Authors' objectives: Hepatocellular carcinoma (HCC) is increasingly detected following widespread sonographic screening of high risk patients, especially those with liver cirrhosis and chronic viral hepatitis. Although it occurs less frequently in Northern and Western Europe and in North America than in other parts of the world, in the last 15 years the incidence of HCC has been increasing steadily in the United States. It has been suggested that this incidence will continue to grow in the United States since a significant portion of the immigrant population comes from areas of the world where HCC is endemic. In Canada, the incidence of HCC and associated mortality rates are likely to increase because of the high prevalence of hepatitis C and the large increase in the number of hepatitis B carriers caused by immigration from areas where the virus is common. The treatment of choice for a small percentage of patients with localized disease is hepatic resection (HR). A large number of patients with HCC are not operable because of various factors. According to the United States National Cancer Institute's PDQ database there is no standard therapy for localized unresectable HCC. Among the newer techniques which are currently under clinical evaluation, percutaneous ethanol injection therapy (PEIT) has been identified as a method to treat patients with HCC and cirrhosis in whom resection is unsafe. Treatment of hepatic metastasis (HM) varies with the underlying disease, extent of metastatic disease in the liver and in other sites, and availability of effective systemic therapy. According to PDQ the standard treatment for colorectal HM is hepatic resection. However, relatively few patients are candidates for surgery. For other patients many systemic and regional therapies have been tried including PEIT. PEIT has emerged as a treatment for hepatic cancers, especially in patients with poor hepatic function, who are not candidates for surgery. It has been performed, mostly in Asia and in some European countries, as a treatment for hepatic cancers with both curative and palliative intent. To date, reported experience with PEIT has focused mainly on the treatment of HCC and little information is available regarding its use as a treatment for HM.

Authors' results and conclusions: There appear to be no reports of adequate prospective controlled studies on the efficacy of PEIT for hepatic tumors as compared to other treatments or no treatment. Most published reports have been based on retrospective analyses of the experiences with PEIT at different centers, with no controls or with historical controls. Only one published prospective randomized controlled trial was located. In that study, PEIT in a small number of patients (n=15) with HCC lesions larger than 5 cm in diameter was compared with no treatment. The reported results are not directly comparable as there is considerable variation between published studies. Results in the reviewed studies suggest that carefully selected patients (those with few small and well differentiated hepatic tumors and good functional liver reserve) may benefit from PEIT. Authors of most of these studies propose PEIT as a treatment of choice for patients with small and few HCCs recruited by US screening, who are not candidates for orthotopic liver transplantation or hepatic resection. The short-term efficacy of PEIT for HCC in terms of percentage of tumor necrosis has been reported to be high. The published rates of complete necrosis range between 36% and 90%. Complete necrosis cannot always be obtained with PEIT alone due to technical limitations such as the site of the tumor, or inadequate sonographic visualization for injection. Most of the reviewed studies suggest that the local efficacy of PEIT is dependent on tumor size. Tumor recurrences are noted frequently at long-term follow-up after initial success with PEIT. Many investigators have reported similar recurrence rates after PEIT as compared with those after HR in historical controls. Most recurrences after PEIT occur in other parts of the liver as new lesions. Since most of the recurrences are due to new lesions rather than progression of treated lesions, it has been suggested that the success of PEIT or of any other local therapy is limited by this process. The long-term efficacy of PEIT in terms of survival rates has been reported to be comparable to that obtained after HR in comparable patients. The reviewed literature suggests that survival rates are higher in patients with better liver function, who have 1 or up to 3 lesions, smaller than 3 cm in diameter. Shiina et alreported 5-, 7-, and 10-year survival rates of 55%, 51%, and 32% in 140 patients with multiple HCCs (2 cm or smaller). For 83/140 patients (with single HCC of 2 cm or smaller) the 5-, 7-, and 10-year survival rates were 72%, 66%, and 66%, respectively. The natural course of metastatic disease strictly limits the applicability of PEIT. It differs from that of HCC and the alcohol diffuses less readily in HM than in HCCs. The few published studies on the use of PEIT in the treatment of HM suggest that PEIT for HM is palliative. However, no prospective controlled trials have been reported, and long-term survival data are not available. Single, unresectable HMs of colorectal adenocarcinoma and endocrine metastases seem to be the most suitable indications for PEIT. However, at the First International Workshop on Liver Tumor Ablation (November, 1992), the unanimous conclusion reached was that PEIT is relatively ineffective for the treatment of colorectal hepatic metastases.

Authors' recommendations: PEIT has not been evaluated in well-designed prospective controlled trials. The quality of the available evidence is limited in some respects and does not allow an adequate evaluation of its therapeutic effect. The low treatment-related morbidity and mortality, the ability to spare functioning liver tissue, the easy feasibility of repeated treatment for recurrences and the low cost of the treatment makes PEIT an attractive method to treat small hepatic tumors in patients who do not respond to or who are not candidates for conventional therapy. The limited available evidence suggests that carefully selected patients with HCC may benefit from PEIT. In the reviewed literature, most investigators proposed it as a treatment of choice for patients with small and few lesions recruited by US screening, who are not candidates for surgery. However, there is still little comparative information on long-term outcomes. There is limited experience with the use of PEIT as a treatment for HM and its role for this indication is yet to be determined. According to the reviewed evidence, PEIT does not appear to be an effective treatment for HM. Long-term, well designed prospective controlled clinical trials of sufficient power are needed to establish the benefit of PEIT as a treatment for hepatic cancer.

Authors' methods: Systematic review

Project Status: Completed

Year Published: 1997

URL for published report: https://www.ihe.ca/advanced-search?type=1020

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Institute of Health Economics

Contact Address: 1200, 10405 Jasper Avenue, Edmonton, Alberta, Canada, T5J 3N4. Tel: +1 780 448 4881; Fax: +1 780 448 0018;

Contact Name: djuzwishin@ihe.ca

Contact Email: djuzwishin@ihe.ca

Copyright: Alberta Heritage Foundation for Medical Research, 1997