Neoadjuvant therapy reduces node positivity but does not confer survival benefit versus up-front resection for resectable intrahepatic cholangiocarcinoma: A propensity-matched analysis.

Background: Neoadjuvant systemic therapy (NAST) is a treatment option for intrahepatic cholangiocarcinoma (iCCA), though its impact on short-term oncologic outcomes and long-term survival remains relatively unknown.

Methods: The National Cancer Database (NCDB) between 2004 and 2019 was queried for patients with reportedly resectable (Stage I-IIIB) iCCA who received curative-intent resection with lymphadenectomy. Propensity matching was performed between groups based on the use of NAST and groups were compared for overall survival (OS) and oncologic outcomes, including nodal harvest, rate of node positivity, rate of positive margins, and administration of adjuvant therapy.

Results: Two thousand and five hundred ninety-six patients met inclusion criteria; 364 (14%) received NAST versus 1763 (68%) up-front resection. After matching, 332 pairs of patients were matched between NAST and no NAST. Patients receiving NAST had a greater nodal harvest (OR = 1.26 [1.09-1.88]; p < 0.001) and a lower rate of node positivity (OR = 0.67 [0.49-0.63]; p < 0.001). Patients without NAST were more likely to complete adjuvant systemic therapy (OR = 0.45 [0.33-0.62]; p < 0.001). However, patients receiving NAST had no OS benefit after resection compared to those who did not receive NAST (median OS 48.3 ± 5.3 vs. 38.8 ± 3.7 months; p = 0.160). Node-positive disease (OR = 2.10 [1.78-2.45]; p < 0.001) conferred the greatest risk for reduced OS followed by positive-margin resection (OR = 1.42 [1.21-1.47]; p < 0.001) and increasing T-stage (OR = 1.34 [1.21-1.47]; p < 0.001).

Conclusion: NAST for iCCA was associated with improved quality of oncologic resection but did not confer an OS benefit versus up-front resection.