An exploratory study of clostridium butyricum combined with neoadjuvant chemoimmunotherapy in urothelial carcinoma.

4585 Background: Neoadjuvant chemoimmunotherapy using gemcitabine, cisplatin, and anti-PD1 has shown survival benefits for advanced bladder cancer patients, though response rates remain low. Recent studies highlight the role of clostridium butyricum in anti-tumor immunity, but its potential to enhance bladder cancer therapy is unexplored. Methods: This exploratory study (NCT06696742) involved patients with cT2-T4aN0M0 urothelial carcinoma at First Affiliated Hospital of Nanjing Medical University. Participants were randomized into two groups, one received with GC+anti-PD1 (gemcitabine 1.0 g/m 2 D1 and D8, cisplatin 70 mg/m 2 D2-4, and tislelizumab 200 mg D8 once every 21 days for 3-4 cycles), and the other received the same regimen plus Clostridium butyricum tablets (1-2 tablets, three times a day). Primary observations were pathological complete response (pCR, ypT0) and pathological down-staging ( < ypT2), the second observations included imaging assessment (RECIST 1.1) and safety. Results: In the combination group, 23 out of 30 patients completed treatment and underwent radical cystectomy, achieving a clinical complete response (CR) rate of 52.2% (12/23) and a partial response (PR) rate of 39.1% (9/23). Two patients (8.6%) showed stable disease (SD) and seven patients are still receiving treatment. Pathological downstaging was observed in 82.6% (19/23) of the patients, with 52.2% reaching ypT0 (12/23). In the control group, all 26 enrolled patients completed treatment and underwent radical cystectomy. The clinical CR rate was 30.7% (8/26), while the clinical PR rate was 42.3% (11/26). Six patients (23.1%) had stable disease, and 1 patient (3.8%) experienced disease progression (PD). Pathological downstaging occurred in 61.5% (16/26) of the patients, with 26.9% (7/26) achieving ypT0. The combination group demonstrated significantly higher rates of clinical CR+PR (P = 0.037) and pathological downstaging (P = 0.042) compared to the control group. There was no statistical difference between the two groups in terms of demographic characteristics. Conclusions: Combining neoadjuvant chemoimmunotherapy with Clostridium butyricum improves pathological and clinical response rates in cT2-T4aN0M0 urothelial carcinoma patients. Clinical trial information: NCT06696742 .