Abstract

Purpose
To evaluate the safety and efficacy of GP regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for MIBC patients and the feasibility of the following selective bladder sparing surgery.
Materials and Methods
Patients with histopathological confirmed urothelial carcinoma without distant metastases (T2-4a, N≤1, M0, AJCC 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT<2 rate, R0 resection rate, event free survival and safety.
Results
From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. 33 patients (78.6%) achieved pT<2. With a median follow-up of 15.7 months, the 1-year EFS was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients TURBT, 5 patients partial cystectomy and 4 surveillances) rate was achieved (67.4%). The most common grade ≥3 TRAEs was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related AEs.
Conclusion
Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT<2 rate and triggering the emerging roles for the MDT decision-making for bladder sparing surgery.

• Keywords: Urinary bladder neoplasms, Neoadjuvant therapy, Immunotherapy