TACE versus TAE as Therapy for Hepatocellular Carcinoma

Maria Pleguezuelo; , Laura Marelli; Maria Misseri; Giacomo Germani; Vincenza Calvaruso; Elias Xiruochakis; Manousou Pinelopi; Andrew K Burroughs

Disclosures

Expert Rev Anticancer Ther. 2008;8(10):1623-1641. 

In This Article

Abstract and Introduction

Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.

Primary hepatocellular cancer (HCC), in 80% of cases, is a complication of cirrhosis and is the fifth most common cancer in the world and the third cause of cancer mortality,[1] representing 85-90% of malignant liver lesions. Approximately 560,000 new cases of HCC are diagnosed every year causing 550,000 deaths. HCC is the cancer with the highest increase in incidence within the last 10 years in USA[2] and is the leading cause of death in cirrhotic patients in Europe.[3]

In patients with early-stage tumors, curative therapies can be applied, including resection, liver transplantation (LT) and percutaneous ablation, such as percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA).[3] However, although these treatments potentially lead to 5-year survival rates of 50%, they are applicable in only 30-40% of patients with HCC. Thus, most patients are only suitable for locoregional therapies or palliative care.

Transarterial embolization (TAE) was first used to treat HCC by Doyon et al. in 1974 in Japan.[4] Initially, gelatin sponge particles and anticancer agents were used; in the 1990s lipiodol was introduced. Today, transarterial chemoembolization (TACE) has become the most common approach for the management of HCC without curative options.

Despite the wide use of embolization therapy for HCC for many years, its efficacy was controversial until two randomized controlled trials (RCTs)[5,6]and three meta-analyses of randomized trials[7,8,9] showed improvement in survival compared with best supportive care. Asymptomatic patients with multinodular noninvasive tumors appear to be the best candidates for embolization. In these cases, the end point of therapy is to prolong survival.

During its progression, HCC exhibits intense neoangiogenic activity and is mostly dependent on the hepatic artery for blood supply, while the rest of the liver is supplied by the portal vein.[10] This provides the rationale to use arterial obstruction as an effective therapeutic option, as it induces ischemic tumor necrosis.

The term TAE refers to the embolization of the hepatic artery that may or may not be preceded by the administration of lipiodol, without using any chemotherapeutic agents. When TAE is combined with prior injection into the hepatic artery of chemotherapeutic agents, mixed with lipiodol, the procedure is known as TACE.

However, it is not clear whether embolization alone gives the same survival advantage as chemoembolization[5,11,12] nor whether specific patient characteristics or any particular technique in performing transarterial therapy is better than any other. Furthermore, it has been suggested that TAE performed with a permanent embolic agent alone, such as microspheres, through superselective catherization of the feeding artery of the tumor, may enhance the ischemia avoiding the use of potentially toxic chemotherapeutic agents. However, the impact on survival compared with conventional TACE remains unclear.

Although the therapeutic benefit of TACE has been only demon­strated in patients with HCC without curative options, it is currently being used as a bridge therapy for patients awaiting LT, based on the assumption that this procedure may prevent drop-outs due to tumor progression.[13]

The studies included in our review were identified by searching Medline using the following key words: 'hepatocellular carcinoma' or 'HCC' or 'hepatic tumor' or 'liver tumor' or 'hepatic cancer' or 'liver cancer' AND 'TACE' or 'TAE' or 'chemoembolization' or 'embolization' AND 'clinical trials' in English and non-English languages. We also manually searched general reviews on HCC and references from published clinical trials. Some retrospective studies have been included in order to point the lack of prospective studies regarding some of the topics covered.

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