Three-Tiered Nodal Staging System Improves Prognostic Utility for Intrahepatic Cholangiocarcinoma

Area of Science:

• Oncology
• Surgical Pathology
• Cancer Staging

Background:

• Current American Joint Committee on Cancer staging for intrahepatic cholangiocarcinoma (iCCA) uses a binary nodal classification.
• The prognostic value of this binary system and its association with chemotherapy benefit require further evaluation.

Purpose of the Study:

• To evaluate a proposed three-tier nodal classification for resected intrahepatic cholangiocarcinoma (iCCA).
• To assess the association of this three-tier system with overall survival and chemotherapy benefit.

Main Methods:

• Retrospective analysis of 6365 patients with resected iCCA from the National Cancer Database.
• Nodal status reclassified into N0 (no positive nodes), N1 (1-2 positive nodes), and N2 (≥3 positive nodes).
• Overall survival compared using Kaplan-Meier curves and multivariable Cox models with propensity score matching.

Main Results:

• Median overall survival decreased stepwise across N0 (55.3 months), N1 (24.5 months), and N2 (19.0 months) stages (p < 0.001).
• N1 and N2 stages were independently associated with worse survival (HR 2.01 and 2.59, respectively) compared to N0.
• The three-tier system showed superior model performance over binary staging; adjuvant chemotherapy demonstrated greater survival benefit in node-positive patients.

Conclusions:

• A three-tier nodal classification offers superior prognostic stratification for resected iCCA compared to the current binary system.
• Node positivity is linked to a substantial survival change, indicating its utility in guiding systemic treatment decisions for iCCA.