8 ] and 5,300 [ 18 ] men who initiated 5ARI treatment compared to men who did not start a 5ARI. Second, we did not investigate the clinical outcomes between different formulations of 5ARIs, including finasteride and dutasteride, currently available on the market.…”

“…While there was no significant difference in BC diagnosis within two years of 5ARI use (HR=1.05, 95% CI=0.82–1.32), the risk of BC diagnosis was significantly lower in the 5ARI group after 2 or more years of 5ARI use (HR=0.82, 95% CI=0.79–0.94) [ 10 ]. An et al [ 18 ] recently reported the outcome of a 1:1 propensity-matched study utilizing the nationwide cohort comparing 5,300 men diagnosed with BC. Compared with the control group, the 5ARI group had a lower risk of mortality (HR=0.83, 95% CI=0.75–0.91), bladder instillation (HR=0.84, 95% CI=0.77–0.92), and RC (HR=0.74, 95% CI=0.62–0.88).…”