Prognostic impact of variant histologies in urothelial bladder cancer treated by radical cystectomy.

To evaluate variant histologies (VHs) for Disease-specific Survival (DSS) in patients with invasive urothelial bladder cancer (BC) undergoing radical cystectomy (RC).

We analyzed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BC at eight centers. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS across overall-cohort and three stage-based analyses. These were defined as "organ-confined" (≤pT2N0), "locally-advanced" (pT3-4N0), and "node-positive" (pTanyN1-3).

Overall, 784(72.5%) were pure urothelial carcinomas (UC), while the remaining 298(27.5%) harbored a VH. Squamous differentiation was the most common VH with 166(15.3%) cases followed by 40(3.7%) micropapillary, 29(2.7%) sarcomatoid, 18(1.7%) glandular, 14(1.3%) lymphoepithelioma-like, 13(1.2%) small-cell, 8(0.7%) clear-cell, 7(0.6%) nested and 3(0.3%) plasmacytoid cases. Median follow-up was 2.3 years. Overall, 534(49.4%) disease-related deaths occurred. In uni- and multivariable analysis, plasmacytoid and small-cell VHs were associated with worse DSS in the overall-cohort analysis (both, p=0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favorable DSS compared to pure UC. Clear-cell (p=0.015) and small-cell (p=0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively.

More than 25% of patients harbored a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathologic diagnosis of VHs may ensure a tailored counselling to identify patients who require more intensive management.

BJU international. 2023 Feb 06 [Epub ahead of print]

Francesco Claps, Maaike W van de Kamp, Roman Mayr, Peter J Bostrom, Shahrokh F Shariat, Katrin Hippe, Simone Bertz, Yann Neuzillet, Joyce Sanders, Wolfgang Otto, Michiel S van der Heijden, Michael A S Jewett, Robert Stöhr, Alexandre R Zlotta, Carlo Trombetta, Markus Eckstein, Laura S Mertens, Maximilian Burger, Yanish Soorojebally, Bernd Wullich, Riccardo Bartoletti, François Radvanyi, Nicola Pavan, Nanour Sirab, M Carmen Mir, Damien Pouessel, Theo H van der Kwast, Arndt Hartmann, Yair Lotan, Rossana Bussani, Yves Allory, Bas W G van Rhijn

Department of Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany., Department of Surgery (Urology) and Surgical Oncology, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada., Department of Urology, University of Texas Southwestern Medical center, Dallas, TX, USA., Department of Pathology, University Medical Center - Regensburg, Regensburg, Germany., Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany., Core Facility Molecular Pathology & Biobank, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Urological Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy., Institut Curie, CNRS, UMR144, Molecular Oncology team, PSL Research University, Paris, F-75005, France., Department of Urology & Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany., Unit of Urology, Department of Translational Research and New Technologies, University of Pisa, Pisa, Italy., Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain., Department of Pathology, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada., Department of Pathology, University of Trieste, Trieste, Italy.