Management of patients with hepatocellular carcinoma and extrahepatic metastasis

Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has recently been paradoxically increasing due to increased survival with effective locoregional therapies. The intrahepatic stage of the tumor is important for determining the risk of an extrahepatic lesion. Almost all patients with intrahepatic stage T(3-4), with or without EHM, die of progressive intrahepatic HCC but not due to EHM; thus, the majority of patients with HCC and EHM need to undergo concurrent treatment for intrahepatic HCC. There is no convincing evidence, to date, that systemic chemotherapy improves overall survival. Sorafenib is the first systemic agent that has demonstrated a significant survival benefit in patients with advanced HCC; however, the modest improvement of 3 months is far from satisfactory. Therefore, most hepatologists still rely on the conventional multidisciplinary approach to treat patients with EHM. The concept of the multidisciplinary treatment is the combination of locoregional therapies for both the intrahepatic HCC and symptomatic EHM when confined to a single organ. Targeted therapy may be considered for patients with advanced intrahepatic HCC and multiple EHM, however the potential efficacy of this approach requires confirmation. The outcome of ongoing clinical trials of the multidisciplinary approach, combining conventional locoregional therapy and targeted systemic therapy, is pending.