Optimizing the management of intermediate-stage hepatocellular carcinoma: Current trends and prospects

Abstract

Hepatocellular carcinoma (HCC) is usually accompanied by chronic liver damage, which sometimes influences the selection of HCC treatment. The Barcelona Clinic Liver Cancer (BCLC) staging system, which was first introduced in 1999, is the most commonly used worldwide. Although the intermediate-stage (BCLC stage B) includes the largest number and heterogeneous HCC patients, the recommended treatment option is transarterial chemoembolization (TACE) only. However, recent progress in radical treatments such as hepatic resection, liver transplantation, radiation therapy, and percutaneous therapy has made it possible to treat selected patients with BCLC stage B HCC. Radical treatments are expected to prolong survival time. To-date, TACE has also progressed. In addition to conventional TACE, balloon-occluded TACE and drug-eluting beads TACE are available. These new modalities of TACE will improve therapeutic efficacy and reduce adverse events. One of the most serious concerns of TACE is that repeated TACE reduces the treatment effect and induces liver function impairment. The decision on when TACE should be interrupted is complex. Many molecular targeted agents are now available, and immune checkpoint inhibitors will soon be available for HCC patients with Child-Pugh class A worldwide. Under these circumstances, in patients with TACE unsuitability, switching to molecular targeted agents before deterioration of liver function might improve the prognosis compared to repeated TACE. We should pay attention to stop TACE in TACE-unsuitable HCC patients as it can induce the deterioration of liver function.

Keywords: BCLC; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Immune checkpoint inhibitors; Molecular targeted therapy.

Figure 1.

Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy. Modified from Forner et al. [8] with permission from Elsevier. HCC, hepatocellular carcinoma; ECOG, Eastern Cooperative Oncology Group; PS, performance status; BSC, best supportive care. ^*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.

Grade of response to cTACE in BCLC stage B HCC. Reprinted from Bruix et al. [45] with permission from S. Karger AG. RFA, radiofrequency ablation; cTACE, conventional transarterial chemoembolization; DEB-TACE, drug-eluting beads transarterial chemoembolization; IO, immune-oncology; TKI, tyrosine kinase inhibitor; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma.

Figure 3.

Potential therapeutic options in BCLC stage B. BCLC, Barcelona Clinic Liver Cancer; TACE, transarterial chemoembolization; MTA, molecular targeted agent; ICI, immune checkpoint inhibitor; TARE, transarterial radioembolization.

Figure 4.

Influence of VEGF on tumor immunity. MHC, major histocompatibility complex; TCR, T-cell receptor; DC, dendritic cell; CTLA-4, cytotoxic T-lymphocyte antigen 4; VEGF, vascular endothelial growth factor; Treg, regulatory T cell; MDSC, myeloid-derived suppressor cell; IL, interleukin; HCC, hepatocellular carcinoma; TAM, tumor associated macrophage; PD-1, programmed death-1; PD-L1, programmed death ligand 1.