A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

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  • Aurélie Kamoun, Ligue Nationale Contre le Cancer
  • ,
  • Aurélien de Reyniès, Ligue Nationale Contre le Cancer
  • ,
  • Yves Allory, Institut Curie, PSL Research University
  • ,
  • Gottfrid Sjödahl, Lunds Universitet
  • ,
  • A. Gordon Robertson, BC Cancer Agency, Vancouver, British Columbia, Canada.
  • ,
  • Roland Seiler, University of Bern
  • ,
  • Katherine A. Hoadley, University of North Carolina at Chapel Hill
  • ,
  • Clarice S. Groeneveld, Universidade Federal do Parana, Ligue Nationale Contre le Cancer, CNRS
  • ,
  • Hikmat Al-Ahmadie, Memorial Sloan-Kettering Cancer Center
  • ,
  • Woonyoung Choi, Johns Hopkins University
  • ,
  • Mauro A.A. Castro, Universidade Federal do Parana
  • ,
  • Jacqueline Fontugne, Institut Curie, CNRS
  • ,
  • Pontus Eriksson, Lunds Universitet
  • ,
  • Qianxing Mo, Moffitt Cancer Center
  • ,
  • Jordan Kardos, University of North Carolina at Chapel Hill
  • ,
  • Alexandre Zlotta, University Toronto
  • ,
  • Arndt Hartmann, Lehrstuhl für Theoretische Chemie/Computer Chemie Centrum, Friedrich-Alexander Universität Erlangen-Nürnberg, Germany.
  • ,
  • Colin P. Dinney, University of Texas MD Anderson Cancer Center
  • ,
  • Joaquim Bellmunt, Harvard Medical School
  • ,
  • Thomas Powles, Queen Mary University of London
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  • Núria Malats, Spanish National Cancer Research Centre (CNIO)
  • ,
  • Keith S. Chan, Cedars-Sinai Medical Center
  • ,
  • William Y. Kim, University of North Carolina at Chapel Hill
  • ,
  • David J. McConkey, Johns Hopkins University
  • ,
  • Peter C. Black, The University of British Columbia
  • ,
  • Lars Dyrskjøt
  • Mattias Höglund, Lunds Universitet
  • ,
  • Seth P. Lerner, Baylor College of Medicine
  • ,
  • Francisco X. Real, Spanish National Cancer Research Centre (CNIO)
  • ,
  • François Radvanyi, CNRS
  • ,
  • The bladder Cancer Molecular Taxonomy Group

Background: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, and participants: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts. Outcome measurements and statistical analysis: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models. Results and limitations: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment. Conclusions: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials. Patient summary: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting. An international consortium of bladder cancer expert teams establishes a consensus reconciling the diverse molecular classifications of muscle-invasive bladder cancer. This work offers a robust framework that will enable testing and validating predictive biomarkers in future prospective clinical trials.

OriginalsprogEngelsk
TidsskriftEuropean Urology
Vol/bind77
Nummer4
Sider (fra-til)420-433
Antal sider14
ISSN0302-2838
DOI
StatusUdgivet - apr. 2020

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