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Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea
Min Ho An1,2, Min Seo Kim3, Chungsoo Kim4
1Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Importance:
The 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.
Objective:
To assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression.
Design, Setting, And Participants:
This 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.
Exposure:
Newly 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 Measures:
The 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.
Results:
The 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 Relevance:
Results of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.
Insights
This study found that 5-alpha-reductase inhibitors (5-ARIs) prescribed before a bladder cancer (BC) diagnosis were associated with a reduced risk of BC progression. The use of 5-ARIs, alongside alpha-blockers, lowered mortality and the need for invasive treatments.
Area of Science:
- Oncology
- Pharmacology
Background:
- 5-alpha-reductase inhibitors (5-ARIs) are known for their antiandrogenic effects, primarily studied in relation to prostate cancer prevention.
- Their role in urothelial bladder cancer (BC), another male-predominant cancer, remains less explored.
Purpose of the Study:
- To investigate the association between the prescription of 5-ARIs before a BC diagnosis and the subsequent risk of BC progression.
- To evaluate the impact of 5-ARI use on key clinical outcomes in male BC patients.
Main Methods:
- A nationwide cohort study utilizing Korean National Health Insurance Service claims data from 2008-2019.
- Propensity score matching was employed to compare outcomes between patients treated with alpha-blocker only versus 5-ARI plus alpha-blocker.
- Outcomes assessed included bladder instillation, radical cystectomy, and all-cause mortality using Cox regression and survival analysis.
Main Results:
- The 5-ARI plus alpha-blocker group (5300 patients) showed a significantly lower risk of all-cause mortality (aHR, 0.83), bladder instillation (HR, 0.84), and radical cystectomy (aHR, 0.74) compared to the alpha-blocker only group (5300 patients).
- Restricted mean survival time analysis indicated benefits in all-cause mortality (92.6 days), bladder instillation (88.1 days), and radical cystectomy (68.0 days) for the 5-ARI group.
- Incidence rates for bladder instillation and radical cystectomy were lower in the 5-ARI plus alpha-blocker group.
Conclusions:
- Prediagnostic prescription of 5-ARIs is associated with a reduced risk of bladder cancer progression.
- This finding suggests a potential therapeutic role for 5-ARIs in managing male urothelial bladder cancer, warranting further investigation.
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