Multicenter phase 2 trial of ipilimumab and nivolumab followed by chemoradiotherapy as bladder-sparing treatment in muscle-invasive bladder cancer

Radical cystectomy for muscle-invasive bladder cancer (MIBC) carries substantial perioperative complication risks, alongside major changes in urinary and sexual function. Chemoradiotherapy (CRT) is used as a bladder-sparing alternative but is usually reserved for small, solitary tumors. The multicenter phase 2 INDIBLADE trial in The Netherlands evaluated bladder-sparing treatment among 50 patients with stage II/III (cT2-4aN0-2) MIBC, using induction ipilimumab plus nivolumab followed by CRT. After a median follow-up of 28.7 months, the primary endpoint of 2-year bladder-intact event-free survival (BI-EFS) rate was met at 78% (95% CI 0.67-0.90). Two-year overall survival rate was 96% (95% CI 0.91-1.00). Grade 3-4 immune-related adverse events occurred in 24% of patients and grade 3-4 CRT-related adverse events occurred in 7%. Absence of detectable circulating tumor DNA (ctDNA) after induction immunotherapy was associated with BI-EFS. The authors conclude that induction combination immunotherapy followed by CRT can be an effective bladder-sparing treatment in MIBC, and response can be monitored by ctDNA.