Year: 2019
Type: article
Abstract: 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.
Source: European Urology
Authors: 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, Mattias Aine, Hikmat Al-Ahmadie, Yves Allory, Joaquim Bellmunt, Isabelle Bernard-Pierrot, Peter C. Black, Mauro A.A. Castro, Keith S. Chan, Woonyoung Choi, Bogdan Czerniak, Colin P. Dinney, Lars Dyrskjøt, Pontus Eriksson, Jacqueline Fontugne, Ewan A. Gibb, Clarice S. Groeneveld, Arndt Hartmann, Katherine A. Hoadley, Mattias Höglund, Aurélie Kamoun, Jordan Kardos, Jaegil Kim, William Y. Kim, David J. Kwiatkowski, Thierry Lebret, Seth P. Lerner, Fredrik Liedberg, Núria Malats, David J. McConkey, Qianxing Mo, Thomas Powles, François Radvanyi, Francisco X. Real, Aurélien de Reyniès, A. Gordon Robertson, Arlene Siefker-Radtke, Nanor Sirab, Roland Seiler, Gottfrid Sjödahl, Ann Taber, John Weinstein, Alexandre Zlotta
Institutions: La Ligue Contre le Cancer, Centre National de la Recherche Scientifique, Université Paris Sciences et Lettres, Biologie cellulaire et Cancer, Institut Curie, Lund University, Skåne University Hospital, BC Cancer Agency, Canada's Michael Smith Genome Sciences Centre, University Hospital of Bern, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Universidade Federal do Paraná, Memorial Sloan Kettering Cancer Center, Johns Hopkins University, Moffitt Cancer Center, Mount Sinai Hospital, University Health Network, University of Toronto, Friedrich-Alexander-Universität Erlangen-Nürnberg, The University of Texas MD Anderson Cancer Center, Harvard University, Dana-Farber Brigham Cancer Center, Queen Mary University of London, The Royal Free Hospital, Barts Cancer Institute, Spanish National Cancer Research Centre, Centro de Investigación Biomédica en Red de Cáncer, Cedars-Sinai Medical Center, University of British Columbia, Aarhus University Hospital, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Broad Institute, Brigham and Women's Hospital, Université de Versailles Saint-Quentin-en-Yvelines, Hôpital Foch, Hôpital René Huguenin
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
OpenAlex ID: W2975497362