Radio frequency ablation for primary liver cancer: an evidence-based analysis.
OBJECTIVE
The Medical Advisory Secretariat undertook a review of the evidence on the safety, clinical effectiveness, and cost-effectiveness of radio frequency ablation (RFA) compared with other treatments for unresectable hepatocellular carcinoma (HCC) in Ontario.


BACKGROUND
Liver cancer is the fifth most common type of cancer globally, although it is most prevalent in Asia and Africa. The incidence of liver cancer has been increasing in the Western world, primarily because of an increased prevalence of hepatitis B and C. Data from Cancer Care Ontario from 1998 to 2002 suggest that the age-adjusted incidence of liver cancer in men rose slightly from 4.5 cases to 5.4 cases per 100,000 men. For women, the rates declined slightly, from 1.8 cases to 1.4 cases per 100,000 women during the same period. Most people who present with symptoms of liver cancer have a progressive form of the disease. The rates of survival in untreated patients in the early stage of the disease range from 50% to 82% at 1 year and 26% to 32% at 2 years. Patients with more advanced stages have survival rates ranging from 0% to 36% at 3 years. Surgical resection and transplantation are the procedures that have the best prognoses; however, only 15% to 20% of patients presenting with liver cancer are eligible for surgery. Resection is associated with a 50% survival rate at 5 years.


METHODS
RADIO FREQUENCY ABLATION RFA is a relatively new technique for the treatment of small liver cancers that cannot be treated with surgery. This technique applies alternating high-frequency electrical currents to the cancerous tissue. The intense heat leads to thermal coagulation that can kill the tumour. RFA is done under general or local anesthesia and can be done percutaneously (through the skin with a small needle), laparoscopically (microinvasively, using a small video camera), or intraoperatively. Percutaneous RFA is usually a day procedure.


METHODS
The leading international organizations for health technology assessments, including the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) and the International Network of Agencies for Health Technology Assessment (INAHTA), were scanned for previous systematic reviews on RFA. The Cochrane Library Database was also scanned. The most recent systematic review examined the literature up to October 2003. Five previous health technology assessments were found. To update the international systematic reviews, the Medical Advisory Secretariat systematically reviewed the literature from January 1, 2003 to the third week of April 2004. Peer-reviewed literature from EMBASE, MEDLINE (including in-process and other nonindexed citations) and the Cochrane Library Database were searched for the following search terms: Catheter ablationRadiofrequency or radio-frequency or radio frequency or RFA or RFTALiver neoplasms or liver cancer or hepatocellular or hepatocellular or hepaticCancerThe inclusion criteria were as follows:


METHODS
patients with primary hepatocellular carcinoma


METHODS
RFA used as the only treatment (not as an adjunct)LANGUAGE: publication in EnglishPublished health technology assessments, guidelines, and peer-reviewed literature (abstracts and in-progress manuscripts)


RESULTS
therapeutic response (% complete ablation), mortality, survival, and tumour recurrenceGrey literature, where relevant, was also reviewed.


RESULTS
The Medical Advisory Secretariat included 5 previous health technology assessments from 2002 to 2004 and 9 peer-reviewed studies from January 2003 to April 2004 in its review. The health technology assessments suggested that RFA is as safe and effective for treating up to 3 or 4 small (< 4 to 5 cm), unresectable liver tumours in the short term (2 years). One small randomized controlled trial (RCT) that compared RFA with percutaneous ethanol injection (PEI), another ablative technique, suggested that RFA is at least as safe and effective for small unresectable primary liver tumours compared to PEI. However, the patient populations and comparison technologies in the peer-reviewed literature and the previous health technology assessments were heterogeneous; therefore, meta-analyses could not be performed. RFA has also been used to treat colorectal and neuroendocrine liver metastases and kidney, lung, breast, and bone cancer. Although this report did not focus on these indications because of a paucity of published evidence of effectiveness, some individual patients with the above indications may benefit from RFA; therefore, RFA may quickly diffuse into these areas. Various clinical trials focussing on these indications are underway.


CONCLUSIONS
Level 2 evidence suggests RFA is as safe and perhaps more effective than percutaneous ethanol injection to treat HCC.RFA and percutaneous ethanol injection are more effective and more cost-effective than transcatheter arterial chemoembolization.RFA is marginally more expensive, yet more cost-effective than percutaneous ethanol injection.Complications are few, but experienced interventional radiologists should do RFA.RFA may benefit some patients with liver metastases or other primary cancers, although published evidence of effectiveness has not yet been established.