2375P - Neoadjuvant sintilimab combined with gemcitabine and cisplatin (GP) for muscle-invasive bladder cancer (MIBC) patients followed by selective bladder sparing surgery

Background

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.

Methods

Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N≤1, M0, AJCC 8th), and have adequate organ function will be enrolled. The therapeutic regimen were 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. Multi-disciplinary Treatment was conducted for surgical plan following neoadjuvant therapy. Radical cystectomy (RC) and bladder sparing strategy including partial cystectomy (PC) and TURBT and surveillance were fully discussed. Salvage surgery would be evaluated after recurrence. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were pT<2 rate, R0 resection rate, event free survival (EFS) and safety.

Results

From May 4, 2020 to Aug 10, 2022, 37 patients were enrolled. Notwithstanding the poor pathological situation of high T3-T4a proportion (n=14, 37.8%), a promising bladder preservation rate was achieved (73.0%, including 19 patients TURBT, 5 patients PC and 3 surveillance). Among the patients who underwent surgery (n=34), fourteen patients (41.2%) achieved pCR, twenty-seven patients (79%) achieved pT<2 (41% pT0, 9% pTa, 26% pT1, 3% pTis). All patients achieved R0 resection. With a median follow-up of 20.1 months, seven patients relapsed (bladder preservation vs. RC, 22.2% vs. 10%, p=0.321) and 1-year EFS was 89.1%. There was no significant difference between bladder-preserving and radical surgery subgroup to EFS (P=0.569). The most common grade ≥3 treatment-related adverse events (TRAEs) were neutropenia (n=8; 21.6%), which was related to chemotherapy. There were no Grade 3 immune-related AEs.

Conclusions

Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pCR rate and triggering the emerging roles for the MDT decision-making for bladder sparing surgery.

Clinical trial identification

ChiCTR2000032757.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.