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

Background: 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 And Methods: 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.

Results: 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).

Conclusions: 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.