A cohort study on efficacy and safety of treatment modalities for resectable hepatocellular carcinoma with extrahepatic metastasis

Abstract

Background and aims This study compared survival outcomes, prognostic factors, and safety between hepatectomy and interventional and systemic therapy among patients with hepatocellular carcinoma (HCC) with resectable intrahepatic lesions and extrahepatic metastasis. Methods A total of 490 patients were enrolled between January 2014 and December 2024 and were divided into two groups based on treatment modality: hepatectomy group (n = 152) and interventional and systemic therapy group (n = 338). Overall survival (OS) and event-free survival (EFS) were analyzed via the Kaplan–Meier method and compared using the log-rank test. Propensity score matching (PSM) was applied to reduce baseline differences between the two groups. Prognostic factors were evaluated using univariate and multivariate Cox proportional hazards regression analyses. Adverse events were evaluated using the Clavien–Dindo classification and Common Terminology Criteria for Adverse Events (version 5.0). Results Hepatectomy yielded superior 1-, 3-, and 5-year OS rates (58.4%, 30.5%, and 26.0%, respectively, vs. 48.6%, 20.7%, and 11.9%, respectively) and longer median OS (17 vs. 12 months), and this benefit persisted after PSM. However, the EFS benefit was lost after PSM. Sensitivity analysis excluding “other” metastases (adjacent organ invasion) attenuated the OS benefit but preserved the EFS benefit. Subgroup analyses highlighted treatment effect heterogeneity by metastasis site, age, prealbumin level, and portal vein tumor thrombosis (PVTT). Multivariate analysis identified sex (male), prealbumin ≥ 200 mg/L, and PVTT as independent predictors of OS. Conclusions Hepatectomy might provide a survival benefit over interventional and systemic therapy in carefully selected patients with resectable HCC and extrahepatic metastasis, particularly those with lung-only metastasis, preserved liver function, and no PVTT.