Clinical genitourinary cancer · 2026
Tumor Mutational Burden Predicts the Outcome of Patients With Muscle-invasive bladder Cancer Undergoing Immune-checkpoint Inhibitor-Based Neoadjuvant Therapy.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Mercinelli Chiara, Basile Giuseppe, Pastorino Giovanni L, Cigliola Antonio, Maiorano Brigida A, Tateo Valentina, Piacentini Michela, Serafin Debora, Guandalini Gualtiero, Lacava Roberta, Latini Gaia, Colecchia Maurizio, Briganti Alberto, Moschini Marco, Montorsi Francesco, Pavlick Dean, Ross Jeffrey S, Necchi Andrea
Аннотация
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.
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.