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Surgery vs. non-surgery for advanced cholangiocarcinoma post-conversion therapy with PD-1/PD-L1 inhibitors plus TKIs
Zengpeng Sun1, Yutao Wang1, Xu Chen1
1Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, China.
Frontiers in Immunology
|February 16, 2026
Summary
Surgical resection after PD-1/PD-L1 inhibitors plus TKIs significantly improves overall survival (OS) and progression-free survival (PFS) in initially unresectable cholangiocarcinoma (CCA) patients. Conversion surgery is safe and feasible, offering better outcomes than non-surgical therapy.
Area of Science:
- Hepatobiliary Malignancies
- Gastrointestinal Oncology
- Translational Cancer Research
Background:
- Cholangiocarcinoma (CCA) is a challenging cancer, often diagnosed at unresectable stages.
- Neoadjuvant immunotherapy (PD-1/PD-L1 inhibitors) combined with tyrosine kinase inhibitors (TKIs) shows promise for downstaging initially unresectable CCA.
- The role of conversion surgery after neoadjuvant therapy in CCA remains an area of active investigation.
Purpose of the Study:
- To compare overall survival (OS) and progression-free survival (PFS) between surgical resection and non-surgical therapy.
- To evaluate the efficacy of conversion surgery in patients with initially unresectable CCA who became resectable after neoadjuvant treatment.
- To assess the safety and feasibility of surgical resection in this patient cohort.
Main Methods:
- Retrospective analysis of 47 patients with initially unresectable CCA treated between June 2020 and December 2024.
- Patients were divided into surgical resection (SR) and non-surgical resection (NR) groups based on post-conversion treatment.
- Comparison of OS, PFS, and recurrence-free survival (RFS) using Cox regression analysis.
Main Results:
- Surgical resection (SR) group (23 patients) showed significantly superior median OS (not reached vs. 28.5 months) and PFS (19 vs. 13.5 months) compared to the non-surgical resection (NR) group (24 patients).
- 1-, 2-, and 3-year OS rates were 95.7%, 68.5%, 68.5% for SR versus 91.7%, 51.4%, 17.6% for NR (P=0.026).
- 1-, 2-, and 3-year PFS rates were 87.0%, 40.2%, 25.2% for SR versus 61.6%, 12.4%, 12.4% for NR (P=0.025). R0 resection achieved in 91.3% of SR patients with no surgery-related mortality.
Conclusions:
- PD-1/PD-L1 inhibitors plus TKIs can effectively downstage initially unresectable CCA, enabling conversion surgery.
- Conversion surgery is a safe and feasible treatment option for selected CCA patients.
- Surgical treatment significantly improves OS and PFS compared to non-surgical management in this patient population.
