**3.1 Systemic treatment**

In general, extra-hepatic metastasis is regarded as an advanced systemic disease and therefore, only systemic chemotherapy or supportive treatment will be offered only. Unfortunately, the response rate of HCC to systemic chemotherapy such as adriamycin is very low and the results were mostly disappointing (Simonetti et al., 1997).

With better understanding of the mechanism of hepatocarcinogenesis, effective molecularly targeted agents, such as sorafenib, have been emerged and improved survival benefits have been demonstrated in large, placebo-controlled phase III trials in Europe and Asia for patients with advanced HCC (Cheng et al., 2009; Llovet et al., 2008). While some may criticize that the benefit gained from sorafenib over placebo in patients with extra-hepatic metastasis from HCC was marginal only, the extra months gain may well be extremely valuable to patients.
