Treatment strategies for locally advanced hepatocellular carcinoma

Abstract

Liver cancer ranks fifth in incidence and fourth in overall cancer-related mortality, with approximately 854,000 new cases and 810,000 deaths per year worldwide. Hepatocellular carcinoma (HCC) accounts for 90% of these cases, and, over time, both the incidence and mortality of this cancer have been rising in many regions. Several staging systems are used to assess the extent of primary tumor, presence of metastasis, and underlying liver disease, and thereby aid in the definition of treatment strategies and prognosis for these patients. The consequence of this heterogeneity in HCC staging is that no consensual definition of advanced disease exists, and there is still ongoing debate on the optimal treatment for these patients. Patients with advanced tumors can be candidates for multiple therapies, ranging from potentially curative options such as transplantation and resection-to locoregional and systemic treatments; these should be evaluated on an individual basis by a multidisciplinary team. This paper provides an overview of treatment options for advanced stage HCC, based on a review of the latest relevant literature and the personal experience of the authors.

Keywords: Cirrhosis; hepatectomy; hepatocellular carcinoma (HCC); liver neoplasms; liver transplantation.

Figure 1

Barcelona clinic liver cancer (BCLC) staging and treatment strategy. *, Patients with end-stage cirrhosis due to heavily impaired liver function (Child-Pugh stage C or earlier stages with predictors of poor prognosis or high a MELD score) should be considered for liver transplantation. In these patients, hepatocellular carcinoma might become a contraindication if it exceeds enlistment criteria. ^†, currently, sorafenib followed by regorafenib has been shown to be effective. Lenvatinib has been shown to be non-inferior to sorafenib, but no second-line option after lenvatinib has been explored.

Figure 2

Hong Kong Liver Cancer (HKLC) prognostic classification. Early tumor: 5 cm, up to three tumor nodules and no intrahepatic venous invasion; intermediate tumor: (I) 5 cm, either >3 tumor nodules with intrahepatic venous invasion or (II) >5 cm, three tumor nodules and no intrahepatic venous invasion; locally advanced tumor: (I) 5 cm, >3 tumor nodules and intrahepatic venous invasion, or (II) >5 cm, >3 tumor nodules and/or intrahepatic venous invasion, or (III) diffuse tumor (10). EVM, extrahepatic vascular invasion/metastasis.

Figure 3

Living-donor liver transplantation (LDLT). Right lobe (A) with MHV graft (B).

Figure 4

Final appearance after associated liver partition and portal vein ligation for staged hepatectomy (ALPPS).