Journal Article Observational Study Ppublish
PubMed: 42632232 DOI: 10.1016/j.clgc.2026.102638
Tumor Mutational Burden Predicts the Outcome of Patients With Muscle-invasive bladder Cancer Undergoing Immune-checkpoint Inhibitor-Based Neoadjuvant Therapy.
Clin Genitourin Cancer 24(7):102638
Authors: Chiara Mercinelli, Giuseppe Basile, Giovanni L Pastorino, Antonio Cigliola, Brigida A Maiorano, Valentina Tateo, Michela Piacentini, Debora Serafin, Gualtiero Guandalini, Roberta Lacava, Gaia Latini, Maurizio Colecchia, Alberto Briganti, Marco Moschini, Francesco Montorsi, Dean Pavlick, Jeffrey S Ross, Andrea Necchi
Affiliations
- Università Vita-Salute San Raffaele, Milan, Italy; Medical Oncology Department, Comprehensive Cancer Center, IRCCS San Raffaele Hospital, Milan, Italy.
- Urology Department, The Royal Free London Foundation Trust, London, UK; Urology Department, IRCCS Ospedale San Raffaele, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy; Medical Oncology Department, Comprehensive Cancer Center, IRCCS San Raffaele Hospital, Milan, Italy.
- Medical Oncology Department, Comprehensive Cancer Center, IRCCS San Raffaele Hospital, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy; Medical Oncology Unit 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy; Department of Pathology and Laboratory Medicine, IRCCS Ospedale San Raffaele, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan, Italy; Urology Department, IRCCS Ospedale San Raffaele, Milan, Italy.
- Urology Department, IRCCS Ospedale San Raffaele, Milan, Italy.
- Foundation Medicine Inc, Cambridge, MA.
- Foundation Medicine Inc, Cambridge, MA; Upstate Medical University, Syracuse, NY.
Abstract
INTRODUCTION
Immune checkpoint inhibitors (ICI) have demonstrated meaningful activity as neoadjuvant therapy in muscle-invasive bladder cancer (MIBC). Identifying patients most likely to respond to ICI-based neoadjuvant strategies remains an unmet need.
MATERIALS AND METHODS
Tumor mutational burden (TMB) from baseline transurethral resection of bladder (TURB) tumor samples of MIBC patients treated with neoadjuvant ICI across PURE-01 (NCT02736266), SURE-02 (NCT05535218), and NURE-Combo (NCT04876313) trials was analyzed. Probabilities of complete response ( CR; yT0N0‑x at radical cystectomy or re-TURB tumor), event‑free survival, and overall survival were assessed across different TMB cutoffs. Logistic regression models evaluated predictors of CR.
RESULTS
202 patients (85% male, median age 66) were included. 57% had cT2 disease. Median TMB was 10.5 mut/Mb; 88 patients (44%) achieved CR. Optimal TMB threshold for CR was 13 mut/Mb with a predicted probability (PP) of 43% (95% confidence interval [CI]: 36.6-50.6); higher TMB showed incremental PP. At TMB ≥ 20 threshold, PP was 54% (95% CI: 43.7-63.1), with significant association with CR at multivariable analysis (AUC: 0.65). No significant effect by therapeutic regimen was observed. With a median follow-up of 63 months (interquartile range 25-77), 60m-event‑free survival for TMB ≥ 20 pts was 97% (95% CI: 90.4-100) versus 73% (95% CI: 65.6-80.7), P=0.03, and 60m-overall survival was 100% versus 78.8% (95% CI: 71.9-86.4), P = .01.
CONCLUSIONS
Our analysis support TMB as a clinically informative biomarker in MIBC patients treated with neoadjuvant ICI, identifying a subset of exceptional responders associated with higher TMB levels.
MeSH
Urinary Bladder, Urinary Bladder Neoplasms, Muscles, Probability, Neoplasms, Immunotherapy, Immune Checkpoint Inhibitors, Prostatic Neoplasms, Neoadjuvant Therapy, Kidney Neoplasms, Precision Medicine, Therapeutics