Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis

Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.