Biologically Refined Oncological Resectability for Hepatocellular Carcinoma

BACKGROUND/PURPOSE: Oncological resectability criteria for hepatocellular carcinoma (HCC) have been proposed to guide multidisciplinary treatment, but their validation remains limited. Incorporating biological factors may improve prognostic stratification and identification of borderline-resectable HCC. METHODS: Patients undergoing initial hepatectomy for HCC (2009-2022) were classified as resectable (R), borderline-resectable (BR)1, or BR2. Stratification of overall survival (OS) and recurrence-free survival (RFS) was compared with the BCLC staging system. R-group patients with alpha-fetoprotein (AFP) ≥ 400 ng/mL and des-gamma-carboxy prothrombin (DCP) ≥ 400 mAU/mL were subclassified as biological-BR. RESULTS: Among 391 patients (R: 330; BR1: 23; BR2: 38), survival stratification was comparable to the BCLC classification. Twenty-six R-group patients were reclassified as biological-BR, with higher microvascular invasion rates (42.3%) and 5 year OS and 3 year RFS similar to BR1 patients (54.9% vs. 51.3%, p = 0.457; 38.1% vs. 25.0%, p = 0.954). Combining Biological BR with BR1 significantly improved time-dependent prediction of 6 month recurrence, with an area under the receiver operating characteristic curve (Refined: 0.803; Original: 0.658, p ≤ 0.001, BCLC: 0.608, p ≤ 0.001) and net reclassification improvement (0.220 vs. Original; 0.446 vs. BCLC). CONCLUSIONS: Refinement using AFP and DCP identified a biologically aggressive subset within the R group and may improve early recurrence prediction.