Real-World Single-Center Experience with Neoadjuvant Gemcitabine, Cisplatin, and Durvalumab in Borderline Resectable...

Gemcitabine, cisplatin, and durvalumab (GCD) have previously demonstrated favorable outcomes in advanced cholangiocarcinoma (CCA), leading to their approval as first-line therapy. This study evaluates the feasibility of GCD for borderline resectable CCA in the neoadjuvant setting.

Patients with borderline resectable CCA receiving neoadjuvant GCD between April 2022 and July 2024 were included. Treatment response (radiologic and pathologic), tolerability, postoperative morbidity, and survival outcomes were assessed.

Of 106 screened patients, 26 with anatomically or biologically borderline resectable disease received neoadjuvant GCD, with 12 proceeding to surgery (conversion rate: 46.2%). Extended resections were performed with extrahepatic bile duct resection (33.3%) and vascular reconstruction (25%). Tumor size reduction was observed in all resected patients, with RECIST showing stable disease in 83.3% and partial response in 16.7%. Pathologic response varied with no/minimal response in 41.7%, partial regression in 50.0%, and one complete response (8.3%). Postoperative morbidity (≥ grade III) was 50.0%, with 0% 90-day mortality. As of April 2025, 91.7% of resected patients were alive, although three developed recurrences (RFS: 5.5, 5.7, 6.8 months). Overall survival (OS) was significantly longer in resected versus non-resected patients (median OS: not reached versus 20.8 months, p = 0.047).

Our study indicates that neoadjuvant GCD is safe and well tolerated prior to extensive liver resection for borderline resectable CCA. A conversion rate of 46.2% suggests that GCD might be a promising treatment for patients with anatomically and biologically borderline resectable CCA. Heterogeneity of pathologic response rate highlights the need for biomarker-directed correlative studies in future investigations.