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).
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.
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).
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.
World journal of urology. 2021 Mar 13 [Epub ahead of print]
David D'Andrea, Francesco Soria, Anne J Grotenhuis, Eugene K Cha, Nuria Malats, Savino Di Stasi, Steven Joniau, Tommaso Cai, Bas W G van Rhijn, Jaques Irani, Jeffrey Karnes, John Varkarakis, Jack Baniel, Joan Palou, Marek Babjuk, Martin Spahn, Peter Ardelt, Renzo Colombo, Vincenzo Serretta, Guido Dalbagni, Paolo Gontero, Riccardo Bartoletti, Stephane Larré, Per-Uno Malmstrom, Richard Sylvester, Shahrokh F Shariat
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. ., Division of Urology, University of the Studies of Turin, AOU Città Della Salute e Della Scienza di Torino, Presidio Molinette, Turin, Italy., Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Department of Urology, Weill Medical College of Cornell, University, New York, NY, USA., Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Department of Urology, Policlinico Tor Vergata-University of Rome, Rome, Italy., Oncologic and Reconstructive Urology, Department of Urology, University Hospitals Leuven, Leuven, Belgium., Department of Urology, Santa Chiara Hospital, Trento, Italy., Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Urology, Centre Hospitalier Universitaire La Milétrie, University of Poitiers, Poitiers, France., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Sismanoglio Hospital, University of Athens, Athens, Greece., Department of Urology, Rabin Medical Centre, Tel Aviv, Israel., Department of Urology, Fundacio Puigvert, University of Barcelona, Barcelona, Spain., Department of Urology, Motol Hospital, University of Praha, Prague, Czech Republic., Department of Urology, University Hospital of Wuerzburg, Wuertzburg, Germany., Department of Urology, Universitätsklinik Freiburg, Freiburg, Germany., 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 Urology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Translational Research and New Technologies, University of Pisa, Pisa, Italy., Department of Urology, CHU de Reims, Reims, France., Department of Urology, Academic Hospital, Uppsala University, Uppsala, Sweden., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Brussels, Belgium., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.