Does neoadjuvant chemotherapy diminish the sex disparity in bladder cancer survival after radical cystectomy?

Introduction: Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database.
Methods: The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis.
Results: A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC.
Conclusions: In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes.
Competing Interests: Declaration of Competing Interest None
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