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

Current American Joint Committee on Cancer staging utilizes a binary classification for nodal staging of intrahepatic cholangiocarcinoma (iCCA). We evaluated a previously proposed three-tier nodal classification and its association with chemotherapy benefit using the National Cancer Database.

Patients with resected iCCA were identified from the National Cancer Database. Nodal status was reclassified as N0 (no positive nodes), N1 (one to two positive nodes), or N2 (three or more positive nodes). Overall survival was compared using Kaplan-Meier curves and multivariable Cox proportional hazards models with propensity score matching.

A total of 6365 patients met the inclusion criteria (N0: 4358 [68%]; N1: 1438 [23%]; N2: 569 [9%]). Median overall survival decreased in a stepwise fashion across proposed N stages: 55.3 months (N0), 24.5 months (N1), and 19.0 months (N2) (p < 0.001), with further separation seen in the cohort of patients with at least six harvested lymph nodes. On multivariable Cox analysis, both N1 (hazard ratio [HR] 2.01; 95% confidence interval [CI] 1.82-2.22) and N2 (HR 2.59; 95% CI 2.26-2.98) were independently associated with worse survival than N0. The proposed system demonstrated superior model performance than binary staging (delta Akaike information criterion 9, likelihood ratio test p < 0.001). Adjuvant chemotherapy was associated with a larger change in restricted mean survival time in node-positive patients (N1: 5.2 months; N2: 4.0 months) compared with node-negative patients (N0: 1.4 months).

Three-tier nodal classification provides superior prognostic stratification than binary American Joint Committee on Cancer staging in resected iCCA. Node positivity is associated with a larger absolute change in survival compared with node-negative patients, suggesting utility in systemic treatment selection.