1740P Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy for Invasive Bladder Cancer (BPT-ART): an Open-Label, Single-Arm, Multicenter, Phase II Trial

Radical cystectomy (RC) is standard care for patients with muscle invasive bladder cancer (BC) or highest-risk non-muscle invasive BC. However, optimal care for bladder preservation or intolerance to RC remains uncertain. Atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor with synergistic antitumor activity along with radiation therapy (RT), is a promising treatment. In this multicenter, phase 2 trial, we recruited patients with clinical (c)T1-3N0M0 invasive BC who were unfit for or refused RC. Patients received RT (41.4 Gy in 23 fractions to the small pelvis and 16.2 Gy in 9 fractions to the whole bladder) combined with intravenous atezolizumab 1200mg every 3 weeks. After 24 treatment weeks, response was assessed using CT imaging and transurethral bladder resection. The secondary endpoint, pathological complete response (pCR), was evaluated before the primary endpoint (progression-free survival rate). Tumor PD-L1 expression was assessed using the tumor-infiltrating immune cell (IC) score. Forty-five patients enrolled between January 2019 and May 2021 were analyzed. The most common cT stage was T2 (73.3%), followed by T1 (15.6%) and T3 (11.1%). Most tumors were single (77.8%) or small (<3cm) (57.8%), with no concomitant carcinoma in situ (CIS) (88.9%). Thirty-eight patients (84.4%) achieved pCR after 24 weeks of treatment. Patients with high PD-L1 expression (IC score >1) had higher pCR rates than those with low expression (IC score 0) (95.8% vs. 71.4%), with low rates (60.0%) in patients with CIS. Adverse events (AEs) were observed in 93.3% of patients and the most common were diarrhea (55.6%), followed by pollakiuria (42.2%) and dysuria (20.0%). The frequency of grade 3 AEs was 13.3%, with no grade 4 events. RT combined with atezolizumab resulted in a favorable high proportion of pCR with acceptable toxicity. This protocol will provide a promising new alternative for bladder preservation in BC patients.