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©2013 Baishideng Publishing Group Co.
World J Gastroenterol. Jul 14, 2013; 19(26): 4106-4118
Published online Jul 14, 2013. doi: 10.3748/wjg.v19.i26.4106
Published online Jul 14, 2013. doi: 10.3748/wjg.v19.i26.4106
Table 1 Proposed evidences and recommendations from international guidelines
Guidelines | Hepatic resection | Radiofrequency ablation |
EASL | Resection is the first-line treatment option for patients with solitary tumors and very well-preserved liver function, defined as normal bilirubin with either hepatic venous pressure gradient ≤ 10 mmHg or platelet count ≥ 100000 (evidence 2A; recommendation 1B) | Local ablation with radiofrequency or percutaneous ethanol injection is considered the standard of care for patients with BCLC 0-A tumors not suitable for surgery (evidence 2A; recommendation 1B) |
EORTC[9] | Additional indications for patients with multifocal tumors meeting Milan criteria ( ≤ 3 nodules ≤ 3 cm) or with mild portal hypertension not suitable for liver transplantation require prospective comparisons with loco-regional treatments. (evidence 3A; recommendation 2C) | In tumors < 2 cm, BCLC 0, Ethanol injection and radio-frequency ablation achieve complete responses in more than 90% of cases with good long-term outcome [evidence 1(i)A; recommendation 1C] |
AASLD[10] | Patients who have a single lesion can be offered surgical resection if they are non-cirrhotic or have cirrhosis but still have well preserved liver function, normal bilirubin and hepatic vein pressure gradient < 10 mmHg (recommendation 2) | Local ablation is safe and effective therapy for patients who cannot undergo resection, or as a bridge to transplantation (recommendation 2); Alcohol injection and radiofrequency are equally effective for tumors < 2 cm. However, the necrotic effect of radiofrequency ablation is more predictable in all tumor sizes and its efficacy is clearly superior to that of alcohol injection in larger tumors (recommendation 1) |
APASL[11] | Liver resection is a first-line curative treatment of solitary or multifocal HCC confined to the liver, anatomically resectable, and with satisfactory liver function reserve (evidence 2B, recommendation B) | Local ablation is an acceptable alternative to resection for small HCC (< 3 cm) in Child-Pugh A cirrhosis (evidence 2B, recommendation B); Local ablation is a first-line treatment of unresectable, small HCC with 3 or fewer nodules in Child-Pugh A or B cirrhosis (evidence 2B, recommendation B) |
Table 2 Summary of published articles that directly compared hepatic resection and radio-frequency ablation identified through literature search
Ref. | Study period | Type of study | NOS |
Feng et al[35] | 2005-2008 | RCT | - |
Peng et al[36] | 2003-2008 | Retrospective | 7 |
Wang et al[37] | 2002-2009 | Retrospective | 6 |
Ruzzenente et al[47] | 1995-2009 | Retrospective | 8 |
Nishikawa et al[42] | 2004-2010 | Retrospective | 7 |
Hung et al[38] | 2002-2007 | Retrospective | 7 |
Takayama et al[39] | 2000-2003 | Retrospective | 5 |
Huang et al[34] | 2003-2005 | RCT | - |
Ueno et al[41] | 2000-2005 | Retrospective | 7 |
Abu-Hilal et al[48] | 1991-2003 | Retrospective | 8 |
Guglielmi et al[43] | 1996-2006 | Retrospective | 7 |
Hiraoka et al[40] | 2000-2007 | Retrospective | 7 |
Hasegawa et al[46] | 2000-2003 | Survey | 6 |
Lupo et al[45] | 1999-2006 | Retrospective | 8 |
Chen et al[33] | 1999-2004 | RCT | - |
Ogihara et al[49] | 1995-2003 | Retrospective | 7 |
Montorsi et al[50] | 1997-2003 | Retrospective | 6 |
Hong et al[51] | 1999-2001 | Retrospective | 6 |
Vivarelli et al[44] | 1998-2002 | Retrospective | 5 |
Table 3 Characteristics of randomized controlled studies that compared hepatic resection vs radiofrequency ablation
Ref. | Liver function | Tumor features | Treatment | Study characteristics and main findings |
Chen et al[33] | Child-Pugh class AICG-R15 < 30%PLT > 40000/mm3 | Single < 5 cm | HR: 90RFA: 71 | 21% of patients randomized to RFA withdrew their consent. The 1-, 3-, and 4-year overall survival rates after RFA and surgery were 95.8%, 71.4%, 67.9% and 93.3%, 73.4%, 64.0%, respectively. The corresponding DFS rates were 85.9%, 64.1%, 46.4% and 86.6%, 69%, 51.6%, respectively. Statistically, there was no difference. The 5-year rates were not reported |
Single tumor ≤ 3 cm | HR: 42RFA: 37 | Authors stated that patient survival and DFS did not change in tumors < 3 cm but survival rates and P-values were not provided (only Kaplan-Meier curves were reported) | ||
Single 3.1-5.0 cm | HR: 48RFA: 34 | Authors stated that patient survival and DFS did not change in tumors between 3.1 and 5.0 cm but survival rates and P-values were not provided (only Kaplan-Meier curves were reported) | ||
Huang et al[34] | Child-Pugh class A/BICG-R15 < 20%PLT > 50000/mm3 | Single ≤ 5 cm or up to 3 nodules < 3 cm | HR: 115RFA: 115 | Despite randomization, RFA patients had higher prevalence of nodules ≤ 3 cm (P = 0.021). The 3- and 5-year survival rates for the RFA group and the HR group were 69.6%, 54.8% and 92.2%, 75.7%, respectively (P = 0.001). The corresponding RFS rates were 46.1%, 28.7% and 60.9%, 51.3%, respectively (P = 0.017) |
Single tumor ≤ 3 cm | HR: 45RFA: 57 | The 3- and 5-year survival rates for the RFA group and the HR group were 77.2%, 61.4% and 95.6%, 82.2%, respectively (P = 0.030). Neither DFS nor RFS for this subgroup were provided | ||
Single 3.1-5.0 cm | HR: 44RFA: 27 | The 3- and 5-year survival rates for the RFA group and the HR group were 66.7%, 51.5% and 95.5%, 72.3%, respectively (P = 0.046). Neither DFS nor RFS for this subgroup were provided | ||
Multifocal < 3 cm | HR: 26RFA: 31 | The 3- and 5-year survival rates for the RFA group and the HR group were 58.1%, 45.2% and 80.8%, 69.2%, respectively (P = 0.042). Neither DFS nor RFS for this subgroup were provided | ||
Feng et al[35] | Child-Pugh class A/BICG-R15 < 30%PLT > 50000/mm3 | Up to 2 nodules < 4 cm | HR: 84RFA: 84 | The 1- and 3-year survival rates for HR and RFA groups were 96.0%, 74.8% and 93.1%, 67.2%, respectively (P = 0.342). The corresponding RFS rates were 90.6%, 61.1% and 86.2%, 49.6%, respectively (P = 0.122). Results at 5-year not reported (or not reached). On the basis of this lack of evidence, the authors did not include treatment as a variable in multivariate analysis |
Table 4 Characteristics of observational studies that compared hepatic resection vs radiofrequency ablation
Ref. | Liver function | Tumor features | Treatment | Study characteristics and main findings |
Peng et al[36] | Child-Pugh class A | Single tumor ≤ 2 cm | HR: 74RFA: 71 | RFA patients showed lower prothrombin activity (P = 0.001) and lower platelet count (P = 0.010). Other features were similar between the two groups |
The 3-, and 5-year survival rates were 87.7% and 71.9%, respectively, after RFA and 70.9% and 62.1% after HR (P = 0.048). The corresponding RFS rates were 65.2% and 59.8% with RFA and 56.1%, and 51.3% after HR (P = 0.548) | ||||
Wang et al[37] | Child-Pugh class A and B | BCLC early stage | HR: 208RFA: 254 | Patient characteristics were considerably different between the two treatments. RFA patients were significantly older, anti-HCV+, in Child-Pugh class B, with lower platelet count, with smaller and multifocal tumors than HR patients (P = 0.001 in all cases) |
The 3- and 5-year survival rates were 87.8% and 77.2% for HR, and 73.5% and 57.4% for RFA (P = 0.001). The 3- and 5-year DFS rates were 59.9% and 50.8% for HR and 28.3% and 14.1% for RFA, respectively (P < 0.001) | ||||
BCLC early stage after PS match | HR: 208RFA: 208 | Patient characteristics were different between the two treatment arms. RFA patients were significantly older, anti-HCV+, in Child-Pugh class B, with lower platelet count, with smaller and multifocal tumors than HR patients (P = 0.001 in all cases). Patient and DFS rates not provided for this subgroup | ||
Single tumor < 2 cm | HR: 52RFA: 91 | Patient characteristics were different between the two treatment arms. RFA patients were significantly older, anti-HCV+, with lower platelet count than HR patients (P < 0.050). No Child-Pugh stratification was provided | ||
The 3- and 5-year survival rates were 98% and 91.5% for HR, and 80.3% and 72% for RFA (P = 0.073). The 3- and 5-year DFS rates were 62.1% and 40.7% for HR and 39.8% and 29.3% for RFA, respectively (P = 0.006) | ||||
Single tumor < 2 cm after PS match | HR: 52RFA: 52 | Patient characteristics seem similar between the two treatments. The 3- and 5-year survival rates were 98% and 91.5% for HR, and 82.8% and 82.8% for RFA, respectively (P = 0.269). The 3- and 5-year DFS rates were 62.1% and 40.7% for HR and 46.8% and 38.0% for RFA (P = 0.031) | ||
Ruzzenente et al[47] | Child-Pugh class A and B | Up to 3 tumors ≤ 6 cm after PS match | HR: 88RFA: 88 | Patient characteristics seem similar between the two treatments. The 3- and 5-year survival rates were 68.7% and 59.3% for HR, and 50.1% and 27.7% for RFA (P = 0.012). The 3- and 5-year DFS rates were 50.4% and 27.1% for HR and 30.2% and 18.6% for RFA, respectively (P = 0.001) |
Child-Pugh class A and B | Single tumor < 5 cm | HR: 45RFA: 40 | The 3- and 5-year survival rates were 66.1% and 54.5% for HR, and 63.7% and 43.8% for RFA (P = 0.633). The 3- and 5-year DFS rates were 42.4% and 22.6% for HR and 30.7% and 23.0% for RFA, respectively (P = 0.644). Patient and disease-free survival after HR were significantly superior to RFA, in patients with tumors ≥ 5 cm | |
Further stratifications lead to very small groups (n < 10) | ||||
Nishikawa et al[42] | Child-Pugh class A and B | Single tumor ≤ 3 cm | HR: 78RFA: 92 | RFA patients had smaller tumors (P = 0.001) and lower platelet count (P = 0.004) in comparison to HR patients |
The 5-year overall survival rates after RFA and HR were 63.1% and 74.6%, respectively (P = 0.259). The corresponding RFS rates were 18.0% and 26.0%, respectively (P = 0.324). In the multivariate analysis treatment was not an independent risk factor for overall and RFS | ||||
Hung et al[38] | Child-Pugh class A and B | Up to 3 tumors ≤ 5 cm | HR: 229RFA: 190 | RFA patients were significantly older, anti-HCV+, with lower albumin and platelet count (P < 0.050) in comparison to HR patients |
The 3- and 5-year survival rates were 88.2% and 79.3% for HR, and 77.3% and 67.4% for RFA, respectively (P = 0.009). The 3- and 5-year RFS rates were 56.1% and 40.9% for HR and 29.0% and 20.5% for RFA (P = 0.001) | ||||
Up to 3 tumors ≤ 5 cm after PS match | HR: 84RFA: 84 | Patient characteristics seem similar between the two treatments | ||
Patient and DFS rates not provided but only reported in Kaplan-Meier graphs. For patient survival no difference was found (P = 0.519); RFS was significantly worse after RFA (P < 0.001) | ||||
Single tumor < 2 cm | HR: 50RFA: 66 | RFA patients were significantly older, anti-HCV+, with lower albumin and platelet count, higher bilirubin, AST and ICG-R15 and with smaller tumors (P = 0.001) in comparison to HR patients | ||
The 3- and 5-year survival rates were 91.1% and 84.6% for HR, and 86.5% and 77.8% for RFA, respectively (P = 0.358). The 3- and 5-year RFS rates were 42.6% and 21.8% for HR and 59.5% and 45.2% for RFA (P = 0.104) | ||||
Takayama et al[39] | Child-Pugh class A and B | Single tumor ≤ 2 cm | HR: 1235RFA: 1315 | Data from the Liver Cancer Study Group of Japan database. Results were reported in the form of brief communication. RFA patients were significantly more frequently in Child-Pugh class B, had higher ICG-R15 and smaller tumor size (P = 0.001 in all cases) in comparison to HR patients |
The 1- and 2-year survival rates were 98% and 94% for HR, and 99% and 95% for RFA, respectively (P = 0.280). The 1- and 2-year DFS rates were 91% and 70% for HR and 84% and 58% for RFA, respectively (P = 0.001) | ||||
Multivariate analysis on DFS confirmed alpha-fetoprotein, therapy and Child-Pugh class as independent factors | ||||
Ueno et al[41] | Child-Pugh class A and B | BCLC early stage | HR: 123RFA: 155 | RFA patients were significantly more frequently in Liver Damage class B or C, had higher ICG-R15, MELD score and smaller tumor size (P = 0.001 in all cases) in comparison to HR patients |
The 3- and 5-year survival rates were 92% and 80% for HR, and 92% and 63% for RFA, respectively (P = 0.06). The 3- and 5-year DFS rates were 47% and 38% for HR and 36% and 20% for RFA (P = 0.02) | ||||
Single tumor ≤ 3 cm | HR: 78RFA: 92 | The 3- and 5-year survival rates were 95% and 95% for HR, and 90% and 60% for RFA, respectively (P = 0.01). The 3- and 5-year DFS rates were 56% and 44% for HR and 37% and 11% for RFA (P = 0.02) | ||
Single tumor 3.1-5.0 cm | HR: 32RFA: 9 | The 3- and 5-year survival rates were 92% and 72% for HR, and 73% and 73% for RFA, respectively (P = 0.15). The 3- and 5-year DFS rates were 33% and 25% for HR and 14% and 14% for RFA (P = 0.12) | ||
2 or 3 nodules ≤ 3 cm | HR: 13RFA: 54 | The 3- and 5-year survival rates were 67% and not reached for HR, and 93% and 63% for RFA, respectively (P = 0.002). The 3- and 5-year DFS rates were 29% and not reached for HR and 35% and 22% for RFA (P = 0.59) | ||
Abu-Hilal et al[48] | Child-Pugh class A and B | Single tumor ≤ 5 cm | HR: 34 | This was a matched analysis for age, sex, tumor size, and Child-Pugh grade |
RFA: 34 | The 5-year survival was 56% for HR, and 57% for RFA (P = 0.302). The 5-year DFS was 28% for HR and 21% for RFA (P = 0.028) | |||
Guglielmi et al[43] | Child-Pugh class A and B | Up to 3 tumors ≤ 6 cm | HR: 91RFA: 109 | RFA patients were significantly older, belonged more frequently to Child-Pugh class B and more frequently had multinodular tumors (P = 0.010) in comparison to HR patients |
The 3- and 5-year survival rates were 64% and 48% for HR, and 42% and 20% for RFA, respectively (P = 0.010). The 3- and 5-year DFS rates were 56% and 27% for HR and 22% and 22% for RFA (P = 0.001) | ||||
Superiority of HR was confined to patients in Child-Pugh class A. Further stratifications resulted in groups of patients not large enough (n < 10) to obtain realistic comparisons | ||||
Type of treatment was significantly related to survival and DFS at multivariate analyses | ||||
Child-Pugh class A | Single tumor ≤ 3 cm | HR: 20RFA: 11 | The 3- and 5-year survival rates were 93% and 71% for HR, and 50% and not reached for RFA, respectively (P = 0.060) | |
Child-Pugh class A | Single tumor > 3 cm | HR: 33RFA: 23 | The 3- and 5-year survival rates were 64% and 55% for HR, and 63% and 45% for RFA, respectively (P = 0.700) | |
Hiraoka et al[40] | Child-Pugh class A and B | Single tumor ≤ 3 cm | HR: 59RFA: 105 | RFA patients belonged more frequently to Child-Pugh class B (P = 0.011), more frequently had tumors < 2 cm (P = 0.001), and had worse ICG-R15 (P = 0.026) in comparison to HR patients |
The 3- and 5-year survival rates were 91.4% and 59.4% for HR, and 87.8% and 59.3% for RFA, respectively (P = NS). The 3- and 5-year DFS rates were 64.3% and 22.4% for HR and 58.7% and 24.6% for RFA (P = NS) | ||||
No multivariate analysis provided | ||||
Hasegawa et al[46] | Child-Pugh class A and B | Up to 3 tumors ≤ 3 cm | HR: 2857RFA: 3022 | Data were analyzed together with a population of 1306 patients submitted to percutaneous ethanol injection. RFA patients were significantly older, belonged more frequently to Child-Pugh class B, had lower serum albumin, higher bilirubin, worse ICG-R15 and more frequently had multinodular and smaller tumors (P < 0.001 in all cases) in comparison to HR patients |
Results were limited to 24 mo. The 1- and 2-year survival rates were 98.3% and 94.5% for HR, and 98.5% and 93.0% for RFA, respectively (P = 0.640) | ||||
The 1- and 2-year recurrence rates were 17.0% and 35.5% for HR and 26.0% and 55.4% for RFA (P < 0.001) | ||||
At multivariate analysis, type of treatment did not affect overall survival but affected recurrence rate | ||||
Lupo et al[45] | Child-Pugh class A and B | Single tumor 3-5 cm | HR: 42RFA: 60 | The groups were similar in terms of median age, Child-Pugh score and tumor size |
The 3- and 5-year survival rates were 57% and 43% for HR, and 53% and 32% for RFA, respectively (P = 0.824). The 3- and 5-year DFS rates were 35% and 14% for HR and 18% and 0% for RFA (P = 0.283) | ||||
No multivariate analyses were performed | ||||
Ogihara et al[49] | Child-Pugh class A and B | Single tumor without size limit | HR: 47RFA: 40 | RFA patients were significantly older, belonged more frequently to Child-Pugh class B and had smaller tumors (P < 0.001 in all cases) in comparison to HR patients |
The 3- and 5-year survival rates were 65% and 31% for HR, and 58% and 39% for RFA, respectively (P = NS). DFS not provided. No multivariate analysis was provided | ||||
Child-Pugh class A and B | Single tumor ≤ 5 cm | HR: 18RFA: 26 | In these subgroups, RFA patients were still significantly older and belonged more frequently to Child-Pugh class B (P < 0.050) in comparison to HR patients | |
The 3- and 5-year survival rates were 64% and 21% for HR, and 53% and 32% for RFA, respectively (P = NS). The 3- and 5-year DFS rates were 37% and 37% for HR and 31% and 23% for RFA (P = NS) | ||||
Results did not change in single tumors > 5 cm | ||||
Montorsi et al[50] | Child-Pugh class A and B | Single tumor ≤ 5 cm | HR: 40RFA: 58 | All RFA were performed with laparoscopic approach. RFA patients had significantly worse INR and higher AST (P < 0.050). A trend toward higher bilirubin, lower platelet count and higher ALT was also reported (P < 0.10) |
The 3- and 4-year survival rates were 73% and 61% for HR, and 61% and 42% for RFA, respectively (P = 0.139). The RFS rates were not reported and only plotted in a Kaplan-Meier curve reporting a P = 0.024. Five-year rates not reported. Multivariate analysis on survival did not include the primary exposure variable (HR vs RFA) | ||||
Hong et al[51] | Child-Pugh class A | Single tumor ≤ 4 cm | HR: 93RFA: 55 | RFA patients were significantly older (P < 0.001) but the other characteristics reported were not statistically different between the two groups |
The 1- and 3-year survival rates were 97.9% and 83.9% for HR, and 100% and 72.7% for RFA, respectively (P = 0.24). The 1- and 3-year RFS rates were 75.9% and 54.7% for HR and 74.1% and 40.2% for RFA (P = 0.54). Five-year rates not reported. Results did not change when patients were stratified by AJCC or CLIP stages | ||||
No multivariate analyses were performed | ||||
Vivarelli et al[44] | Child-Pugh class A and B | No inclusion criteria specified | HR: 79RFA: 79 | RFA patients belonged more frequently to Child-Pugh class B and more frequently had multinodular tumors (P < 0.001 in both cases) |
The 1- and 3-year survival rates were 83% and 65% for HR, and 78% and 33% for RFA, respectively (P = 0.002). The 1- and 3-year DFS rates were 79% and 50% for HR and 60% and 20% for RFA (P = 0.001). Five-year rates not reported. No multivariate analyses were performed | ||||
Child-Pugh class A and B | Single tumor ≤ 3 cm | HR: 21RFA: 22 | The 1- and 3-year survival rates were 89% and 79% for HR, and 89% and 50% for RFA, respectively (P = NS). The 1- and 3-year DFS rates were 84% and 67% for HR and 70% and 34% for RFA (P = NS). Five-year rates not reported | |
Child-Pugh class A and B | Single tumor > 3 cm | HR: 58RFA: 57 | The 1- and 3-year survival rates were 81% and 59% for HR, and 74% and 24% for RFA, respectively (P = 0.007). The 1- and 3-year DFS rates were 77% and 43% for HR and 56% and 12% for RFA (P = 0.003). Five-year rates not reported. These differences were confirmed when the analyses were confined to Child-Pugh class A patients |
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Citation: Cucchetti A, Piscaglia F, Cescon M, Ercolani G, Pinna AD. Systematic review of surgical resection
vs radiofrequency ablation for hepatocellular carcinoma. World J Gastroenterol 2013; 19(26): 4106-4118 - URL: https://www.wjgnet.com/1007-9327/full/v19/i26/4106.htm
- DOI: https://dx.doi.org/10.3748/wjg.v19.i26.4106