Treatment of hepatocellular carcinoma

doi:10.1016/j.critrevonc.2006.06.001

Critical Reviews in Oncology/Hematology

Volume 60, Issue 2, November 2006, Pages 89-98

https://doi.org/10.1016/j.critrevonc.2006.06.001 Get rights and content

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related death. Despite therapeutic advances, the overall survival of patients with HCC has not significantly improved in the last two decades. In the majority of the cases there is underlying cirrhosis, so the prognosis of HCC depends on not only tumor stage but also liver function. There is not a widely accepted HCC staging system. In our group we have developed a new staging classification that stratifies HCC patients into four major categories and simultaneously links staging with treatment. Patients at an early stage are those who present with an asymptomatic single HCC with a maximum diameter of 5 cm or up to three nodules each less than 3 cm. They will benefit from curative therapies, including resection, liver transplantation (LT), and percutaneous ablation. Patients exceeding these limits, but who are free of cancer-related symptoms and vascular invasion or extrahepatic spread fit into the intermediate stage and may benefit from palliation with chemoembolization. The patients with mild cancer-related symptoms and/or vascular invasion or extrahepatic spread are included in the advanced stage. In this stage there is not effective therapy, and these patients may profit from new therapies in the setting of randomized controlled trials (RCTs). Finally, the patients with severe cancer-related symptoms or great tumor burden belong to the terminal stage and only benefit from symptomatic treatment.

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world [1]. It has gained clinical interest because of its growing worldwide incidence [2], secondary in part to an increased ability to diagnose the disease, but mostly due to the long-term consequences of chronic HCV infection. It is expected that the rise in the incidence of HCC in the United States will continue during the next two decades [3]. In the majority of the cases there is underlying cirrhosis, mainly caused by hepatitis B and C viruses. The HCC incidence rate in patients with HCV-related cirrhosis is 3.7 per 100 person years [4]. The current effective treatments available are only applicable in a relatively small proportion of early stages cases. When HCC presents with clinical symptoms, the tumor is usually advanced, and there are few therapeutic options. For these reasons, screening for HCC in patients affected with cirrhosis is appropriate. Nevertheless, there is no definitive evidence that surveillance improves patient survival. In addition, is not known which screening interval and how the available tools can be optimized. The present recommended surveillance policy is a biannual abdominal ultrasound in cirrhotics who would benefit from effective treatment if HCC were diagnosed [5].

Section snippets

Diagnosis

Once a hepatic nodule has been detected, the next step is to characterize and determine its nature. HCC has a specific vascular profile characterized by an exclusive arterial vascularization, that determines the importance of dynamic imaging techniques (contrast-enhanced US, CT, and MRI) in the diagnosis of HCC. The specific vascular profile of HCC provokes an intense contrast uptake during the early arterial phase after contrast administration followed by contrast washout during the

Prognosis

It is well known that cirrhosis underlies HCC in most patients and that liver function has a significant impact on prognosis, regardless of tumor burden. Accordingly, any proposal to stratify patients into different prognostic groups has to consider not only tumor stage but also liver function. Several staging systems have been proposed [7]. We developed years ago the Barcelona Clinic Liver Cancer (BCLC) system, which takes into account factors such as tumor burden, liver function and general

Early stage

This category includes asymptomatic patients with preserved liver function and either a solitary nodule ≤5 cm or up to three nodules <3 cm each. They are suitable for potentially curative treatments: surgical resection, liver transplantation and percutaneous ablation. A special group within early stage is that named very early stage or carcinoma in situ. Diagnosis of this type of tumor is currently feasible only by explant pathology. Tumors are <2 cm, have not formed an arterial vascularization

Summary

Hepatocellular carcinoma (HCC) has been recognized as a major health problem and emerged as one of the major causes of tumor death. Active research conducted during the last decades has prompted a better understanding of the disease and allowed a structured approach for its diagnosis and treatment. Several effective therapies are available for patients diagnosed with HCC, but still a majority of individuals are diagnosed at a too advanced stage where no active treatment is feasible. Hence, in

Acknowledgement

This work was in part supported by a grant of the Instituto de Salud Carlos III (grant 03/02).

Alejandro Forner received his M.D. degree in 1999 from “Miguel Hernández” University, Medical College, Alicante, Spain. He then completed his digestive diseases residency in 2005 at the Liver Unit of the Hospital Clinic, University of Barcelona, Spain. He currently works as an M.D. fellow of Barcelona Clinic Liver Cancer (BCLC), where he attends patients affected of HCC and carries on his doctorial thesis about early diagnosis of HCC.

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Amelia J. Hessheimer received her bachelor of science in chemistry in 2003 from Texas A&M University, College Station, TX, USA. She has completed 2 years of a medical degree at Vanderbilt Medical School, Nashville, TN, USA, and is currently on a 2-year leave of absence to perform research on hepatocellular carcinoma and liver transplant at the University of Barcelona, Spain. She has published several papers in the fields of inorganic chemistry and hepatic disease.

M. Isabel Real received her M.D. degree in 1977 from University of Barcelona Medical College, Spain. She completed her radiology residency in 1980. She has specialized in interventional radiology, particularly in abdominal field. She currently works in the Interventional Radiology Section, Radiology Unit, Hospital Clinic, Barcelona, Spain. She has published several reports about radiologist diagnosis of HCC and the benefits of transarterial chemoembolization.

Jordi Bruix obtained his M.D. degree in 1978 from University of Barcelona Medical College, Spain, and completed his specialty board in internal medicine and gastroenterology in 1982. He is senior consultant of hepatology in the Liver Unit and director of Barcelona Clinic Liver Cancer (BCLC), and associate professor of medicine at the University of Barcelona. He is member of several editorial boards and scientific societies and currently is associate editor of “Hepatology”. His scientific activity has been mainly related to the early diagnosis, prognosis and treatment of HCC, with more than 100 contributions as original studies, editorials and book chapters.

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