Systematic review of surgical resection vs radiofrequency ablation for hepatocellular carcinoma

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

HR: Hepatic resection; RFA: Radiofrequency ablation; RFS: Recurrence-free survival; DFS: disease-free survival; PS: Propensity score; AST: Aspartate aminotransferase; NS: Not significant; BCLC: Barcelona Clinic Liver Cancer; HCV: Hepatitis C virus; AJCC: American Joint Committee on Cancer; CLIP: Cancer of the Liver Italian Program; MELD: Model for end-stage liver disease.