Treatment of patients with muscle-invasive bladder cancer (MIBC) includes cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Molecular subtypes have been associated with patient outcomes after NAC and RC, but the reported results have been highly inconsistent.
To evaluate the association of molecular subtypes from different classifiers with overall survival (OS) among patients with MIBC who underwent RC.
We analyzed gene expression data generated from transurethral resection of MIBC from a previously assembled and published meta-cohort, NACmeta (N = 601, 247 treated with NAC+RC and 354 RC without NAC), where extended follow-up was available. Molecular subtypes were assigned using the Genomic Subtyping Classifier (GSC), the Consensus Classifier, The Cancer Genome Atlas (TCGA) Classifier, and the Lund Classifier. For survival analysis, inverse probability weighting was used to balance the clinical NAC and non-NAC patient groups.
A high consistency in gene expression patterns and nomenclature was observed between luminal-like subtypes, defined as GSC-Luminal, Consensus-Luminal Papillary (LumP), TCGA Luminal-Papillary (LumP) and Lund-UroA, but not for basal-like subtypes such GSC-Basal, Consensus Basal/Squamous, TCGA-Basal/Squamous and Lund-Basal/Squamous. Patients with luminal-like subtypes demonstrated no difference in 3-year OS when treated with or without NAC (P = 0.7 for GSC, P = 0.94 for Consensus, P = 0.87 for TCGA and P = 0.66 for Lund-UroA, respectively).
Luminal-like molecular subtypes identify a subgroup of MIBC patients who do not appear to benefit from current NAC regimens, even for locally advanced disease. In addition, we were able to illustrate differences in subtyping nomenclature that are not reflected in the underlying biological definition of the subtypes.
Muscle-invasive bladder cancer exhibits molecular diversity, and various classifications identify different groups who do not benefit from chemotherapy. On the other hand, there is a high inconsistency in the way cancer groupings are named.
Urologic oncology. 2024 Mar 12 [Epub ahead of print]
Moritz J Reike, Joep J de Jong, Tarek A Bismar, Stephen A Boorjian, Omar Y Mian, Jonathan L Wright, Marc A Dall'Era, Hristros Z Kaimakliotis, Yair Lotan, Joost L Boormans, Peter C Black, Ewan A Gibb
Department of Urologic Sciences, University of British Columbia, Vancouver, Canada; Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany. Electronic address: ., Department of Urology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Department of Pathology and Laboratory Medicine, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada., Department of Urology, Mayo Clinic, Rochester, USA., Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, USA., Division of Oncology, Department of Medicine, University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, USA., Department of Urology, University of Texas Health San Antonio, San Antonio, USA., Department of Urology, Indiana University, Indianapolis, USA., Department of Urology, University of Texas Southwestern Medical Center, Dallas TX, USA., Department of Urologic Sciences, University of British Columbia, Vancouver, Canada., Veracyte Inc., San Francisco, USA.