A Consensus Molecular Classification of Muscle-invasive Bladder Cancer.

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.

To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes.

We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts.

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.

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.

This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials.

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.

European urology. 2019 Sep 25 [Epub ahead of print]

Aurélie Kamoun, Aurélien de Reyniès, Yves Allory, Gottfrid Sjödahl, A Gordon Robertson, Roland Seiler, Katherine A Hoadley, Clarice S Groeneveld, Hikmat Al-Ahmadie, Woonyoung Choi, Mauro A A Castro, Jacqueline Fontugne, Pontus Eriksson, Qianxing Mo, Jordan Kardos, Alexandre Zlotta, Arndt Hartmann, Colin P Dinney, Joaquim Bellmunt, Thomas Powles, Núria Malats, Keith S Chan, William Y Kim, David J McConkey, Peter C Black, Lars Dyrskjøt, Mattias Höglund, Seth P Lerner, Francisco X Real, François Radvanyi, Bladder Cancer Molecular Taxonomy Group

Cartes d'Identité des Tumeurs (CIT) Program, Ligue Nationale Contre le Cancer, Paris, France. Electronic address: ., Cartes d'Identité des Tumeurs (CIT) Program, Ligue Nationale Contre le Cancer, Paris, France., Department of Pathology, Institut Curie, Saint-Cloud, France; Institut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, Paris, France., Division of Urological Research, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden., Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC, Canada., Department of Urology, Bern University Hospital, Bern, Switzerland., Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Cartes d'Identité des Tumeurs (CIT) Program, Ligue Nationale Contre le Cancer, Paris, France; Institut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, Paris, France; Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Polytechnic Center, Curitiba, Brazil., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Johns Hopkins Greenberg Bladder Cancer Institute and Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA., Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Polytechnic Center, Curitiba, Brazil., Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden., Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Division of Urology, Department of Surgery, University of Toronto, Mount Sinai Hospital and University Health Network, Toronto, ON, Canada., Institute of Pathology, University Erlangen-Nürnberg, Erlangen, Germany., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA., Barts Cancer Institute ECMC, Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, UK., Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, Madrid, Spain., Cedars-Sinai Samuel Oschin Cancer Institute, Los Angeles, CA, USA., Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada., Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA., Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, Madrid, Spain., Institut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, Paris, France.

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