In resectable biliary tract cancer, clinical node positivity or CA19-9 ≥200 U/mL flagged early-recurrence risk; neoadjuvant chemotherapy was associated with better survival in this high-risk group.

• Among 171 high-risk patients, NAC (49 patients) was associated with improved overall survival (HR 0.57) and recurrence-free survival (HR 0.61) versus upfront surgery.
• Recurrence within one year was linked to inability to continue systemic treatment for at least three months.

This retrospective comparison supports considering NAC for high-risk patients, but cannot establish that it caused the survival difference.