Sex-related differences in non-urothelial variant histology, non-muscle invasive bladder cancer

Cent European J Urol. 2022;75(3):240-247. doi: 10.5173/ceju.2022.0053. Epub 2022 Jul 18.


Introduction: Non-urothelial variant histology (VH), non-muscle invasive bladder cancer (NMIBC) has received little attention in contemporary urologic literature. Specifically, the effect of female sex on stage at presentation, as well as on cancer-specific mortality (CSM) have not been previously examined in VH NMIBC. Our aim was to test the effect of female sex on stage at presentation and CSM in VH NMIBC.

Material and methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified patients aged ≥18 years, with histologically confirmed VH NMIBC. Logistic regression models addressed T1 stage at diagnosis after multivariable adjustments for tumor grade, age and race/ethnicity. Before Kaplan-Meier plots and Cox regression analyses, propensity score matched adjusting for histological variants, T-stage, tumor grade, age and race/ethnicity was performed.

Results: Overall, 2,205 VH NMIBC patients were identified. Of those, 28% (n = 607) were female. Females were older (77 vs 74 years, p <0.001) and more frequently harbored T1 stage (55 vs 45%, p <0.001). Female sex independently predicted T1 stage (odds ratio [OR] = 1.66, 95% Confidence Interval [CI] = 1.35-2.03, p <0.001). Female sex also exhibited higher CSM, after matching for all assessable variables, including stage (hazard ratio [HR] = 1.91, 95% CI = 1.45-2.54, p <0.001).

Conclusions: In VH NMIBC, female sex is an indicator of higher rate of T1 stage and, fully independently of stage, female sex also results in higher CSM.

Keywords: Epidemiology; Surveillance; adenocarcinoma; and End Results; neuroendocrine carcinoma; non-muscle invasive bladder cancer; squamous cell carcinoma; variant histology.