Synchronous two-nodule hepatocellular carcinoma without satellite nodules is associated with better survival outcomes compared with satellite-nodule hepatocellular carcinoma.

[AIMS] Multifocal hepatocellular carcinoma (HCC) is traditionally classified as multicentric occurrence (MO) or intrahepatic metastasis, a distinction that is difficult to apply in routine practice and not reflected in current staging systems. We aimed to assess the prognostic significance of different multifocal HCC patterns using simple, clinically applicable criteria.

[METHODS] We retrospectively analysed 153 patients with synchronous multifocal HCC who underwent surgical resection, including cases with two discrete nodules, more than two nodules and satellite nodules. 76 patients with solitary HCC served as controls. Histological classification based on Liver Cancer Study Group of Japan criteria was supplemented with promoter mutation analysis in selected cases. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan-Meier and Cox regression analyses.

[RESULTS] Histologic criteria alone failed to classify a substantial proportion of two-nodule HCCs. Although promoter analysis allowed partial reclassification, patients with undetermined two-nodule HCC had survival outcomes comparable to those classified as MO. In contrast, HCCs with satellite nodules showed significantly poorer OS and RFS. Multivariate analysis identified microvascular invasion and the presence of satellite nodules-but not two-nodule multifocality-as independent adverse prognostic factors. Notably, patients with two discrete nodules without satellite lesions did not show a statistically significant difference in OS or RFS compared with those with solitary HCC.

[CONCLUSIONS] Synchronous two-nodule HCC without satellite nodules represents a prognostically favourable subgroup distinct from satellite-nodule HCC. A simplified morphology-based stratification may better reflect clinical outcomes in multifocal HCC.