(136) Effect of Vaginal Estrogen on Incidence of Urinary Tract Infections in Women With Bladder Cancer: A Global Propensity-Matched Retrospective Cohort Study

Abstract Introduction Recurrent urinary tract infections (UTIs) pose a substantial burden for women with bladder cancer, complicating treatment and diminishing quality of life. Vaginal estrogen has been shown to reduce recurrent UTIs in postmenopausal women by improving epithelial integrity, restoring protective vaginal flora, and enhancing local antimicrobial defenses. However, its effectiveness in women with bladder cancer remains unknown. Objective This study evaluated whether vaginal estrogen use is associated with reduced UTI incidence and improved infection-free survival in this high-risk population using a large global federated real-world database. Methods We performed a retrospective cohort study using the TriNetX Research Network (2005-2025). Women with bladder cancer (ICD-10-CM codes C67.0-C67.9, D09.0, C79.11, Z85.51) were identified and categorized based on whether they had a documented prescription for vaginal estrogen after diagnosis versus no estrogen exposure. Propensity score matching (1:1) across demographics, comorbidities, and bladder cancer–related variables produced two well-balanced cohorts. Outcomes included UTI incidence, defined as UTI or urosepsis based on ICD-10-CM codes within one year of bladder cancer diagnosis and infection-free survival. Risk ratios (RR), hazard ratios (HR), and Kaplan–Meier analyses were used to compare groups. Results A total of 72 190 women with bladder cancer were identified, including 4715 vaginal estrogen users and 67 475 non-users. After propensity matching, 3161 women remained in each cohort with well-balanced baseline characteristics, including age (mean 68.6 ± 13.0 years), race, BMI, and comorbidities. Vaginal estrogen users demonstrated a lower risk of UTI compared with non-users (9.5% vs 11.5%; p = 0.05; RR 1.20, 95% CI 0.99–1.45). Kaplan–Meier analysis showed significantly higher infection-free survival among vaginal estrogen users (log-rank χ2 = 6.95, p = 0.008), with survival probabilities of 89.2% vs 86.4%. The estimated hazard ratio of infection-free survival was 1.31 (95% CI 1.07–1.59), indicating a 30% relative risk reduction. Conclusions Vaginal estrogen was associated with improved infection-free survival in women with bladder cancer, indicating a clinically meaningful reduction in UTI risk. Given the high burden of UTIs in this population, even modest absolute risk reductions are important, especially with a safe, low-cost, and easily implemented therapy. Future studies should assess whether the benefit extends to patients undergoing bladder-directed treatments such as BCG or intravesical chemotherapy. Key limitations include potential diagnostic coding inaccuracies and the inherent constraints of real-world database analyses. Disclosure No.