A Luminal Non-Coding RNA-Based Genomic in Patients with Clinically Organ-Confined Bladder Cancer Treated with Radical Cystectomy - Expert Commentary

Classifying bladder cancers based on expression-based molecular subtypes represents an important framework for understanding the biology. A recent study evaluated a classifier for identifying favorable outcomes in bladder cancer patients undergoing radical cystectomy (RC). The research analyzed transcriptome-wide expression profiling using Decipher Bladder on 226 patients with high-grade, clinically organ-confined urothelial carcinoma who underwent RC without neoadjuvant therapy.

The study included 134 patients with clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 with cT2 disease. Using lncRNA expression profiles, the classifier identified 60 patients with luminal favorable subtype, characterized by robust gene expression patterns associated with a less aggressive cancer phenotype. Key findings from multivariate analysis showed that the Luminal favorable subtype had lower odds of upstaging to pathological T3+ disease (OR 0.32, 95% CI 0.12-0.82; P = 0.02), Reduced risk of any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), Lower risk of upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05) and a significantly better overall survival (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007)

Luminal favorable tumors showed higher FGFR3 signaling activity and were more common in non-muscle-invasive disease (35%) compared to cT2 disease (14%). Only 17% of luminal favorable cases were upstaged to non-organ-confined disease at RC, with 10% showing lymph node positive disease.

This study demonstrates the promise of classifiers in identifying less aggressive tumor biology, which could help inform treatment decisions for bladder cancer patients.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. de Jong JJ, Proudfoot JA, Daneshmand S, Svatek RS, Naryan V, Gibb EA, Davicioni E, Joshi S, Dahmen A, Li R, Inman BA, Shah P, Chaplin I, Wright J, Lotan Y. BJU Int. 2024 Nov 1. doi: 10.1111/bju.16572. A luminal non-coding RNA-based genomic classifier confirms favourable outcomes in patients with clinically organ-confined bladder cancer treated with radical cystectomy. Online ahead of print. PMID: 39485082
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