OBJECTIVE: To evaluate the impact of discordant histological diagnoses between transurethral resection of bladder tumour (TURBT) and radical cystectomy (RC) on cancer-specific mortality (CSM) in patients with bladder cancer (BCa). PATIENTS AND METHODS: We relied on a multi-institutional database collecting data of patients with BCa who underwent TURBT and subsequent RC from nine centres between 2000 and 2023. We tested concordance rates between TURBT and RC in detecting urothelial carcinoma of the urinary bladder (UCUB) as well as non-UCUB hystological subtypes, using RC as the reference standard. Concordance was defined as the agreement between a specific histological subtype identified both at TURBT and RC and evaluated according to Cohen's kappa coefficient. Subsequently, survival analyses consisted of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressing CSM according to concordance between TURBT and RC (namely, concordant vs discordant). RESULTS: Overall, 3160 patients were identified. Of these, 2762 (87%) harboured UCUB and 398 (13%) non-UCUB at TURBT vs 2481 (79%) UCUB and 679 (21%) non-UCUB at RC. There were 683 (21.6%) patients with a discordant diagnosis between TURBT and RC. The overall concordance in detecting non-UCUB subtypes was defined as fair concordance (Cohen's kappa coefficient: 0.32). In MCR models, a discordant diagnosis exhibited higher CSM relative to those with a concordant diagnosis (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1-1.6; P = 0.002). In a sensitivity analysis including patients with UCUB not exposed to neoadjuvant chemotherapy, this survival disadvantage was even higher (HR 1.5, 95% CI 1.1-1.7; P = 0.04). CONCLUSIONS: A discordant histopathological diagnosis between TURBT and RC is associated with higher CSM rates, particularly in cases initially misdiagnosed as UCUB. However, we also observed a moderate concordance between TURBT and RC in identifying non-UCUB subtypes.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Centre Montréal Québec Canada

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

Department of Urology and Oncological Urology Wrocław Medical University Wrocław Poland

Department of Urology Azienda Ospedaliera Universitaria Integrata Verona Verona Italy

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

Department of Urology Fundacio Puigvert Barcelona Spain

Department of Urology IEO European Institute of Oncology IRCCS Milan Italy

Department of Urology Kantonsspital Aarau Aarau Switzerland

Department of Urology Luzerner Kantonsspital Lucerne Switzerland

Department of Urology Netherlands Cancer Institute Amsterdam The Netherlands

Department of Urology Onze Lieve Vrouwziekenhuis Hospital Aalst Belgium

Department of Urology Regina Elena _National Cancer Institute IRCCS Rome Italy

Department of Urology Spedali Civili of Brescia Brescia Italy

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology UROSUD La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology Weill Cornell Medical College New York NY USA

Division of Experimental Oncology Unit of Urology URI Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Division of Urology Department of Surgical Sciences San Giovanni Battista Hospital University of Studies of Torino Turin Italy

GRC 5 Predictive Onco Uro AP HP Urology Pitie Salpetriere Hospital Sorbonne University Paris France

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

ORSI Academy Ghent Belgium

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