Neoadjuvant chemoradiotherapy plus programmed cell death protein-1 blockade versus chemoradiotherapy alone for muscle-invasive bladder cancer: a real-world comparative study.

[INTRODUCTION] Muscle-invasive bladder cancer (MIBC) has a high risk of recurrence and mortality despite radical cystectomy. Neoadjuvant chemoradiotherapy (NACRT) offers has been investigated as a bladder-preserving strategy in selected patients; however, in this study, all patients underwent radical cystectomy following NACRT, and programmed cell death protein-1 (PD-1) inhibitors have shown antitumor activity in urothelial carcinoma. Combining NACRT with PD-1 blockade may enhance tumor response; however, its pathological benefits and short-term safety remain unclear. This study aimed to compare pathological response and short-term safety between NACRT alone and NACRT combined with PD-1 blockade (NACRT + PD-1) in patients with MIBC.

[METHODS] A retrospective review was conducted for 59 consecutive patients with MIBC (cT2-T4aN0M0) treated at the First Affiliated Hospital of Soochow University between January 2021 and December 2024. Twenty-seven patients received NACRT alone, and 32 received NACRT plus a PD-1 inhibitor-toripalimab (n=18) or tislelizumab (n=14). Chemotherapy comprised gemcitabine 1,000 mg/m² (days 1 and 8) and cisplatin 70 mg/m² (days 2-3) every 21 days for ≥3 cycles. Intensity-modulated pelvic radiotherapy delivered 45 Gy in 25 fractions plus a weekly boost (10 Gy in five fractions) to the bladder. The PD-1 antibody (toripalimab 200 mg or tislelizumab 240 mg) was infused on day 8 of each cycle. The primary endpoints were pathological downstaging rate (PDR, ≤ypT1/Tis/TaN0M0) and pathological complete response rate (PCRR, ypT0N0M0). The secondary endpoint was treatment-related adverse events (AEs) graded using the Common Terminology Criteria for Adverse Events version 5.0. Group comparisons used χ², Fisher's exact, or non-parametric tests as appropriate (two-sided, α=0.05).

[RESULTS] Baseline demographics and clinical characteristics were balanced between the groups (all p > 0.05). After radical cystectomy, pathological stage distribution did not differ significantly (p > 0.05). The PDR was 74.07% (20/27) in the NACRT group and 87.50% (28/32) in the NACRT + PD-1 group (p=0.187). The PCRR increased from 44.44% (12/27) with NACRT alone to 71.88% (23/32) with PD-1 addition (p=0.033). Toripalimab and tislelizumab achieved comparable PDRs (83.33% . 92.86%, p=0.613) and PCRRs (66.67% . 78.57%, p=0.694). No grade ≥4 AEs or treatment-related deaths occurred, and AE frequencies were similar between groups (all p > 0.05).

[CONCLUSION] NACRT combined with PD-1 blockade significantly improved PCRR without increasing toxicity in patients with MIBC. These findings support conducting a prospective single-arm phase II multicenter trial to confirm potential long-term survival benefits.