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Cited by 1,359Bladder and Urothelial Cancer TreatmentsBreast Cancer Treatment StudiesUrinary and Genital Oncology Studies

A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

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Kamoun, Aurélie, de Reyniès, Aurélien, Allory, Yves, Sjödahl, Gottfrid, Robertson, A. Gordon, Seiler, Roland, Hoadley, Katherine A., Groeneveld, Clarice S. +64 more·2020·European Urology
DOI 10.1016/j.eururo.2019.09.006PMC PMC7690647

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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.

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  • The basal subtype of BLCA is known to be sensitive to immunotherapy and exhibits higher immune cell infiltration.

    “which is known to be sensitive to immunotherapy and exhibits higher immune cell infiltration 43”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [43]

    The Results (Transcriptomic characterization; page not supplied) report immune infiltration in Ba/Sq tumors. The Results (Therapeutic opportunities; page not supplied) say their immune-marker expression suggests they might be more responsive to immunotherapy, but also state that no consensus class had an expression profile clearly indicating response. Thus, the claim overstates immunotherapy sensitivity as established. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Kamoun, A., de Reyniès, A., Allory, Y., Sjödahl, G., Robertson, A. G., Seiler, R., Hoadley, K. A., Groeneveld, C. S., Al-Ahmadie, H., Choi, W., Castro, M. A. A., Fontugne, J., Eriksson, P., Mo, Q., Kardos, J., Zlotta, A., Hartmann, A., Dinney, C. P., Bellmunt, J., Powles, T., Malats, N., Chan, K. S., Kim, W. Y., McConkey, D. J., Black, P. C., Dyrskjøt, L., Höglund, M., Lerner, S. P., Real, F. X., Radvanyi, F., Aine, M., Al-Ahmadie, H., Allory, Y., Bellmunt, J., Bernard-Pierrot, I., Black, P. C., Castro, M. A. A., Chan, K. S., Choi, W., Czerniak, B., Dinney, C. P., Dyrskjøt, L., Eriksson, P., Fontugne, J., Gibb, E. A., Groeneveld, C. S., Hartmann, A., Hoadley, K. A., Höglund, M., Kamoun, A., Kardos, J., Kim, J., Kim, W. Y., Kwiatkowski, D. J., Lebret, T., Lerner, S. P., Liedberg, F., Malats, N., McConkey, D. J., Mo, Q., Powles, T., Radvanyi, F., Real, F. X., de Reyniès, A., Robertson, A. G., Siefker-Radtke, A., Sirab, N., Seiler, R., Sjödahl, G., Taber, A., Weinstein, J., & Zlotta, A.
Affiliations
  • Broad Institute (US)
  • Hôpital René Huguenin (FR)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
ORCID
Venue
European Urology
Publisher
Elsevier BV
Published
2020-04
Volume
77
Issue
4
Pages
420-433
ISSN
0302-2838 (ISSN-L)
DOI
10.1016/j.eururo.2019.09.006
PMC
PMC7690647
OpenAlex
W2975497362
Cited by
1,359
References
1
Citations by year
2026: 169 · 2025: 191 · 2024: 211 · 2023: 233 · 2022: 215 · 2021: 210 · 2020: 109 · 2019: 21
FWCI
136.89
Type
journal article
Language
en
Open access
Licence
Locations
  • European Urology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • HAL (submittedVersion, other-oa)
  • Lund University Publications (Lund University) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-nd)
Funders
  • National Cancer Institute
  • Cancerfonden (2017/278)
  • National Human Genome Research Institute
Topics
  • Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Surgery › Urinary and Genital Oncology Studies
Keywords
muscle-invasive bladder cancer, molecular classification, consensus molecular subtypes, transcriptomic profiles, prognostic stratification, tumor immune infiltration, oncogenic mechanisms
MeSH terms
Aged, Aged, 80 and over, Urinary Bladder Neoplasms, Female, Humans, Male, Middle Aged, Neoplasm Invasiveness, Retrospective Studies, Consensus

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