The effect of sex on disease stage and survival after radical cystectomy: a population-based analysis

Background: The increased awareness regarding the sex gap in bladder cancer (BCa) care over the last decade may have resulted in more timely-wise referral patterns and treatment of female patients with BCa. Thus, we tested the association of sex with disease stage at presentation, as well as with cancer-specific mortality (CSM) after radical cystectomy (RC) in a contemporary cohort of patients with nonmetastatic urothelial bladder cancer (UCUB). Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2016), we identified 14,086 patients (10,879 men and 3,207 women) treated with RC for non-metastatic UCUB. Temporal trend, interaction analyses, logistic regression, cumulative incidence, and competing-risks regression analyses were used. Results: Overall, 10,879 (77.2%) men and 3,207 (22.8%) women underwent RC between 2004 and 2016. Female gender was an independent predictor of non-organ-confined (NOC) UCUB at RC in multivariable analyses (odds ratio: 1.23; 95% confidence intervals [CI] 1.10–1.38; P < 0.001). While NOC rates in men decreased over time (from 54.8% to 45.7%; P < 0.01), NOC rates in women remained stationary (from 60.6% to 57.3%; P = 0.15) and the excess NOC rate between men and women increased from + 5.8% in 2004 to +11.6% in 2016. Moreover, in multivariable analyses adjusted for other covariates, female gender was an independent predictor of higher CSM after RC in NOC UCUB (HR: 1.14; 95%CI 1.04–1.24; P < 0.01), but not in localized UCUB (P = 0.06). Conclusion: It is worrisome that, while in men the rate of NOC is decreasing, NOC rates in females have not improved over time. Moreover, it is also worrisome that, despite adjustment for both pathological tumor and patient characteristics, female sex remains an adverse prognostic factor for CSM. Reassessment of referral, diagnostic, and treatment patterns aimed at eliminating these sex discrepancies appears warranted.