Neoadjuvant Sintilimab with Gemcitabine and Cisplatin for Muscle-Invasive Bladder Cancer

Radical cystectomy (RC) is the standard treatment for patients with Muscle-invasive bladder cancer (MIBC). However, it carries significant morbidity, perioperative mortality of about 5%, and negative impacts on quality of life. A recent phase 2 trial evaluated the efficacy and safety of neoadjuvant sintilimab (a PD-1 inhibitor) combined with gemcitabine-cisplatin (GP) in MIBC patients and assessed the feasibility of subsequent bladder-sparing surgery.

The study included 55 patients with histopathologically confirmed urothelial carcinoma (T2-4a, N≤1, M0) between May 2020 and May 2023. The treatment regimen consisted of sintilimab 200 mg on day 8, in combination with gemcitabine 1,000 mg/m² and cisplatin 35 mg/m² on days 1 and 8, repeated every 21 days for four cycles. Among the 46 evaluable patients (median age 62 years, 91.3% male), 39.1% had clinical T3-T4a disease. Most patients (73.9%) completed all four neoadjuvant cycles.

Of the 42 patients who underwent surgery, 16 (38.0%) achieved pathologic complete response (pCR), and 33 (78.6%) achieved downstaging to non-muscle-invasive disease (pT<2). All patients achieved R0 resection. The pT<2 rate was higher in patients receiving 4 cycles (76.7%) versus 2 cycles (57.1%) of therapy. Despite high baseline T3-T4a disease (39.1%), bladder preservation was achieved in 31 patients (67.4%), including transurethral resection (22 patients), partial cystectomy (5 patients), and surveillance without surgery (4 patients).

With a median follow-up of 25.3 months, the 1-year event-free survival rate was 91.3%. Although there was a trend toward higher recurrence in the bladder preservation group compared to radical cystectomy, the difference was not statistically significant (p=0.337). All patients experienced adverse events, with grade ≥3 events in 45.8%. The most common grade 3-4 treatment-related adverse event was neutropenia (27.3%). No severe immune-related adverse events occurred. Quality of life assessments showed that bladder preservation patients had significantly better outcomes across multiple domains at 1-year follow-up compared to patients who had RC.

This study highlights the promise of chemotherapy-immunotherapy combination for enabling bladder preservation in select patients.

Written by: Bishoy M. Faltas, MD, Chief Research Officer, Englander Institute for Precision Medicine, Gellert Family - John P. Leonard, MD, Research Scholar, Associate Professor of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York- Presbyterian Hospital, NY

References:

Tong Z, Fu G, Zhou F, Liu X, Xue X, Zhang H, Wang Y, Zhu X, Gao Y, Liu L, Bao X, Zheng Y, Fang W, Zhao P, Jin B. Neoadjuvant Sintilimab Combined with Gemcitabine and Cisplatin (GP) for Muscle-Invasive Bladder Cancer (MIBC) Patients Followed by Selective Bladder Sparing Surgery: A Phase 2 Trial. Cancer Res Treat. 2025;doi:10.4143/crt.2025.214.

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