Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies?

Hepatocellular carcinoma (HCC) generally occurs in patients with cirrhosis. Curative options, such as liver transplantation, hepatic resection, and percutaneous alcohol injection, are applicable to a minority of cases. Because systemic chemotherapy and radiation therapy provide dismal results, transarterial chemoembolization (TACE) remains the sole approach to antagonizing the cancer growth in most patients. Although most tumors show an extensive necrosis after TACE, the beneficial effect on survival has not been properly substantiated, so that its application still remains a matter of debate. This review analyzes the results of randomized clinical trials on TACE. In most studies, TACE did not increase the survival of patients as compared with the palliative treatment. However, several methodologic and technical pitfalls may have adversely affected the results of these trials, such as inadequate patient selection and statistical power of the study design, a nonoptimal procedure, and treatment repetition not tailored to the cancer response and patient tolerance. Nonetheless, the literature will hardly be enriched by new trials including untreated patients because, wrong or right, TACE is currently considered the standard treatment of unresectable HCC. It seems more realistic to expect randomized studies comparing different techniques and time schedules of treatment, as well as TACE alone versus combined procedures.