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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 4  |  Page : 625-630

Efficacy comparison of radiofrequency ablation and hepatic resection for hepatocellular carcinoma: A meta-analysis


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 Publication13-Sep-2017

Correspondence Address:
Tao Jiang
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
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_406_17

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 > Abstract 

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 2018 Aug 16];13:625-30. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/625/214470


 > Introduction Top


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.[1] 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.[2],[3],[4] 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.[5] 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.[6] 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 Top


Study selection

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.

Data extraction

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.

Statistical 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 Top


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.[6],[7],[8]
Figure 1: Flow diagram for the selection of eligible studies

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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 [9] and Australia,[10] three in Japan,[11],[12],[13] Italy [14],[15],[16] and South Korea,[17],[18],[19] 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.[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30]
Table 1: Characteristics of the included studies

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Efficacy

Overall survival

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

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Figure 3: Funnel plot of comparison of radiofrequency ablation and hepatic resection group

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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

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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

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Disease-/recurrence-free survival

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

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Figure 7: Funnel plot of comparison of disease-free survival rates in the radiofrequency ablation group to those in the hepatic resection group

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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

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Figure 9: Funnel plot of comparison of recurrence-free survival rates in the radiofrequency ablation group to those in the hepatic resection group

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 > Discussion Top


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.[31],[32] 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.[11] 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.[15] 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.[27] 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.[33],[34]

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 Top


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

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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