Novel implications in the treatment of hepatocellular carcinoma

Abstract

Worldwide hepatocellular carcinoma remains one of the leading causes of cancer-related death, associated with a poor prognosis due to late diagnosis in the majority of cases. Physicians at care are frequently confronted with patients who are ineligible for curative treatment such as liver resection, transplantation or radiofrequency ablation. Besides established palliative locoregional therapies, such as ablation or chemoembolization, new treatment options, such as microwave ablation, drug-eluting bead transarterial chemoembolization or selective internal radiation therapy, are emerging; however, data from randomized controlled trials are still lacking. In order to achieve optimal tumor control, patients should receive tailored treatment concepts, considering their tumor burden, liver function and performance status, instead of strictly assigning patients to treatment modalities following algorithms that may be partly very restrictive. Palliative locoregional pretreatment might facilitate downstaging to ensure later curative resection or transplantation. In addition, the combined utilization of different locoregional treatment options or systemic co-treatment has been the subject of several trials. In cases where local tumor control cannot be achieved, or in the scenario of extrahepatic spread, sorafenib remains the only approved systemic therapy option. Alternative targeted therapies, such as immune checkpoint inhibitors have shown encouraging preliminary results, while data from phase III studies are pending.

Keywords: Hepatocellular carcinoma; individualized treatment concept; liver surgery; locoregional therapy; systemic therapy.

Figure 1

Hepatocellular carcinoma (HCC) epidemiology in Europe. Prospectively, because of hepatitis B vaccination programs and new highly effective anti-HCV therapies the incidence of HCC in the context of viral hepatitis will gradually decrease. In contrast, the global prevalence of the metabolic syndrome, encompassing hyperlipidemia, type-2 diabetes, arterial hypertension and obesity, will result in a concomitant strong increase in its hepatic equivalent, non-alcoholic fatty liver disease (NAFLD), which culminates in non-alcoholic steatohepatitis (NASH). This persistent hepatic inflammation is a prerequisite for HCC development, even in the absence of liver cirrhosis; therefore, the worldwide incidence of HCC is predicted to increase despite the improved prevention and treatment of viral hepatitis Art. HTN, arterial hypertension

Figure 2

BCLC staging system with hepatocellular carcinoma (HCC) treatment recommendation by the authors. Patients in very early and early HCC stages should receive either ablation, resection or liver transplantation. Resection should be offered only to those patients in Child-Pugh A condition in the absence of portal hypertension, otherwise liver transplantation should be offered, if the Milan criteria are fulfilled. Radiofrequency (RFA) or microwave (MWA) ablation should be restricted solely to lesions ≤2 cm in size. During intermediate-stage disease, TACE should be performed. In cases where TACE is technically infeasible, SIRT can be offered. In advanced stages, SIRT can be offered, if patients have no prognostically relevant tumor burden (*Pulmonary filiae ≤1 cm, lymphonodular filiae ≤2 cm), otherwise systemic therapy with sorafenib is indicated until clinical progression or intolerable toxicity. In this case, second-line systemic therapy trials should be offered to patients. During terminal stage disease, patients should be offered best supportive care.