An overview of evidence-based management of hepatocellular carcinoma: a meta-analysis

Abstract

Introduction: An increasing trend of incidence in hepatocellular carcinoma (HCC) has been recorded in most developed countries. HCC ranks among the ten most common cancers worldwide. The health costs and burden to the economy implicated by HCC are huge. In recent years, the surveillance programs and screening for the disease, in addition to increasing awareness, led to the detection of smaller precursor lesions of HCC in the liver. The rise of molecular-targeted therapies and the publication of various conflicting guidelines on the management of the disease demand a review of evidence into the curative therapies and medical management of HCC.

Aims: The primary objective was to identify the survival benefit of the primary medical modalities in HCC, as more trials were uncovered between 2005 and 2010. The secondary objective was to conduct a meta-analysis. Selection criteria were implemented to select randomized controlled trials (RCTs), to include in this study. After selection, all the articles were ranked according to their strength.

Materials and methods: The MEDLINE, CANCERLIT, Embase databases, and the Cochrane Library were reviewed using the national library of health website. The time limit used for searching for RCTs was between January 2005 and December 2010. Overall survival and the cumulative probability of no recurrence were the primary endpoints considered in the studies to be assessed. These endpoints were measured over one, two, or three years, depending on the size of the study and the length of follow-up. The software package comprehensive meta-analysis ver 2.0.exe (Biostat, USA) was used to comply with the results, to conduct the meta-analysis, and help with analyzing the data.

Results: The original general search yielded 193 RCTs between 2005 and 2010. Only 32 studies met the inclusion criteria. However, after the ranking of the studies according to strength, only 17 studies were eventually selected. The 17 studies were subsequently classified according to the following; surgical resection (n = 2); percutaneous treatments (n = 5); chemoembolization (n = 1); systemic treatments (n = 8); and other treatments (n = 1). Randomized studies comparing the percutaneous ethanol injection (PEI) to the surgical resection were inconclusive. However, percutaneous treatments showed results similar to surgical resection in terms of overall survival. The meta-analysis comparing PEI to radiofrequency ablation (RFA) showed RFA to be superior to PEI in terms of overall survival at three years (odds ratio 1.698; 95% CI 1.206 - 2.391; P = 0.002). When adverse events were considered there was no statistically significant difference between the RFA and PEI groups (odds ratio 1.199; 95% CI 0.571- 2.521; P = 0.632).

Conclusion: RFA should be the first-line treatment in patients with a single small HCC tumor ≤ 3 cm. Careful patient selection is crucial prior to transarterial chemoembolization (TACE), as the procedure may be associated with an increased risk of liver failure. Tamoxifen has no role to play in the treatment of HCC. Sorafenib should be the first-line treatment in patients with advanced and inoperable HCC. The role of Sorafenib in the management of early stage HCC remains to be determined.