Which treatment modality should we choose for advanced hepatocellular carcinoma?

The definition of 'advanced' hepatocellular carcinoma (HCC) has been vague and included various stages. This term has sometimes meant 'multinodular/unresectable HCC', 'HCC with vas-cular invasion', or 'HCC with extra-hepatic spread'. Since the introduction of the Barcelona Clinic Liver Cancer (BCLC) stage in 1999, the term 'advanced HCC' has been defined as a symptomatic tumor and/or invasive tumoral pattern (vascular invasion/ extrahepatic spread). 1 Based on data suggesting limited efficacy of cytotoxic systemic chemotherapy and results from the SHARP trial, 2,3 sorafenib, a multi-kinase inhibitor, is now the only drug which has been shown to prolong the survival of patients with HCC with vascular invasion or metastasis. Transarterial chemoembolization (TACE) is the standard of care for patients with multinodular HCC. 4 Although there is not a standardized procedure with different embolic or chemotherapeutic agents, different arterial selectivity before embolization, or different schedules and indications for repeated sessions, 5 TACE has been shown to be effective in prolonging survival compared to supportive care in randomized controlled trials and meta-analyses. 5,6 However, the outcomes of TACE depend upon patient selection. In a randomized trial which recruited HCC patients with compensatory cirrhosis, good performance status, and large or multinodular HCC with neither portal vein invasion nor distant metastasis, the 2-year survival rate was 63% compared to 27% for the untreated control group (P=0.009). 7 In another randomized trial, inclusion of patients with symptoms or limited portal vein invasion resulted in a 2-year survival rate of 31%. 6 In a subgroup analysis, TACE offered no survival benefit in patients with portal vein invasion. In addition to high rates of tumor recurrence or progression after the procedure, TACE promotes vascular endothelial growth factor (VEGF) production and subsequent angiogenesis. Therefore, apart from adverse events, the suboptimal anti-cancer effects of TACE observed when treating HCC with portal vein invasion may increase the chance of intra-or extra-hepatic spread of HCC. Hepatic arterial infusional chemotherapy (HAIC) using low-or high-dose 5-FU and cisplatin for unresectable HCC has been established as a treatment option in Japan and several centers in South Korea. Despite several problems associated with HAIC such as subcutaneous port implantation and catheter placement, infection, and hepatic arterial occlusion with repeated therapies, promising HAIC anti-tumor effects without significant systemic adverse events have been reported in locally advanced HCC. 8,9 In a Japanese study, low doses of 5-FU (170 mg/m 2 on day 1-5) and low doses of cisplatin (7 mg/m …