Biologically Refined Oncological Resectability for Hepatocellular Carcinoma

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.

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.

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).

Refinement using AFP and DCP identified a biologically aggressive subset within the R group and may improve early recurrence prediction.