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A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

Kamoun, Aurélie ; Reyniès, Aurélien de ; Allory, Yves ; Sjödahl, Gottfrid LU ; Gordon Robertson, A. ; Seiler, Roland ; Hoadley, Katherine A. ; Groeneveld, Clarice S. ; Al-Ahmadie, Hikmat and Choi, Woonyoung , et al. (2020) In European Urology 77(4). p.420-433
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... (More)

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.

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contributor
LU
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Consensus, Molecular taxonomy, Muscle-invasive bladder cancer, Transcriptomic classifier
in
European Urology
volume
77
issue
4
pages
14 pages
publisher
Elsevier
external identifiers
  • pmid:31563503
  • scopus:85072635570
ISSN
0302-2838
DOI
10.1016/j.eururo.2019.09.006
language
English
LU publication?
yes
id
f2d670e5-790e-4022-a244-df6fe5a6361a
date added to LUP
2019-10-07 14:14:02
date last changed
2024-04-16 20:20:40
@article{f2d670e5-790e-4022-a244-df6fe5a6361a,
  abstract     = {{<p>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.</p>}},
  author       = {{Kamoun, Aurélie and Reyniès, Aurélien de and Allory, Yves and Sjödahl, Gottfrid and Gordon Robertson, A. and Seiler, Roland and Hoadley, Katherine A. and Groeneveld, Clarice S. and Al-Ahmadie, Hikmat and Choi, Woonyoung and Castro, Mauro A.A. and Fontugne, Jacqueline and Eriksson, Pontus and Mo, Qianxing and Kardos, Jordan and Zlotta, Alexandre and Hartmann, Arndt and Dinney, Colin P. and Bellmunt, Joaquim and Powles, Thomas and Malats, Núria and Chan, Keith S. and Kim, William Y. and McConkey, David J. and Black, Peter C. and Dyrskjøt, Lars and Höglund, Mattias and Lerner, Seth P. and Real, Francisco X. and Radvanyi, François}},
  issn         = {{0302-2838}},
  keywords     = {{Consensus; Molecular taxonomy; Muscle-invasive bladder cancer; Transcriptomic classifier}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{420--433}},
  publisher    = {{Elsevier}},
  series       = {{European Urology}},
  title        = {{A Consensus Molecular Classification of Muscle-invasive Bladder Cancer}},
  url          = {{http://dx.doi.org/10.1016/j.eururo.2019.09.006}},
  doi          = {{10.1016/j.eururo.2019.09.006}},
  volume       = {{77}},
  year         = {{2020}},
}