|Year : 2017 | Volume
| Issue : 4 | Page : 625-630
Efficacy comparison of radiofrequency ablation and hepatic resection for hepatocellular carcinoma: A meta-analysis
E Changyong1, Dan Wang2, Yang Yu3, Hongyu Liu1, Hui Ren4, Tao Jiang5
1 Department of Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
2 Department of Breast Surgery, The Second Hospital of Jilin University, Changchun 130041, China
3 Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
4 Department of Colorectal Surgery, The Second Hospital of Jilin University, Changchun 130041, China
5 Department of Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033; Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
|Date of Web Publication||13-Sep-2017|
Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033; Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033
Source of Support: None, Conflict of Interest: None
Objectives: The objective of this study is to compare the therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for the treatment of hepatocellular carcinoma (HCC).
Materials and Methods: A literature search was performed for comparative studies reporting outcomes of both RFA and HR for HCC. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.
Results: A total of 4812 patients with HCC were included, with 2419 in the RFA group and 2393 in the HR group. The 3- and 5-year overall survival rates in the HR group were significantly higher than those in the RFA group (OR: 0.68, 95% CI: 0.58–0.79, P < 0.00001; OR: 0.57, 95% CI: 0.50–0.65, P < 0.00001, respectively). 1-, 3-, 5-year disease-free survival and correspond recurrence-free survival rates were all better in HR group.
Conclusion: RFA gets promising clinical outcomes for HCC treatments but is not yet comparable to surgery. HR is still the first-line treatment for HCC.
Keywords: Efficacy, hepatic resection, meta-analysis, radiofrequency ablation
|How to cite this article:|
Changyong E, Wang D, Yu Y, Liu H, Ren H, Jiang T. Efficacy comparison of radiofrequency ablation and hepatic resection for hepatocellular carcinoma: A meta-analysis. J Can Res Ther 2017;13:625-30
|How to cite this URL:|
Changyong E, Wang D, Yu Y, Liu H, Ren H, Jiang T. Efficacy comparison of radiofrequency ablation and hepatic resection for hepatocellular carcinoma: A meta-analysis. J Can Res Ther [serial online] 2017 [cited 2019 Jan 17];13:625-30. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/625/214470
| > Introduction|| |
Hepatocellular carcinoma (HCC) is among the most common malignant tumors and leading causes of deaths worldwide. Tens of thousands of people die of this disease every year. Risk factors include hepatitis B, hepatitis C, comorbidities, and environmental factors. Advances have been made in treatment, imaging, interventional radiology, surgical techniques, and liver transplantation. Besides chemo-and radio-therapies, treatments toward HCC conclude surgical resection, radiofrequency ablation (RFA), microwave ablation, transarterial chemoembolization, and transarterial radioembolization.,, Hepatic resection (HR) is commonly used as first-line therapy for patients with HCC. Liver function should be carefully evaluated before surgery, as larger sizes and increased numbers of tumors are high-risk factors for recurrence after surgical resection. Advanced tumors, tumor location near major intrahepatic vessels, multifocal tumors, or poor hepatic functional reserve may exclude the patients from candidates for surgery resection. Therefore, evaluation of clinical effects of alternative techniques has been drawing attention.
RFA is one kind of minimal invasive surgery technique frequently used in the treatment of solid tumors and cardiac diseases. Under guidance of imaging methods such as laparoscope and ultrasound, the electrode is directly placed at the tumor lesion. Through delivering radiofrequency energy, the tumor and adjacent tissues are eliminated. After years of application, RFA is a recommended therapeutic option for HCCs not fit for surgery. However, it is still highly controversial whether it is comparable with surgery as the first-line treatment. Results are inconsistent from published researches that compare the clinical outcomes of RFA and HR in treatment of HCC.
Here, we did quantitatively work to summarize different articles that comparing the clinical efficacy of RFA and surgery resection. Using evidence-based medicine method, we aim to verify if RFA is comparable to HR and provide reference to clinicians.
| > Materials and Methods|| |
We searched PubMed, EMBASE, and Cochrane database for articles up to May 1, 2017, using a MeSH heading search strategy with the terms: “hepatic resection” or “liver resection” or “liver surgery,” “radiofrequency ablation” “hepatocellular carcinoma,” or “liver cancer.” The search was restricted to studies on humans and in English.
All retrieved articles in reference lists were manually searched for additional studies. Data were extracted independently by two reviewers and discussions were made to solve discrepancies. Parameters were extracted from each study: (1)First author and year of the publication, (2) study design and patients' characteristics, and (3) clinical outcomes. The end-points were efficacy indicators including overall and disease-free survival (DFS) rates at 1, 3, and 5 years.
Criteria for inclusion and exclusion
To be included in the meta-analysis, a study had to be qualified as: (1) Comparing the therapeutic effects of RFA and HR for the treatment of HCC. In the present study, small HCC was defined as tumor(s) ≤3 cm in size; (2) reporting clear data of the outcome measures mentioned above; and (3) if two or more studies were reported by the same authors in the same institution, either the study of higher quality or the most recent publication was included in the analysis.
Conference abstracts, editorials and expert opinions, letters, systematic reviews or case reports were excluded; studies without clearly reported outcomes of interest were excluded; studies that mixed other effective interventions (i.e., TACE) in either treatment group or control group were also excluded from the analysis.
The meta-analysis was performed using the Review Manager software (RevMan, version 5.3, Cochrane Collaboration, Oxford, UK). The dichotomous data of the RFA and HR groups are reported as the case number (n). We analyzed dichotomous variables using the estimation of odds ratios with a 95% confidence interval. Heterogeneity was evaluated by Chi-square and I 2. We considered heterogeneity to be present if the I 2 statistic was >50%. P < 0.05 was considered statistically significant.
| > Results|| |
Selection of trials
The initial search identified 1578 potentially relevant articles, which were evaluated by title and abstract. Of these, 36 articles were qualified for selection [Figure 1]. After further assessment, a total of 25 articles met the requirements and were included in the meta-analysis, with three randomized controlled trails (RCTs) among them.,,
The characteristics of the included studies are provided in [Table 1]. A total of 4812 patients with HCC were included in these studies, with 2419 in the RFA group and 2393 in the HR group. One study was conducted in the United States  and Australia, three in Japan,,, Italy ,, and South Korea,,, and eleven in China, respectively. The sample size of each study varied from 52 to 605 patients. The size of tumor ranged from ≤2 to ≤7 cm.,,,,,,,,,,,,,,,,,,,,,,,,
We have calculated 1-, 3- and 5-year overall survival (OS) rates based on data demonstrated by the included studies. For 1-year OS rates, there is no significant difference between RFA and HR group. However, as time extends, the 3- and 5-year OS rates are statistically higher in HR group [Figure 2] and [Figure 3].
|Figure 2: Overall survival rate analysis, comparing patients in the radiofrequency ablation group to those in the hepatic resection group|
Click here to view
|Figure 3: Funnel plot of comparison of radiofrequency ablation and hepatic resection group|
Click here to view
As RFA is commonly recommended for HCC patients with smaller tumors or at earlier stages, the corresponding OS rates were also analyzed based on data illuminated in studies that focus on small/early stage HCC. Here, small or early stage HCC is identified as size of single nodule ≤3 cm. The 1-year OS rate is promising, as better outcome is observed in RFA group. However, when it comes to 3- and 5-year OS rates, especially 5-year OS rate, HR group achieved superior efficacy [Figure 4] and [Figure 5].
|Figure 4: Overall survival rate analysis, comparing patients in the radiofrequency ablation group to those in the hepatic resection group with small/early stage hepatocellular carcinoma|
Click here to view
|Figure 5: Funnel plot of comparison of overall survival rates in the radiofrequency ablation group to those in the hepatic resection group with small/early stage hepatocellular carcinoma|
Click here to view
Similar results are observed in DFS rates and recurrence-free survival (RFS)/tumor-free survival rates. HR group shows obvious advantages in 1-, 3- and 5-year DFS [Figure 6] and [Figure 7].
|Figure 6: Disease-free survival rate analysis, comparing disease-free survival rates in the radiofrequency ablation group to those in the hepatic resection group|
Click here to view
|Figure 7: Funnel plot of comparison of disease-free survival rates in the radiofrequency ablation group to those in the hepatic resection group|
Click here to view
The 1- and 3-year RFS rates tend to be better in HR group while without significant difference. However, the 5-year RFS is higher in patients received surgery resection [Figure 8] and [Figure 9].
|Figure 8: Recurrence-free survival rate analysis, comparing recurrence-free survival rates in the radiofrequency ablation group to those in the hepatic resection group|
Click here to view
|Figure 9: Funnel plot of comparison of recurrence-free survival rates in the radiofrequency ablation group to those in the hepatic resection group|
Click here to view
| > Discussion|| |
Currently, HR remains to be the first choice for the treatment of resectable tumors in liver. RFA is mainly used for primary hepatic carcinoma that cannot be resected, recurrent hepatic carcinoma after surgery, and metastatic hepatic carcinoma., The divergence still exists if RFA is a good replacement for HR for treatment of HCC. According to Hiraoka et al., there were no significant differences in OS and DFS rates between the HR and RFA groups. In their research, OS and DFS were a little higher in RFA group. However, many other researchers thought that surgery resection got better outcomes, especially long-term efficacies. For example, in Parisi's investigation, surgical resection improved the OS and RFS during 5 years of follow-up in comparison with RFA. Hence, the results from the previous studies have been inconsistent.
We used meta-analysis to compare the efficacy of RFA and HR in treating HCC. No difference is found between HR and RFA group regarding the 1-year OS rate in HCC tumor sized ≤7 cm. However, HR is associated with higher 3- and 5-year OS rates. As mentioned above, RFA is thought to be effective in small or very early/early stage HCC. For tumors sized ≤3 cm, RFA group shows more satisfying 1-year OS rate. However, the 3- and 5-year OS rates are still higher in HR group. In addition, the 1-, 3-, and 5-year DFS rates, and 5-year RFS rate are significantly higher in HR group.
The reason behind such results may be that RFA could probably miss tumor lesions when there are more than one nodules. By adopting laparoscopic and open approaches, tumor lesions are easier to find, which is the weak point of percutaneous RFA. The survived nodules might be the cause of tumor recurrence and poor survival rates.,
Improvements can be made for this meta-analysis. Among all the 25 eligible studies, only three are RCTs whereas the remaining studies are retrospective studies. Except for RCTs, in several studies, RFA and HR were used in patients that possessed different clinical characteristics, which could make the results biased. We warrant more RCTs to validate the results of the current study.
| > Conclusion|| |
Our meta-analysis concludes a total of 4812 hepatocellular carcinoma patients, with 2419 in the RFA group and 2393 in the HR group. After comparing of 1-, 3-, 5-year overall survival rates, disease-free survival and corresponding recurrence-free survival rates, results reveal that HR group got significantly higher 3- and 5-year overall survival rates, and 1-, 3-, 5-year disease-free survival and correspond recurrence-free survival rates. All these above proved that RFA is an effective approach to treat hepatocellular carcinoma but not yet good enough to replace HR, as better overall and disease-free survival rates are observed in patients underwent HR. HR still has its irreplaceable role in first-line treatment for HCC, while in the situations that the condition of patients is not suitable to perform operation, RFA might be the solution.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Yang JD, Roberts LR. Hepatocellular carcinoma: A global view. Nat Rev Gastroenterol Hepatol 2010;7:448-58.
Cillo U, Noaro G, Vitale A, Neri D, D'Amico F, Gringeri E, et al.
Laparoscopic microwave ablation in patients with hepatocellular carcinoma: A prospective cohort study. HPB (Oxford) 2014;16:979-86.
Xue T, Le F, Chen R, Xie X, Zhang L, Ge N, et al.
Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: A large cohort study. Med Oncol 2015;32:64.
Sacco R, Mismas V, Marceglia S, Romano A, Giacomelli L, Bertini M, et al.
Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives. World J Gastroenterol 2015;21:6518-25.
Song T. Recent advances in surgical treatment of hepatocellular carcinoma. Drug Discov Ther 2015;9:319-30.
Huang J, Yan L, Cheng Z, Wu H, Du L, Wang J, et al.
A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg 2010;252:903-12.
Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, et al.
A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006;243:321-8.
Feng K, Yan J, Li X, Xia F, Ma K, Wang S, et al.
A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol 2012;57:794-802.
Tohme S, Geller DA, Cardinal JS, Chen HW, Packiam V, Reddy S, et al.
Radiofrequency ablation compared to resection in early-stage hepatocellular carcinoma. HPB (Oxford) 2013;15:210-7.
Gory I, Fink M, Bell S, Gow P, Nicoll A, Knight V, et al.
Radiofrequency ablation versus resection for the treatment of early stage hepatocellular carcinoma: A multicenter Australian study. Scand J Gastroenterol 2015;50:567-76.
Hiraoka A, Kumada T, Michitaka K, Toyoda H, Tada T, Takaguchi K, et al.
Clinical features of hemodialysis patients treated for hepatocellular carcinoma: Comparison between resection and radiofrequency ablation. Mol Clin Oncol 2017;6:455-461.
Imai K, Beppu T, Chikamoto A, Doi K, Okabe H, Hayashi H, et al.
Comparison between hepatic resection and radiofrequency ablation as first-line treatment for solitary small-sized hepatocellular carcinoma of 3cm or less. Hepatol Res 2013;43:853-64.
Nishikawa H, Inuzuka T, Takeda H, Nakajima J, Matsuda F, Sakamoto A, et al.
Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma. BMC Gastroenterol 2011;11:143.
Desiderio J, Trastulli S, Pasquale R, Cavaliere D, Cirocchi R, Boselli C, et al.
Could radiofrequency ablation replace liver resection for small hepatocellular carcinoma in patients with compensated cirrhosis? A 5-year follow-up. Langenbecks Arch Surg 2013;398:55-62.
Parisi A, Desiderio J, Trastulli S, Castellani E, Pasquale R, Cirocchi R, et al.
Liver resection versus radiofrequency ablation in the treatment of cirrhotic patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2013;12:270-7.
Vivarelli M, Guglielmi A, Ruzzenente A, Cucchetti A, Bellusci R, Cordiano C, et al.
Surgical resection versus percutaneous radiofrequency ablation in the treatment of hepatocellular carcinoma on cirrhotic liver. Ann Surg 2004;240:102-7.
Kim GA, Shim JH, Kim MJ, Kim SY, Won HJ, Shin YM, et al.
Radiofrequency ablation as an alternative to hepatic resection for single small hepatocellular carcinomas. Br J Surg 2016;103:126-35.
Kim JM, Kang TW, Kwon CH, Joh JW, Ko JS, Park JB, et al.
Single hepatocellular carcinoma Ko JS, Park JB, tic resection: Liver resection or radiofrequency ablation? World J Gastroenterol 2014;20:4059-65.
Park EK, Kim HJ, Kim CY, Hur YH, Koh YS, Kim JC, et al.
A comparison between surgical resection and radiofrequency ablation in the treatment of hepatocellular carcinoma. Ann Surg Treat Res 2014;87:72-80.
Bu X, Ge Z, Ma J, Guo S, Wang Y, Liu J. Long-term efficacy of radiofrequency ablation compared to surgical resection for the treatment of small hepatocellular carcinoma. J BUON 2015;20:548-54.
Gao J, Wang SH, Ding XM, Sun WB, Li XL, Xin ZH, et al.
Radiofrequency ablation for single hepatocellular carcinoma 3 cm or less as first-line treatment. World J Gastroenterol 2015;21:5287-94.
Guo WX, Sun JX, Cheng YQ, Shi J, Li N, Xue J, et al.
Percutaneous radiofrequency ablation versus partial hepatectomy for small centrally located hepatocellular carcinoma. World J Surg 2013;37:602-7.
Guo WX, Zhai B, Lai EC, Li N, Shi J, Lau WY, et al.
Percutaneous radiofrequency ablation versus partial hepatectomy for multicentric small hepatocellular carcinomas: A nonrandomized comparative study. World J Surg 2010;34:2671-6.
Jiang L, Yan L, Wen T, Li B, Zeng Y, Yang J, et al.
Comparison of outcomes of hepatic resection and radiofrequency ablation for hepatocellular carcinoma patients with multifocal tumors meeting the Barcelona-Clinic Liver Cancer stage a classification. J Am Coll Surg 2015;221:951-61.
Lai EC, Tang CN. Radiofrequency ablation versus hepatic resection for hepatocellular carcinoma within the Milan criteria – A comparative study. Int J Surg 2013;11:77-80.
Peng ZW, Lin XJ, Zhang YJ, Liang HH, Guo RP, Shi M, et al.
Radiofrequency ablation versus hepatic resection for the treatment of hepatocellular carcinomas 2 cm or smaller: A retrospective comparative study. Radiology 2012;262:1022-33.
Peng ZW, Liu FR, Ye S, Xu L, Zhang YJ, Liang HH, et al.
Radiofrequency ablation versus open hepatic resection for elderly patients (>65 years) with very early or early hepatocellular carcinoma. Cancer 2013;119:3812-20.
Wang JH, Wang CC, Hung CH, Chen CL, Lu SN. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol 2012;56:412-8.
Wong KM, Yeh ML, Chuang SC, Wang LY, Lin ZY, Chen SC, et al.
Survival comparison between surgical resection and percutaneous radiofrequency ablation for patients in Barcelona Clinic Liver Cancer early stage hepatocellular carcinoma. Indian J Gastroenterol 2013;32:253-7.
Zhou Z, Lei J, Li B, Yan L, Wang W, Wei Y, et al.
Liver resection and radiofrequency ablation of very early hepatocellular carcinoma cases (single nodule <2 cm): A single-center study. Eur J Gastroenterol Hepatol 2014;26:339-44.
Ren ZG, Gan YH, Fan J, Chen Y, Wu ZQ, Qin LX, et al.
Treatment of postoperative recurrence of hepatocellular carcinoma with radiofrequency ablation comparing with repeated surgical resection. Zhonghua Wai Ke Za Zhi 2008;46:1614-6.
Sucandy I, Cheek S, Golas BJ, Tsung A, Geller DA, Marsh JW. Longterm survival outcomes of patients undergoing treatment with radiofrequency ablation for hepatocellular carcinoma and metastatic colorectal cancer liver tumors. HPB (Oxford) 2016;18:756-63.
Kariyama K, Wakuta A, Nishimura M, Kishida M, Oonishi A, Ohyama A, et al.
Percutaneous radiofrequency ablation for intermediate-stage hepatocellular carcinoma. Oncology 2015;89 Suppl 2:19-26.
Jiang K, Su M, Zhao X, Chen Y, Zhang W, Wang J, et al.
“One-off” complete radiofrequency ablation of hepatocellular carcinoma adjacent to the gallbladder by a novel laparoscopic technique without gallbladder isolation. Cell Biochem Biophys 2014;68:547-54.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]