Breakthroughs in Hepatocellular Carcinoma Therapies

Abstract

Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are "TACE unsuitable" and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research.

Keywords: ablation; hepatocellular carcinoma; liver transplantation; molecular targeted therapy; resection; transarterial chemoembolization.

Figure 1.

Updated BCLC Staging and Treatment Algorithm. AFP, α-fetoprotein; ALBI, albumin-bilirubin; BSC, best supportive care; HCC, hepatocellular carcinoma; LT, liver transplantation; MELD, model for end-stage liver disease; PS, performance status; TACE, transarterial chemoembolization.

Figure 2.

Response-guided treatment strategy after TACE. LT, liver transplantation; TACE, transarterial chemoem bolization.

Figure 3.

Ongoing phase III trials. ABC, Atezolizumab plus Bevacizumab versus transarterial Chemoembolization; HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; TALENTACE, Tecentriq plus Avastin Liver Envision Tomorrow-TACE (A phase III, open-label, randomized study of on-demand TACE combined with atezolizumab plus bevacizumab [atezo/bev] or on-demand TACE alone in patients with untreated hepatocellular cacinoma).