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

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

doi:10.1111/bju.15984

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

BJU Int. 2023 Aug;132(2):170-180. doi: 10.1111/bju.15984. Epub 2023 Feb 20.

Authors

Francesco Claps^{1

2}, Maaike W van de Kamp¹, Roman Mayr³, Peter J Bostrom^{4

5}, Shahrokh F Shariat^{6

7

8

9}, Katrin Hippe¹⁰, Simone Bertz¹¹, Yann Neuzillet^{1

12

13}, Joyce Sanders¹², Wolfgang Otto³, Michiel S van der Heijden¹⁴, Michael A S Jewett⁴, Robert Stöhr¹¹, Alexandre R Zlotta⁴, Carlo Trombetta², Markus Eckstein¹¹, Laura S Mertens¹, Maximilian Burger³, Yanish Soorojebally¹³, Bernd Wullich¹⁵, Riccardo Bartoletti¹⁶, François Radvanyi¹³, Nicola Pavan², Nanour Sirab¹³, M Carmen Mir¹⁷, Damien Pouessel^{13

18}, Theo H van der Kwast¹⁹, Arndt Hartmann¹¹, Yair Lotan⁶, Rossana Bussani²⁰, Yves Allory^{13

21}, Bas W G van Rhijn^{1

3

4}

Affiliations

¹ Department of Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
² Urological Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
³ Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany.
⁴ Department of Surgery (Urology) and Surgical Oncology, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada.
⁵ Department of Urology, Turku University Hospital and University of Turku, Turku, Finland.
⁶ Department of Urology, University of Texas Southwestern Medical center, Dallas, TX, USA.
⁷ Department of Urology, Weill Cornell Medical College, New York, NY, USA.
⁸ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁹ Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁰ Department of Pathology, University Medical Center - Regensburg, Regensburg, Germany.
¹¹ Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany.
¹² Core Facility Molecular Pathology & Biobank, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹³ Institut Curie, CNRS, UMR144, Molecular Oncology Team, PSL Research University, Paris, France.
¹⁴ Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
¹⁵ Department of Urology & Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen/Nurnberg, Erlangen, Germany.
¹⁶ Unit of Urology, Department of Translational Research and New Technologies, University of Pisa, Pisa, Italy.
¹⁷ Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain.
¹⁸ Department of Medical Oncology, Claudius Regaud Institute, Toulouse University Cancer Center (IUCT) Oncopole, Toulouse, France.
¹⁹ Department of Pathology, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada.
²⁰ Department of Pathology, University of Trieste, Trieste, Italy.
²¹ Department of Pathology, Institut Curie, Paris, France.

PMID: 36748180
DOI: 10.1111/bju.15984

Abstract

Objectives: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC).

Materials and methods: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3).

Results: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable 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.

Conclusions: More than 25% of patients harboured 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 pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.

Keywords: #BladderCancer; #blcsm; #uroonc; #utuc; bladder urothelial carcinoma; prognosis; radical cystectomy; survival; variant histology.

MeSH terms

Carcinoma, Transitional Cell* / pathology
Cystectomy
Humans
Prognosis
Retrospective Studies
Urinary Bladder Neoplasms* / pathology