Early Recurrence Limits Post-recurrence Therapy in Biliary Tract Cancer: A Rationale for Neoadjuvant Chemotherapy

The optimal treatment strategy for resectable biliary tract cancer (BTC) remains controversial, particularly in patients at high risk of early recurrence. We aimed to identify preoperative risk factors associated with impaired feasibility of post-recurrence treatment and to evaluate the impact of neoadjuvant chemotherapy (NAC) in high-risk patients.

We retrospectively analyzed patients with BTC who underwent upfront surgery (n = 323). Risk factors for intolerance (inability to continue systemic therapy for ≥ 3 months) after recurrence were evaluated, and high-risk patients were defined based on preoperative factors. In a separate cohort of 171 high-risk patients, outcomes were compared between patients who received NAC (n = 49) and those who underwent upfront surgery.

In the cohort of upfront surgery, clinical lymph node positivity (HR 1.96, P < 0.001) and elevated carbohydrate antigen 19-9 (CA19-9) levels (≥ 200 U/mL; HR 1.84, P < 0.001) were independent risk factors for recurrence-free survival (RFS). Among patients who developed recurrence, recurrence within 1 year was independently associated with intolerance after recurrence (OR 0.37, P = 0.003). Clinical lymph node positivity and/or elevated CA19-9 levels were independent risk factors for recurrence within 1 year (OR 3.27, P = 0.027). In the high-risk cohort, NAC was associated with significantly improved overall survival (OS) and RFS compared with upfront surgery (OS: HR 0.57, P = 0.022; RFS: HR 0.61, P = 0.016).

Patients with resectable BTC with elevated CA19-9 or clinical lymph node positivity are at high risk of early recurrence and limited treatment feasibility after recurrence. NAC may improve outcomes in this population by delaying recurrence.