Hepatectomy versus radiofrequency ablation for early hepatocellular carcinoma
Authors: Tetsuji Fujita
Journal: Journal of Hepatology (2009)

Dr. Hasegawa and the Japanese Liver Cancer Study Group compared the outcome of surgical resection with those of percutaneous ablation therapies using the prospectively collected data on patients with a single hepatocellular carcinoma (HCC) nodule or no more than three nodules each measuring less than 3 cm in diameter who underwent either partial hepatectomy (n = 2857), radiofrequency ablation (RFA) (n = 3022), or percutaneous ethanol injection (n = 1306) between 2000 and 2003. [[1]Hasegawa K. Makuuchi M. Takayama T. Kokudo N. Arii S. Okazaki M. et al.Surgical resection vs. percutaneous ablation for hepatocellular carcinoma: a preliminary report of the Japanese nationwide survey.J Hepatol. 2008; 49: 589-594Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar]. In their clinically valuable study, it is estimated that more than 95% of patients in each group will be alive at 2 years after initial therapy, while the estimated 2-year time-to-recurrence rate in patients who underwent partial hepatectomy (35.5%) is significantly lower than that in patients with RFA (55.4%) or with percutaneous ethanol injection (73.3%). In a Cox proportional hazard model in which 9 patient-related or tumor-related factors and types of therapy were entered, surgical resection is an independent negative predictor for recurrence. The authors conclude that surgical resection may offer some advantages over percutaneous ablation therapies for patients with primary HCC if the number of HCC nodules is 3 or less and the maximum diameter of each nodule is less than 3 cm. Although several years have passed since the last entry to the study, the median follow-up period was 10.4 months and a quarter of patients enrolled in the study were followed up only over a period of 4.8 months. First, I would like to ask the authors how many and why patients were lost to follow-up, and whether the rates of censored patients were similar among the three groups. Child–Pugh score, serum albumin levels, and indocyanine green retention at 15 min were significantly better in the resection group than in ablation therapy groups. The number of tumors, also, was smaller in the former group than in the latter groups. These findings suggest that the treatment of choice was dependent on functional hepatic reserve and tumor status. These factors that were entered into a Cox proportional hazard model are likely to be correlated to each other and associated with a specific type of treatment modalities. Second, I would like to ask the authors whether step-wise multiple logistic regression analysis is more appropriate than a Cox proportional hazard model to elucidate the factors independently contributing to tumor recurrence in such situations. When compared with previous reports showing that local recurrence rates after RFA of HCC vary from 2% to 36% [[2]Lam V.W. Ng K.K. Chok K.S. Cheung T.T. Yuem J. Tung H. et al.Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma.J Am Coll Surg. 2008; 207: 20-29Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar], the recurrence rate of 55.4% at 2 years after RFA seems exceptionally high. I am concerned that true local recurrence, newly developed HCC nodules in the liver remnant, and extrahepatic recurrence are all included in the analysis of tumor recurrence. Third, I would like to ask the authors how local or distant recurrence was defined and whether surgical resection as an initial therapy was associated with the reduction in local recurrence rates. According to a recent work comparing the outcomes of repeat hepatectomy with those of salvage RFA in patients with recurrent HCC after partial hepatectomy, among intrahepatic recurrences approximately 90% of recurrent tumors developed at a new area within the liver [[3]Liang H.H. Chen M.S. Peng Z.W. Zhang Y.J. Zhang Y.Q. Li J.Q. et al.Percutaneous radiofrequency ablation versus repeat hepatectomy for recurrent hepatocellular carcinoma: a retrospective study.Ann Surg Oncol. 2008; 15: 3484-3493Crossref PubMed Scopus (106) Google Scholar]. HCC accompanying cirrhosis is an organ disease, and the first nodule treated is usually only a prelude to others [[4]Nakashima O. Kojiro M. Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology.J Hepatobiliary Pancreat Surg. 2001; 8: 404-409Crossref PubMed Scopus (70) Google Scholar]. Therefore, incidence of appearance of new lesions in cirrhotic liver appears not to be an adequate measure to evaluate the efficacy of each therapeutic modality for HCC. Apart from orthotropic liver transplantation that should be reserved for selective patients with end-stage liver disease, when allowed by the hepatic functional reserve and tumor status, partial hepatectomy has been considered as the first-line treatment for both primary and recurrent HCC. However, with the advances in operator skills and equipment used for RFA such as expandable or open-perfused electrodes and computer-assisted generator, it appears that RFA has become an equally effective alternative to surgical resection for early HCC. In a recent Italian cohort study, complete local responses to RFA were sustained during the median follow-up period of 31 months in 212 of 218 patients with a single HCC nodule 2.0 cm or less in diameter who received 1 or 2 sessions of RFA [[5]Livraghi T. Meloni F. Rolle M. Di Stasi M. Solbiati L. Tinelli C. et al.Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still be treatment of choice?.Hepatology. 2008; 47: 82-89Crossref PubMed Scopus (902) Google Scholar]. Hepatic resection, especially anatomical resection, is seemingly the more suitable option for obtaining the complete tumor ablation including a layer of tissue surrounding it, whereas RFA is likely to have advantages of being less invasive, incurring less costs, and requiring shorter duration of hospital stay. Finally, I would like to ask the authors whether subgroup analysis according to the size and number of tumors would be helpful to clarify the role of surgical resection and RFA in the treatment of HCC in their large patients.