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Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical
Moritz J Reike1, Daniele Raggi2, Chiara Mercinelli2
1Department of Urologic Sciences, University of British Columbia, Vancouver, Canada; Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Germany.
Clinical Genitourinary Cancer
|October 25, 2024
Summary
This study analyzed bladder cancer patients relapsing after neoadjuvant pembrolizumab. Neuroendocrine-like tumors showed poor outcomes, while Claudin-low tumors had fewer recurrences, identifying key genes linked to relapse.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Neoadjuvant pembrolizumab (anti-PD-1) before radical cystectomy (RC) shows promise for muscle-invasive bladder cancer (MIBC).
- Specific molecular subtypes and immune signatures correlate with favorable survival in the PURE-01 trial.
- Detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab is not well-characterized.
Purpose of the Study:
- To characterize the tumor biology of patients with MIBC who relapse after neoadjuvant pembrolizumab and RC.
- To identify molecular subtypes and gene expression signatures associated with relapse in this patient cohort.
Main Methods:
- Analysis of microarray data from transurethral resection of bladder tumor (TURBT) and matched RC tissues (n=102) from relapsed PURE-01 patients.
- Gene expression signatures and molecular subtyping were performed.
- Kaplan-Meier method and t-tests were used for survival and significance analysis.
Main Results:
- Out of 102 patients, 19% (n=19) experienced disease relapse.
- Neuroendocrine-like molecular subtypes were associated with the worst outcomes.
- Claudin-low tumors showed only one recurrence; KRT20, H19, CXCL9, and CXCL11 were identified as relapse-associated genes.
Conclusions:
- This study details the tumor biology of MIBC patients relapsing after neoadjuvant pembrolizumab and RC.
- Distinct gene expression patterns are linked to relapse, potentially aiding in predicting treatment response.
- Findings may inform treatment decisions for patients receiving neoadjuvant immunotherapy.

