Neoadjuvant chemotherapy followed by surgery significantly improves outcomes for potentially resectable intrahepatic cholangiocarcinoma compared to upfront surgery.

• Median overall survival is 52.9 months with neoadjuvant therapy versus 37.0 months with upfront surgery.
• Recurrence is delayed (34.6 months vs. 24.4 months) and fewer patients are at risk of death (46.4% vs. 75.3%).
• Five-year survival rates are substantially higher (45.7% vs. 32.5%), indicating a need to revise treatment guidelines.

Consider neoadjuvant chemotherapy especially for patients at high risk of recurrence to enhance surgical outcomes.