Percutaneous ablative treatments of hepatocellular carcinoma
Authors: Gian Ludovico Rapaccini
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. See Article on Page 1579 The history of percutaneous ablation of primary and secondary liver tumors dates back to the mid‐1980s, when, within the space of a few months, researchers in Japan and Italy published the first reports of ultrasound‐guided injections of ethanol to ablate hepatocellular carcinomas (HCCs) and liver metastases.1 Later, other types of technology were developed to produce necrosis of tumor tissue using radiofrequency, laser, or microwave energy—all delivered via a needle inserted into the focal liver lesion under imaging guidance or during laparoscopy.3 These methods have been used mainly to treat HCCs in patients with cirrhosis who were ineligible for surgical resection, and each has been thoroughly analyzed in the literature in terms of the outcome of treatment (overall survival, disease‐free survival, tumor progression), contraindications, risks, and complications. As far as percutaneous ethanol injections (PEI) are concerned, the 5‐year survival rates in patients with HCCs measuring less than 3 cm range from 47% to 65%; and in a recent study of 685 Japanese patients, the 5‐, 10‐, and 20‐year survival rates—49%, 18%, and 7.2%, respectively—were similar to those observed in patients with cirrhosis who did not have HCC.6 For larger HCCs, however, PEI has been shown to produce incomplete necrosis of the tumor tissue owing to the heterogeneous consistency of these tumors, which hinders uniform intralesional distribution of the alcohol. This limitation can be overcome with radiofrequency ablation (RFA), which is based on the conversion of radiofrequency energy to heat. In the treatment of HCCs exceeding 2 cm in diameter, RFA is associated with higher rates of complete necrosis and better long‐term outcomes than PEI.7 In contrast, PEI has displayed good efficacy in the treatment of tumors measuring less than 2 cm, particularly those located in "problem" areas of the liver or adjacent to blood vessels, settings in which the diffusion of heat is less advisable.8 Microwave ablation (MWA) creates an electromagnetic field within the tumor, which induces uniform rotation of the tissue molecules and heat production that results in necrosis.9 In some studies, MWA has been compared with RFA for the treatment of HCCs of different sizes (<3 cm and <5 cm), but no significant differences have been observed in either setting in terms of the completeness of tumor necrosis, disease recurrence, survival, or complication rates.10 Laser thermal ablation has also been associated with high rates of complete necrosis, an average of 95%, in HCCs measuring less than 3 cm;12 but compared with other methods, it is based on relatively sophisticated technology and requires much more substantial operator experience since it involves placement of multiple optical fibers within the neoplastic lesion according to a programmed spatial distribution scheme. Given their widespread use, the excellent results they produce in terms of survival (comparable to those reported after surgical resection in some studies13) and their acceptable complication rates,15 tumor ablation techniques are now listed in the American Association for the Study of Liver Diseases guidelines among the potentially "curative" treatments for HCC.17 Unfortunately, however, randomized, prospective comparisons of the various techniques (e.g., RFA versus MWA) are still quite rare, and thus far no one technique has emerged as significantly more effective than the others. In this issue of hepatology Wang et al. report the results of a randomized, controlled multicenter trial comparing percutaneous cryoablation (CRYO) and RFA in patients with cirrhosis, Child‐Pugh class A or B liver function, and one or two HCC nodules measuring 4 cm or less.18 The CRYO method is relatively new and causes intralesional ice formation, cellular dehydration and lysis, and obliteration of the newly formed blood vessels within the tumor.19 This was a well‐designed study, and the clinical characteristics of the patients in the two treatment groups were similar. The primary end points were local tumor progression at 3 years and safety. As for the former, CRYO proved to be significantly superior to RFA in patients with larger tumors (i.e., 3.1‐4 cm in diameter). The two methods were not significantly different in terms of complication rates, which were less than 4% in both groups, or survival (overall and tumor‐free) at 1, 3, and 5 years. The main contribution of this study is the demonstration that percutaneous ablation can be effective for HCCs up to 4 cm in diameter. The superiority of CRYO over RFA in the larger tumors (3.1‐4.0 cm) in terms of local tumor progression can theoretically be attributed to its ability to necrotize larger volumes of tissue, which increases the chances of ablating microsatellite lesions that are always possible with lesions of this size. The study did not compare the costs of the two procedures, and as the authors themselves point out, this is an important factor in today's economy. The use of ablative therapies for HCC is still surrounded by a number of other unanswered questions. For example, although the efficacy of PEI for treatment of lesions less than or equal to 2 cm in diameter is now well documented, for larger tumors it is still too early to conclude that one technique is significantly better than the others (RFA, MWA, CRYO) in terms of complete necrosis rates or actuarial survival curves, although in this field it is always best to verify actual survival instead of relying on statistical projections alone. In addition, we still do not have reliable data on the efficacy of percutaneous ablation techniques combined with other types of treatment (e.g., intra‐arterial chemoembolization + RFA), an approach that might be useful for managing larger tumors. And finally, further work is needed to define the role(s) of percutaneous ablation in patients with HCC who may be eligible for liver transplantation (e.g., downstaging of the tumor to allow access to the waiting list, treatment of patients who are already on the list to avoid dropout).20