Tumor Mutational Burden Predicts the Outcome of Patients With Muscle-invasive bladder Cancer Undergoing Immune-checkpoint Inhibitor-Based Neoadjuvant Therapy.

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

Published in

Clinical genitourinary cancer. Volume 24. Issue 7. Pages 102638. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

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.
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.
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.
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.

PMID:
42632232
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.