PURPOSE: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). MATERIALS AND METHODS: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. RESULTS: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). CONCLUSION: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.

Departement of Urology Università Vita Salute Ospedale S Raffaele Milan Italy

Department of Surgical Oncological and Stomatological Sciences University of Palermo Palermo Italy

Department of Surgical Oncology Netherlands Cancer Institute Antoni Van Leeuwenhoek Hospital Amsterdam The Netherlands

Department of Translational Research and New Technologies University of Pisa Pisa Italy

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Academic Hospital Uppsala University Uppsala Sweden

Department of Urology Centre Hospitalier Universitaire La Milétrie University of Poitiers Poitiers France

Department of Urology CHU de Reims Reims France

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Fundacio Puigvert University of Barcelona Barcelona Spain

Department of Urology Mayo Clinic Rochester MN USA

Department of Urology Memorial Sloan Kettering Cancer Center New York NY USA

Department of Urology Motol Hospital University of Praha Prague Czech Republic

Department of Urology Policlinico Tor Vergata University of Rome Rome Italy

Department of Urology Rabin Medical Centre Tel Aviv Israel

Department of Urology Radboud University Nijmegen Medical Centre Nijmegen The Netherlands

Department of Urology Santa Chiara Hospital Trento Italy

Department of Urology Sismanoglio Hospital University of Athens Athens Greece

Department of Urology Universitätsklinik Freiburg Freiburg Germany

Department of Urology University Hospital of Wuerzburg Wuertzburg Germany

Department of Urology University of Jordan Amman Jordan

Department of Urology Weill Medical College of Cornell University New York NY USA

Division of Urology University of the Studies of Turin AOU Città Della Salute e Della Scienza di Torino Presidio Molinette Turin Italy

European Association of Urology Non Muscle Invasive Bladder Cancer Guidelines Panel Brussels Belgium

European Association of Urology Research Foundation Arnhem The Netherlands

Genetic and Molecular Epidemiology Group Spanish National Cancer Research Centre Madrid Spain

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Oncologic and Reconstructive Urology Department of Urology University Hospitals Leuven Leuven Belgium

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