Clinical-Bladder cancer The effect of sex on disease stage and survival after radical cystectomy: a population-based analysis Giuseppe Rosiello, M.D. a,b, *, Carlotta Palumbo, M.D. a,c , Angela Pecoraro, M.D. a,d , Stefano Luzzago, M.D. a,e , Marina Deuker, M.D. a,f , Lara Franziska Stolzenbach, M.D. a,g , Zhe Tian, M.Sc. a , Andrea Gallina, M.D. b , Giorgio Gandaglia, M.D. b , Francesco Montorsi, M.D. b , Shahrokh F. Shariat, M.D. h,i , Fred Saad, M.D. a , Alberto Briganti, M.D. b , Pierre I. Karakiewicz, M.D. a a Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada b Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy c ASST Spedali Civili of Brescia. Department of Medical and Surgical Specialties, Urology Unit, Radiological Science and Public Health, University of Bres- cia, Italy d Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Turin, Italy e Department of Urology, European Institute of Oncology, Milan, Italy f Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany g Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany h Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria i Institute of Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia Received 23 May 2020; received in revised form 16 August 2020; accepted 15 September 2020 Abstract 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 non- metastatic 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 inci- dence, 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 inter- vals [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. More- over, 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. Ó 2020 Elsevier Inc. All rights reserved. Keywords: Bladder cancer; Epidemiology; Non-organ-confined disease; SEER database; Survival *Corresponding author. Tel. +39 02.2643.7286 E-mail address: giusepperosiello@hotmail.it (G. Rosiello). https://doi.org/10.1016/j.urolonc.2020.09.004 1078-1439/Ó 2020 Elsevier Inc. All rights reserved. ARTICLE IN PRESS Urologic Oncology: Seminars and Original Investigations 000 (2020) 1-7