ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Neoadjuvant chemoradiotherapy plus programmed cell death protein-1 blockade versus chemoradiotherapy alone for muscle-invasive bladder cancer: a real-world comparative study
Provisionally accepted
- The First Affiliated Hospital of Soochow University, Suzhou, China
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Background Muscle-invasive bladder cancer (MIBC) carries a high recurrence and mortality risk despite radical cystectomy. Neoadjuvant chemoradiotherapy (NACRT) has been explored as a bladder-preserving strategy in selected patients; however, in this study all patients underwent radical cystectomy after NACRT. Programmed cell death protein-1 (PD-1) inhibitors demonstrate antitumor activity in urothelial carcinoma. Combining NACRT with PD-1 blockade may improve tumor response, but its pathological benefits and short-term safety are not well defined. Methods We retrospectively analyzed 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 PD-1 inhibition with toripalimab (n = 18) or tislelizumab (n = 14). Chemotherapy comprised gemcitabine 1,000 mg/m² (days 1 and 8) plus cisplatin 70 mg/m² (days 2–3) every 21 days for ≥3 cycles. Pelvic intensity-modulated radiotherapy delivered 45 Gy in 25 fractions plus a 10 Gy bladder boost in five fractions. PD-1 antibodies were infused on day 8 each cycle. Primary endpoints were pathological downstaging rate (PDR, ≤ypT1/Tis/TaN0M0) and pathological complete response rate (pCRR, ypT0N0M0). Secondary endpoint was treatment-related adverse events (AEs) graded using CTCAE v5.0. Statistical comparisons employed χ², Fisher’s exact, or non-parametric tests (two-sided, α = 0.05). Results Baseline demographics and clinical characteristics were balanced between groups (all p > 0.05). Post-cystectomy pathological stage distribution did not differ significantly (p > 0.05). PDRs were 74.07% for NACRT alone and 87.50% for NACRT + PD-1 (p = 0.187). pCRRs increased significantly from 44.44% (12/27) with NACRT alone to 71.88% (23/32) with PD-1 addition (p = 0.033). Toripalimab and tislelizumab yielded similar PDRs (83.33% vs. 92.86%, p = 0.613) and pCRRs (66.67% vs. 78.57%, p = 0.694). No grade ≥4 AEs or treatment-related deaths occurred; AE incidence was comparable between groups (all p > 0.05). Conclusions NACRT combined with PD-1 blockade significantly improved pCRR without increasing toxicity in MIBC patients. These results support a prospective, multicenter phase II trial to assess whether enhanced pathological response translates into long-term survival benefits.
Keywords: Muscle-invasive bladder cancer, Neoadjuvant chemoradiotherapy, PD-1 inhibitor, Pathological complete response, Safety
Received: 23 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Zhang, Wang, Yu, Zhang, Ouyang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhiyu Zhang, abner_666@126.com
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