Neoadjuvant Therapy as a Selection Strategy for Curative Resection in High-Risk Intrahepatic Cholangiocarcinoma

Area of Science:

• Hepatobiliary Surgery
• Gastroenterology
• Medical Oncology

Background:

• High-risk features in intrahepatic cholangiocarcinoma (iCCA) correlate with poor prognosis.
• Neoadjuvant therapy (NAT) is increasingly used for high-risk iCCA to improve surgical outcomes.

Purpose of the Study:

• To evaluate the efficacy of neoadjuvant therapy (NAT) followed by resection in high-risk intrahepatic cholangiocarcinoma (iCCA) patients.
• To compare outcomes of NAT with upfront resection in high-risk and low-risk iCCA.

Main Methods:

• Retrospective analysis of 425 iCCA patients (Mayo Clinic) and 203 (MD Anderson Cancer Center).
• Patients categorized into high-risk iCCA with NAT and surgery, high-risk iCCA with upfront resection, low-risk iCCA with upfront resection, and high-risk iCCA with NAT without surgery.
• Outcomes assessed included overall survival (OS) and recurrence-free survival (RFS).

Main Results:

• NAT followed by resection in high-risk iCCA patients resulted in significantly longer OS (68.6 months) compared to upfront resection (34.9 months).
• Outcomes for NAT-treated patients who underwent resection were similar to low-risk iCCA patients (106.2 months).
• 44.2% of high-risk iCCA patients receiving NAT did not proceed to surgery due to progression or deterioration, with comparable OS to palliative care.

Conclusions:

• Neoadjuvant therapy followed by resection improves OS in select high-risk iCCA patients, indicating favorable tumor biology.
• A significant proportion of patients receiving NAT are unable to complete surgery, highlighting challenges in managing advanced iCCA.
• NAT may help select patients with better systemic therapy response for potentially curative surgery.