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Molecular Subtyping for Predicting Pathological Upstaging and Survival Outcomes in Clinically Organ-confined Bladder Cancer Patients Undergoing Radical Cystectomy

  • 0Erasmus University Medical Center, Rotterdam, The Netherlands.
European Urology Open Science +

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February 12, 2025

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February 12, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Molecular subtyping using Decipher Bladder can identify bladder cancer patients at higher risk for upstaging. Luminal tumors show less aggressive disease, with lower upstaging rates and better overall survival after radical cystectomy compared to nonluminal tumors.

Area Of Science

  • Urology
  • Genomics
  • Oncology

Background

  • Bladder cancer staging is often inaccurate, leading to understaging in many patients.
  • Molecular subtyping has shown promise in improving the accuracy of clinical staging.
  • This study validates Decipher Bladder for upstaging assessment in patients undergoing radical cystectomy without neoadjuvant therapy.

Purpose Of The Study

  • To evaluate the Decipher Bladder genomic subtyping classifier (GSC) for pathological upstaging in patients with high-grade urothelial carcinoma.
  • To assess the primary endpoint of upstaging to non-organ-confined (NOC) disease after radical cystectomy (RC).
  • To explore secondary endpoints including overall survival (OS) and upstaging to muscle-invasive bladder cancer (MIBC+) in clinically non-muscle-invasive bladder cancer (cNMIBC) cases.

Main Methods

  • Decipher Bladder GSC was performed on bladder tumor specimens from 226 patients (134 cNMIBC, 92 cT2) undergoing RC without neoadjuvant chemotherapy.
  • The study analyzed pathological upstaging to NOC disease (pT3+ and/or N+) as the primary endpoint.
  • Secondary endpoints included OS and upstaging to MIBC+ disease (pT2+ and/or N+) in cNMIBC cases.

Main Results

  • Overall upstaging to NOC disease occurred in 33% of patients (19% cNMIBC, 53% cT2).
  • Molecular subtyping identified luminal (138) and nonluminal (88) tumors. Upstaging to NOC was higher in nonluminal tumors (41%) versus luminal tumors (28%) (p=0.04).
  • Upstaging to MIBC+ in cNMIBC was lower in luminal vs. nonluminal tumors (32% vs. 51%, p=0.03). Nonluminal tumors correlated with worse OS (p<0.05).

Conclusions

  • Luminal bladder tumors represent less aggressive disease, indicated by lower pathological upstaging rates and favorable OS post-RC compared to nonluminal tumors.
  • Molecular subtyping with Decipher Bladder provides valuable prognostic information for bladder cancer patients.
  • These findings support the use of genomic subtyping to refine staging and treatment decisions in bladder cancer.

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