Supplementary Material for: Low Tumor Burden Predicts Benefit from Transarterial Treatment in Hepatocellular Carcinoma with Extrahepatic Metastasis: A Nationwide Cohort Study

Background/Aims: In patients with hepatocellular carcinoma (HCC) and extrahepatic metastasis (EHM), intrahepatic disease control may remain clinically relevant in selected cases. This study aimed to compare survival outcomes between transarterial treatment (TAT) and systemic therapy (ST) as initial treatment. Methods: Data from the Korean Central Cancer Registry (2008–2020) were analyzed. TAT included chemoembolization, radioembolization, and hepatic arterial infusion chemotherapy. Systemic therapy consisted predominantly of tyrosine kinase inhibitors (>98%). Overall survival (OS) was the primary endpoint. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) adjusted for confounding. Results: Among 19,753 treatment-naïve HCC patients, 2,517 had EHM. Of these, 663 received TAT and 595 received ST as initial therapy. In the overall cohort, TAT was associated with significantly longer OS than ST (median OS: 6.7 vs. 3.7 months, P 10 cm. Multivariable analysis identified TAT, single-organ metastasis, AFP <400 ng/mL, and absence of PVTT as independent predictors of improved survival. TAT showed better survival in patients with low tumor burden, defined as intrahepatic tumor size <10 cm or metastasis confined to lymph nodes. In contrast, no significant difference was seen in those with high tumor burden, including large tumors and extrahepatic metastasis beyond lymph nodes. Conclusions: These findings suggest that TAT may be a viable initial treatment option for selected HCC patients with EHM, particularly those with lower tumor burden. Further comparative studies, especially with immunotherapy, are needed to define its optimal role in clinical practice.