Characteristics of “Very Early” Intrahepatic Cholangiocarcinoma Undergoing Liver Resection and Its Relationship With Carbohydrate Antigen 19‐9

Introduction The concept of “very early” ICC ( ≤ 2 cm, single tumor) has been introduced in the context of LT. Due to the limited number of patients in this subset, the characteristics and long‐term outcomes have been ill‐defined. We sought to assess long‐term outcomes of very early ICC patients undergoing liver resection using a large, multi‐institutional database. Methods Patients who underwent curative‐intent hepatectomy for ICC between 1993 and 2023 were identified from the International Intrahepatic Cholangiocarcinoma Study Group database. Multivariable Cox regression analysis was performed to identify the risk factors related to overall survival (OS) and recurrence‐free survival (RFS). Results Among 1868 ICC patients, 86 (4.6%) met the criteria for very early ICC. While patient and tumor characteristics were similar between very early and non‐very early ICC, 1‐, 3‐, and 5‐year OS among patients with very early ICC was 92.3% (IQR 86.6−98.4), 72.6% (IQR 62.7−84.1), and 58.0% (IQR 45.9−73.5), respectively, versus 80.8% (IQR 78.9−82.7), 51.0% (IQR 48.4−53.8), and 38.9% (IQR 36.1−41.9), respectively, among non‐very early ICC patients ( p < 0.01). On multivariable Cox regression analysis, elevated CA19‐9 levels were associated with worse OS (HR 3.05, IQR 1.28−7.30, p = 0.01) and RFS (HR 2.88, IQR 1.24−6.66, p = 0.01). Very early ICC patients with higher CA19‐9 level were more likely to have metastatic nodal disease (N1: ≥ 40 U/mL n = 11, 40.7%, vs. n = 3, 5.1%, p < 0.001), microvascular invasion ( ≥ 40 U/mL n = 10, 37.0%, vs. n = 4, 6.8%, p < 0.001), and major vascular invasion ( ≥ 40 U/mL n = 8, 29.6%, vs. n = 2, 3.4%, p < 0.01). Conclusions Very early ICC was associated with favorable long‐term outcomes; however, elevated CA19‐9 levels identified a subgroup with a much worse prognosis and more aggressive tumor features. CA19‐9 may help guide perioperative treatment decisions, including additional treatment after surgical interventions.