Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2024
Association of Molecular Subtypes with Pathologic Response, PFS, and OS in a Phase II Study of COXEN with Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer-A Systematic Review of the Current Status.International journal of molecular sciences · 2024Pooled it
- Histopathological Response After Neoadjuvant Chemotherapy for High-Risk Soft-Tissue Sarcomas: A Secondary Analysis of a Randomized Clinical Trial.JAMA network open · 2025Trial
- Ex Vivo Microtumor Testing to Predict Chemotherapy Responses in Patients with Bladder Cancer.European urology open science · 2026Article
- Proliferation- and cytotoxic immune signatures identify chemotherapy-responsive bladder tumors in a molecular subtype dependent manner.NPJ precision oncology · 2026Article
- Machine learning-based integration of transcriptome and digital pathology for predicting chemoresistance in muscle-invasive bladder cancer.Experimental & molecular medicine · 2026Article
- Predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer via interpretable multimodal deep learning.NPJ digital medicine · 2025Article
- Natural history of bladder cancer: Validation of the multiple pathway model in multi-omics era.Urologic oncology · 2025Review
- Immunohistochemistry-based molecular subtypes of urothelial carcinoma derive different survival benefit from platinum chemotherapy.The journal of pathology. Clinical research · 2025Article
- The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers.Current oncology (Toronto, Ont.) · 2024Review
- Biomarker challenges in the pursuit of personalized neoadjuvant chemotherapy for muscle-invasive bladder cancer: conclusions from SWOG S1314.Translational andrology and urology · 2024Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
purposeThe Coexpression Extrapolation (COXEN) gene expression model with chemotherapy-specific scores [for methotrexate, vinblastine, adriamycin, cisplatin (ddMVAC) and gemcitabine/cisplatin (GC)] was developed to identify responders to neoadjuvant chemotherapy (NAC). We investigated RNA-based molecular subtypes as additional predictive biomarkers for NAC response, progression-free survival (PFS), and overall survival (OS) in patients treated in S1314. EXPERIMENTAL
designA total of 237 patients were randomized between four cycles of ddMVAC (51%) and GC (49%). On the basis of Affymetrix transcriptomic data, we determined subtypes using three classifiers: TCGA (k = 5), Consensus (k = 6), and MD Anderson (MDA; k = 3) and assessed subtype association with path response to NAC and determined associations with COXEN. We also tested whether each classifier contributed additional predictive power when added to a model based on predefined stratification (strat) factors (PS 0 vs. 1; T2 vs. T3, T4a).
resultsA total of 155 patients had gene expression results, received at least three of four cycles of NAC, and had pT-N response based on radical cystectomy. TCGA three-group classifier basal-squamous (BS)/neuronal, luminal (Lum), Lum infiltrated, and GC COXEN score yielded the largest AUCs for pT0 (0.59, P = 0.28; 0.60, P = 0.18, respectively). For downstaging (<pT2), the three-category Consensus classifier [BS/neuroendocrine (NE)-like, Lum, stroma-rich] increased the AUC from 0.57 (strat factors alone) to 0.61 (P = 0.10). The MDA classifier AUC was 0.63 (P = 0.18) and the GC COXEN score AUC was 0.62 (P = 0.23), but neither significantly improved the AUC. There was no statistically significant association of stratification factors and subtypes with PFS or OS.
conclusionsThe Consensus classifier, based in part on the TCGA and MDA classifiers, modestly improved prediction for pathologic downstaging but subtypes were not associated with PFS or OS.
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