IBCN 2023: Alignment Of Molecular Subtypes Across Multiple Bladder Cancer Subtyping Classifiers

(UroToday.com) Guideline-recommended treatment for muscle-invasive bladder cancer (MIBC) patients includes cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). There is a need for markers to predict response to neoadjuvant chemotherapy and previously published reports demonstrated a high degree of inconsistency among reported subtype-specific outcomes.

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 neoadjuvant chemotherapy+radical cystectomy and 354 radical cystectomy without neoadjuvant chemotherapy), where extended follow-up was available. Molecular subtypes were assessed using Genomic Subtyping Classifier (GSC), the Consensus Classifier, The Cancer Genome Atlas (TCGA) and the Lund Classifier. For survival analysis, inverse probability weighting was used to balance the clinical characteristics of the neoadjuvant chemotherapy and non-NAC patient groups.

A high consistency in transcriptomic 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 LundBasal/Squamous. Patients with luminal-like subtypes demonstrated no differences in 3-year survival whether they had received neoadjuvant chemotherapy (p=0.7 for GSC, p=0.94 for Consensus, p=0.87 for TCGA and p=0.66 for Lund-UroA, respectively). Patients with ≥pT3 disease at radical cystectomy who were classified as GSC-Luminal did not show a significant survival improvement with neoadjuvant chemotherapy (p=0.21).

Luminal-like molecular subtypes, including the GSC-Luminal, Consensus LumP, TCGA-LumP and the Lund-UroA, identify a subgroup of MIBC patients who do not appear to benefit from current neoadjuvant chemotherapy 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

Presented by: Moritz Reike, Ruhr-University Bochum, Germany

Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network (IBCN) Annual Meeting, September 29-30, 2023, Montreal, Canada