Patients (Pts) with locally advanced bladder cancer (BC) have a poor prognosis despite radical surgical therapy. Early data on neoadjuvant immunotherapy in muscle invasive BC is promising, while there are indications of synergistic effects of radiation and immunotherapy. This trial evaluates the feasibility, safety and efficacy of neoadjuvant radio-immunotherapy (RIT) following radical cystectomy (RCX) in patients with locally advanced, muscle invasive BC.
Patients with locally advanced urothelial BC (cT3/4 cN0/N+ cM0, eligible for RCX, unfit for or refusing neoadjuvant chemotherapy) were included in this prospective, single arm, phase II-trial. Pts were treated with Nivolumab 240mg intravenously every two weeks for 4 cycles, starting one week before radiotherapy of the bladder/pelvis with 50.4 Gy, followed by RCX with standardized pelvic lymphadenectomy. Primary endpoint is the rate of Pts with completed treatment (RIT and RCX) at the end of week 15. Secondary endpoints include overall response rate (ORR), pathological response rates, disease free survival (DFS) and toxicity.
Of 33 treated Pts, 32 (97%) were ≥cT3/4 and 10 (30.3%) were lymph node positive (cN+). For primary endpoint and efficacy analysis, 31 Pts were eligible. Primary endpoint of completed treatment (RIT and RCX) in time at the end of week 15 was reached in 27/31 (87.1%) Pts. Median number of nivolumab cycles was 4. The radiological ORR was 70.9% (CR 16.1%, PR 54.8%, SD 25.8% and PD 3.2%). Pathological response rate was ypT0 38.7% and ≤ ypT1 58.1%. While survival data is immature, DFS rate at 12 months was 90.6%. Any-grade treatment-related AEs (TRAEs) occurred in 54.5 % of all 33 patients. TRAEs were mostly grade 1-2. Most common TRAEs were thyroid and gastrointestinal disorders (each 15.2%) and skin reactions (33.3%). TRAEs led to Nivolumab discontinuation in 8 (25.8%) Pts.
The trial met its primary endpoint. Neoadjuvant radio-immunotherapy followed by radical cystectomy in locally advanced bladder cancer patients is feasible and safe.