Final results from a phase II study of tislelizumab combined with radiotherapy as bladder-preserving treatment for high-risk non–muscle-invasive bladder cancer patients unresponsive to Bacillus Calmette-Guerin.

4599 Background: Radical cystectomy (RC) was the standard of care for high-risk non-muscle-invasive bladder cancer (HR NMIBC) patients with Bacillus Calmette-Guerin (BCG)-unresponsive papillary tumors. Clinical unmet need was to explore non-surgical treatment options for patients who were ineligible for or declined RC. Our study was established to evaluate the efficacy and safety of tislelizumab combined with radiotherapy as bladder-preserving treatment for HR NMIBC patients unresponsive to BCG. Methods: This open-label, single arm phase II study enrolled HR NMIBC patients with BCG-unresponsive papillary tumors (high-grade Ta or T1 tumors without carcinoma in situ). The papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Within 2 weeks after TURBT, eligible patients received tislelizumab 200 mg in day 1 (D1), every 21 days for eight cycles and a total radiotherapy dose of 60-66 GY in 30-33 fractions over seven weeks. The primary endpoint was disease-free survival (DFS) rate at 12 months (defined as no reappearance of high grade or T1 tumors or clinical stage development after the therapy). Secondary endpoints were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 50% and the study would enroll 32 patients to meet the primary endpoint. Results: Between September 4, 2020, and December 11, 2024, 32 patients (26 81.2% men and 6 19.8% women) who had received a median of eleven (IQR 7-22) previous BCG instillations were enrolled. Patients received a median of 8 cycles (IQR 8–8) of tislelizumab and of radiotherapy doses of 62.0 GY (IQR 62.0–64.0) . Median follow-up was 28.8 months (19.7-43.8). The DFS rate at 12 months was 90.6% (95%CI, 79.8%-99.6%), at 24 months was 70.2% (95%CI, 50.1%-83.4%). The bladder-preservation rate at 24 months was 93.2% (95%CI, 75.4%-98.3%). The OS rate at 24 months was 100% (95%CI, 100%-100%). The OS rate at 36 months was 90.5% (95%CI, 67.0%-97.6%). Treatment-related adverse events (TRAEs) occurred in 27 (84.4%) of 32 patients, 7 (21.9%) patients had a grade 3 TRAEs. The most common 3 TRAEs were diarrhea (9.4%), radiocystitis (3.1%), leukopenia (3.1%) and liver function damage (3.1%) without grade 4-5 TRAEs. Conclusions: Our final results supported the use of tislelizumab combined with radiotherapy as a promising bladder-preserving therapy for BCG-unresponsive HR NMIBC patients who were ineligible for or decline RC. Clinical trial information: ChiCTR2000035275.