Radiation Therapy Combined with Immunotherapy Before Radical Cystectomy in Locally Advanced Bladder Cancer: A Prospective, Single-arm, Multicenter, Phase 2 Trial (RACE-IT).

BACKGROUND AND

OBJECTIVE

Patients with locally advanced bladder cancer have a poor prognosis despite radical surgery. Early data on neoadjuvant immunotherapy are promising, with possible synergistic effects with radiation therapy. Therefore, this prospective multicenter phase 2 trial evaluated, for the first time, the feasibility, safety, and efficacy of neoadjuvant radioimmunotherapy before radical cystectomy.

METHODS

Patients with locally advanced urothelial bladder cancer (cT3/4 cN0/N+ cM0) eligible for radical cystectomy but unfit or refusing neoadjuvant cisplatin-based chemotherapy were included in this prospective phase 2 trial. Patients received four cycles of nivolumab 240 mg every 2 wk combined with radiotherapy of the pelvis with a maximum dose of 50.4 Gy. Patients underwent radical cystectomy with pelvic lymphadenectomy between weeks 11 and 15. The primary endpoint was feasibility, defined as a minimum completed treatment rate of >70% at the end of week 15.

KEY FINDINGS AND LIMITATIONS: Thirty-three patients were included. For the primary endpoint and efficacy analysis, 31 patients were eligible. The trial met its primary endpoint with a completed treatment rate of 87% (27/31). The pathological response rates were 39% with ypT0 ypN0 cM0, 58% with ≤ypT1 ypN0 cM0, and 74% with ≤ypT2 ypN0 cM0. Immune-related adverse events of all grades occurred in 55%, and grade 3/4 adverse events occurred in 33% of patients. There were no treatment-related deaths.

CONCLUSIONS AND CLINICAL IMPLICATIONS: By meeting its primary endpoint, this trial demonstrated for the first time the feasibility and safety of neoadjuvant radioimmunotherapy prior to radical cystectomy in patients with locally advanced bladder cancer, warranting further investigation in a randomized setting.