Published online Jun 28, 2017. doi: 10.4254/wjh.v9.i18.797
Systemic treatment of hepatocellular carcinoma: Past, present and future
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Abstract
Hepatocellular carcinoma (HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to hepatitis C. Although hepatitis therapies have evolved and the HCC screening has increased in several areas, 40% present with advanced disease which is only amenable for palliative systemic treatment. HCC continues posing a challenge, in part due to the inherent chemoresistance of this neoplasia, the pharmacologic challenges due to an ill liver, difficulty in assessing radiological responses accurately, etc. Traditional chemotherapy have shown some responses without clear survival benefit, however, sorafenib demonstrated advantages in survival in advanced HCC when liver function is kept and recently immunotherapy seems to be a promising approach for some patients. This article will briefly expose the most relevant systemic treatment modalities to offer a general view from the past to the future.
Core tip: The incidence of hepatocellular carcinoma (HCC) is rising in Western countries due to hepatitis C. Unfortunately, 40% of patients present with advanced disease which is only amenable for palliative systemic treatment. The development of effective therapies for HCC is a challenge, due partly to its inherent chemoresistance, the pharmacologic challenges due to an ill liver, etc. Although some responses to traditional chemotherapy have been reported, the multikinase inhibitor sorafenib has shown survival benefit in advanced HCC with preserved liver function. Recently immunotherapy seems to be a promising approach for some patients.
INTRODUCTION
Hepatocellular carcinoma (HCC) is a hepatic neoplasia that occupies the second place as cause of cancer related deaths[1]. It appears most frequently in a liver with chronic injury and cirrhosis[2] and it is usually diagnosed as an advanced stage with a poor median survival rate (6-20 mo)[3]. Its incidence varies depending on geographical zones and races.
This is mainly related to differences in incidences of hepatitis B and C. The highest rates are seen in Asia (where hepatitis B incidence is very high) and Africa, though increasing in developed areas due to hepatitis C[4]. Other risk factors include steatohepatitis, alcoholic liver disease, aflatoxins and hemochromatosis.
Unfortunately 40% of diagnosis will present with an advanced disease with the only options of systemic therapy in most of them[5]. HCC nowadays continues to pose a significant challenge to the therapy, in part due to poor chemosensitivity (expression of drug resistance genes) and the liver dysfunction which hinders the delivery of these drugs. Moreover, cirrhosis will have an impact on the drug distribution volumes[6].
Although newer treatments have appeared, the survival rates of advanced HCC patients have not yet significantly improved.
HCC is an aggressive tumour whose treatment possibilities will depend on the phase of the tumour, the liver functionality and patient’s performance status. There are several staging systems available[7-9] but no consensus on which to use. The Child-Pugh system will assess the patient’s hepatic reserve and liver function. Other staging systems, such as Barcelona Clinic Liver Cancer, will consider tumour phase, performance status, hepatic status, symptoms, etc. This system may provide the link between disease and treatment strategies. In very early/early stages, curative treatment (liver surgery or hepatic transplantation) and locoregional treatments (such as radiofrequency ablation), have better survival benefits.
Intermediate stage is very heterogeneous and transarterial chemoembolization/radioembolization are the main options if preserved hepatic function (Child-Pugh A) and performance status 0.
Advanced cases have got a short prognosis. For these patients, systemic palliative therapies might be considered.
This article will briefly expose the most relevant systemic treatment modalities to offer a general view from the past to the future.
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