While thousands of randomized controlled trials (RCT) inform the treatment of many of the most
lethal cancers, in hepatocellular carcinoma (HCC), only 77 RCT studies were published between 1978 and 2005.
This systematic review sought to identify RCTs pertaining to the treatment of liver cancer published from January
2006 to July 2009 and evaluate their methodological quality. Thirty RCTs published in English were identified.
Most (18) originated in Asia, one third in Europe and two were multi-country studies. A total of 4,139 patients
were enrolled in these RCTs, for a mean of 138 patients per trial. 73% of these trials were of high methodological
quality. The RCTs found that using monoclonal antibodies or gene therapy in conjunction with liver
transplantation may extend transplant indications and that the use of interferon, lipiodol or adoptive
immunotherapy in conjunction with liver resection may improve survival, but that this would need validation by
larger studies. Radiofrequency ablation (RFA) is equally effective, and has fewer complications than liver
resection. RFA is superior to percutaneous ethanol injection (PEI) for local disease control and combining RFA
and PEI improves overall survival. The role of arterial occlusion during RFA awaits further validation.
Transarterial chemoembolization (TACE) combined with RFA and immuno-modulators may warrant future
exploration. Two large, high quality sorafenib trials confirmed the role of this agent in the systemic treatment of
HCC. The octreotide trials have overall been disappointing, but benefits may exist for HCCs expressing
somatostatin receptors. Although the last 4 years have witnessed significant progress in this field, the average of 9
RCTs per year for HCC treatment remains well behind the level of research activity in other cancers.
Keywords: Hepatocellular carcinoma, randomized clinical trials, liver resection, liver transplantation,
immunotherapy, local ablative therapy, percutaneous injection, radiofrequency ablation, cryotherapy, transarterial
chemotherapy, transarterial embolization, transarterial chemoembolization, systemic chemotherapy.
