From the Guidelines
Neoadjuvant chemotherapy can be considered in patients with resectable and borderline resectable intrahepatic cholangiocarcinoma, particularly in those with technically challenging disease, to potentially improve resectability rates and overall survival. According to the EASL-ILCA clinical practice guidelines on the management of intrahepatic cholangiocarcinoma 1, neoadjuvant systemic chemotherapy may induce a tumor response and render some patients operable after treatment. The guidelines suggest that decision-making currently relies on retrospective series of systemic chemotherapy, propensity score-matched analyses, and studies of intrahepatic arterial infusion and systemic chemotherapy.
The largest retrospective series, a French study, found that of 186 patients with initially unresectable disease, 74 received chemotherapy, and 39 of those 74 (53%) underwent resection following chemotherapy, with a median overall survival (OS) of 24.1 months, similar to that observed in patients who had upfront resectable disease (median OS: 25.7 months) 1. This suggests that neoadjuvant chemotherapy may be beneficial in improving outcomes for patients with resectable and borderline resectable intrahepatic cholangiocarcinoma.
Key considerations for neoadjuvant chemotherapy in this setting include:
- Tumor size and vascular involvement
- Patient performance status
- Radiographic assessment after 2-3 cycles to determine response and surgical timing
- Multidisciplinary tumor board discussions to individualize treatment decisions
- Potential benefits of addressing micrometastatic disease early, assessing tumor biology through treatment response, and improving R0 resection rates.
While definitive evidence from large randomized controlled trials is still lacking, the available data suggest that neoadjuvant chemotherapy can be a valuable treatment option for patients with resectable and borderline resectable intrahepatic cholangiocarcinoma, and treatment decisions should be made on a case-by-case basis, taking into account the latest evidence and guidelines 1.
From the Research
Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Intrahepatic Cholangiocarcinoma
- The use of neoadjuvant chemotherapy in resectable and borderline resectable intrahepatic cholangiocarcinoma has been explored in several studies 2, 3, 4, 5.
- A phase II feasibility trial (NEO-GAP) evaluated the use of neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel in patients with resectable, high-risk intrahepatic cholangiocarcinoma, demonstrating a disease control rate of 90% and a completion rate of 73% for both preoperative chemotherapy and surgical resection 2.
- Another study, the GAIN trial, is a phase III randomized controlled trial investigating the use of neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone in patients with incidentally detected gallbladder carcinoma or resectable/borderline resectable cholangiocarcinoma 3.
- A review of neoadjuvant therapy for cholangiocarcinoma highlighted the potential benefits of this approach, including improved local and distant control, achievement of R0 resection, and prevention of distant metastasis 4.
- The use of neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma has also been reviewed, with recent advances in liver-directed therapies, chemotherapy regimens, and targeted therapies generating increasing interest in this area 5.
Efficacy and Safety
- The NEO-GAP trial demonstrated that neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma, with no adverse impact on perioperative outcomes 2.
- The GAIN trial aims to investigate the efficacy and safety of neoadjuvant chemotherapy with gemcitabine plus cisplatin in patients with resectable/borderline resectable cholangiocarcinoma, with primary endpoints including overall survival and secondary endpoints including progression-free survival, R0-resection rate, toxicity, perioperative morbidity, and quality of life 3.
Future Directions
- Ongoing and recruiting trials, such as the GAIN trial, will provide further insight into the efficacy and safety of neoadjuvant chemotherapy in resectable and borderline resectable intrahepatic cholangiocarcinoma 3, 4.
- The use of triplet regimens, including gemcitabine, cisplatin, and immune checkpoint inhibitors, may change the concept of resectability in biliary tract cancers, including intrahepatic cholangiocarcinoma 6.