Impact of Intrahepatic Tumor Burden on Outcomes in Patients With Hepatocellular Carcinoma With Extrahepatic Metastases Treated With Atezolizumab Plus Bevacizumab

BACKGROUND & AIMS: Systemic therapy is the standard care for patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. However, the relative prognostic importance of the intrahepatic tumor burden versus the extent of extrahepatic disease in the era of immune checkpoint inhibitor-based therapy remains unclear. This study aimed to clarify the prognostic impact of intrahepatic tumor burden in patients with metastatic HCC treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS: We conducted a multicenter retrospective study of patients with HCC and extrahepatic metastases who received first-line Atez/Bev therapy. The intrahepatic tumor burden was assessed using established radiologic parameters, including tumor size, number, and vascular invasion, and the patients were stratified according to the intrahepatic disease severity. Overall survival (OS) was defined as the primary endpoint. Survival analyses were carried out using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Overall, 306 patients were included in the study. During a median follow-up of 13.5 months, the OS differed markedly according to the intrahepatic tumor burden and macrovascular invasion. The median OS was 17.8 months in the mild MVI group, 12.2 months in the severe MVI group, 29.8 months in the UT7 in group, and 15.2 months in the UT7 out group (p < 0.001). In multivariate analysis, the intrahepatic tumor burden remained an independent predictor of OS, whereas the extent and number of extrahepatic metastatic sites were not significantly associated with prognosis. CONCLUSIONS: In metastatic HCC treated with atezolizumab plus bevacizumab, intrahepatic tumor burden was associated with overall survival and may be useful for risk stratification and treatment optimization.