Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: a systematic review and meta-analysis

Figures & data

Figure 1 PRISMA flow diagram.Abbreviations: PRISM, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SLR, systematic literature review; MWA, microwave ablation; RFA, radiofrequency ablation.

Table 1 Study and baseline characteristics for studies included in the meta-analysis

First author	Year	Study design	Region	Population	Intervention	Comparator	Patients (N)		Mean age	Male (%)	Follow-up duration (months)
							MWA	RFA			MWA	RFA
Abdelaziz	2014	RCT	Egypt	HCC	MWA	RFA	66	45	54.90	71	NR	NR
Chinnaratha	2015	Retrospective cohort	Australia	HCC	MWA	RFA	25	101	62.10	78	14	14
Cillo	2014	Prospective observational; propensity score matched	Italy	HCC	MWA	RFA	28	28	64.00	82	24	NR
Correa-Gallego	2014	Retrospective matched cohort	USA	Metastatic	MWA	RFA	67	67	55.50	NR	18	31
Di Vece	2014	RCT	Italy	HCC/Metastatic	MWA	RFA	20	20	61.00	73	NR	NR
Ding	2013	Retrospective cohort	China	HCC	MWA	RFA	113	85	58.82	77	18	28
Ginsburg	2015	Retrospective cohort	USA	HCC	MWA+TACE	RFA+TACE	51	38	65.29	38	28	56
Hompes	2010	Retrospective cohort case-matched	Belgium	Metastatic	MWA	RFA	6	13	59.89	47	6	NR
Kuang^a	2011	Prospective observational	China	HCC	MWA	RFA	19	31	55.00	94	45	45
Lee	2017	Retrospective cohort case-matched	China	HCC	MWA	RFA	26	47	59.60	71	48	53
Liu	2013	Retrospective cohort	China	Metastatic	MWA	RFA	35	54	53.20	61	32	32
Ohmoto	2009	Retrospective cohort	Japan	HCC	MWA	RFA	49	34	65.23	80	34	26
Potretzke	2016	Retrospective cohort	USA	HCC	MWA	RFA	99	55	61.36	79	24	31
Qian	2012	Prospective observational	China	HCC	MWA	RFA	22	20	53.90	93	5	5
Sakaguchi	2009	Retrospective cohort	Japan	HCC	MWA	RFA	142	249	65.35	71	NR	NR
Santambrogio	2017	Retrospective cohort	Italy	HCC	MWA	RFA	60	94	69.39	73	27	27
Shady	2017	Retrospective cohort	USA	Metastatic	MWA	RFA	48	62	NR	66	29	56
Sheta^a	2016	RCT	Egypt	HCC	MWA+TACE	RFA+TACE	10	20	NR	NR	6	6
Simo	2011	Retrospective cohort	USA	HCC	MWA	RFA	13	22	58.61	74	7	19
Thornton	2017	Retrospective cohort	USA	HCC	MWA+TAE/TACE	RFA+TAE/TACE	20	15	64.63	83	14	18
van Tilborg	2016	Retrospective cohort	Netherlands	Metastatic	MWA	RFA	15	96	61.27	65	31	NR
Vasnani	2016	Retrospective cohort	USA	HCC	MWA+TACE	RFA+TACE	31	11	58.31	64	NR	NR
Vogl	2015	Retrospective cohort	Egypt	HCC	MWA	RFA	28	25	58.58	79	NR	NR
Xu	2017	Retrospective cohort	China	HCC	MWA	RFA	301	159	54.13	80	53	62
Yang	2017	Retrospective cohort	China	Metastatic	MWA	RFA	71	108	50.40	65	39	39
Yin	2009	Prospective observational	China	HCC	MWA	RFA	50	59	53.00	87	22	22
Yu	2017	RCT	China	HCC	MWA	RFA	203	200	NR	NR	35	35
Zhang	2013	Prospective observational	China	HCC	MWA	RFA	77	78	54.00	85	25	26

Note: ^aThree-armed study.

Abbreviations: MWA, microwave ablation; NR, not reported; RCT, randomized control trial; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; TAE, transarterial embolization.

Figure 2 Forest plot of random-effects meta-analysis results for LTP (P=0.02), stratified by RCTs (P=0.01) versus observational studies (P=0.07).

Abbreviations: LTP, local tumor progression; RCT, randomized control trial.

Figure 3 Weighted one-, three-, and five-year OS and DFS for MWA and RFA.

Notes: The error bars represent the 95% CIs for each estimate.

Abbreviations: DFS, disease-free survival; MWA, microwave ablation; OS, overall survival; RFA, radiofrequency ablation.

Figure 4 Summary of meta-analyses.

Abbreviations: DFS, disease-free survival; EHM, extrahepatic metastasis; IDL, intrahepatic de novo lesions; OS, overall survival.

Figure 5 Funnel plot assessing publication bias for LTP in 18 studies. Red points indicate RCTs and blue points indicate observational studies.

Abbreviation: LTP, local tumor progression; MWA, microwave ablation; RCT, randomized control trial; RFA, radiofrequency ablation.

Figure S1 Methodological quality assessment of RCTs using the Cochrane RoB tool.

Abbreviations: RCT, randomized control trial; RoB, Risk of Bias.

Figure S2 Forest plot of random effects meta-analysis results for technique efficacy (P=0.25), stratified by RCTs (P=0.23) versus observational studies (P=0.34).

Abbreviation: RCT, randomized control trial.

Figure S3 Forest plot of random effects meta-analysis results for one-year OS (P=0.80), stratified by RCTs (P=0.43) versus observational studies (P=0.57).

Abbreviations: OS, overall survival; RCT, randomized control trial.

Figure S4 Forest plot of random effects meta-analysis results for three-year OS (P=0.40), stratified by RCTs (P=0.94) versus observational studies (P=0.38).

Abbreviations: OS, overall survival; RCT, randomized control trial.

Figure S5 Forest plot of random effects meta-analysis results for five-year OS (P=0.60), stratified by RCTs (P=0.27) versus observational studies (P=0.32).

Abbreviations: OS, overall survival; RCT, randomized control trial.

Figure S6 Forest plot of random effects meta-analysis results for one-year DFS (P=0.93), stratified by RCTs (P=0.97) versus observational studies (P=0.67).

Abbreviations: DFS, disease-free survival; RCT, randomized control trial.

Figure S7 Forest plot of random effects meta-analysis results for three-year DFS (P=0.27), stratified by RCTs (P=0.34) observational studies (P=0.73).

Abbreviations: DFS, disease-free survival; RCT, randomized control trial.

Figure S8 Forest plot of random effects meta-analysis results for five-year DFS (P=0.86), stratified by RCTs (P=0.006) versus observational studies (P=0.045).

Abbreviations: DFS, disease-free survival; RCT, randomized control trial.

Figure S9 Forest plot of random effects meta-analysis results for EHM (P=0.056).

Abbreviation: EHM, extrahepatic metastasis.

Figure S10 Forest plot of random effects meta-analysis results for IDL (P=0.40), stratified by RCTs (P=0.034) versus observational studies (P=0.83).

Abbreviations: IDL, intrahepatic de novo lesions; RCT, randomized control trial.

Figure S11 Forest plot of random effects meta-analysis results for LOS (P=0.26).

Abbreviation: LOS, length of stay.

Figure S12 Forest plot of random effects meta-analysis results for complications (P=0.75), stratified by RCTs (P=0.68) versus observational studies (P=0.60).

Abbreviation: RCT, randomized control trial.

Figure S13 Publication Bias Assessments.

Notes: Funnel plots assessing publication bias for (A) technique efficacy (n=18), (B) one-year OS (n=15), (C) three-year OS (n=14), and (D) complications (n=16). Red points indicate RCTs and blue points indicate observational studies.

Abbreviations: MWA, microwave ablation; OS, overall survival; RCT, randomized control trial; RFA, radiofrequency ablation.

Table 2 Summary of analyses for MWA compared with RFA

Outcome	Number of studies included in meta-analysis	Summary effect^a (95% CI); P value	Heterogeneity (I^2 value)
LTP	18	0.70 (0.53, 0.94); P=0.02	43%
Technique efficacy	18	1.01 (0.99, 1.03); P=0.25	13%
IDL	9	0.93 (0.79, 1.10); P=0.40	43%
EHM	2	0.66 (0.43, 1.01); P=0.06	0%
OS (1-Year)	16	1.00 (0.98, 1.02); P=0.80	26%
OS (3-Year)	14	1.03 (0.97, 1.09); P=0.40	37%
OS (5-Year)	9	1.03 (0.93, 1.13); P=0.60	33%
DFS (1-Year)	8	1.00 (0.96, 1.04); P=0.93	13%
DFS (3-Year)	7	1.05 (0.96, 1.14); P=0.27	0%
DFS (5-Year)	5	0.97 (0.71, 1.33); P=0.86	71%
Length of hospital stay (days)	7	−0.40 (−1.09, 0.29); P=0.26	80%
Complications	16	1.05 (0.77, 1.45); P=0.75	0%

Notes: ^aRR for MWA versus RFA for all outcomes except length of hospital stay, which is reported as the WMD. Point estimates and CIs were calculated using a random-effects model.

Abbreviations: DFS, disease-free survival; EHM, extrahepatic metastasis; IDL, intrahepatic de novo lesions; LTP, local tumor progression; MWA, microwave ablation; OS, overall survival; RFA, radiofrequency ablation; RR, risk ratio; WMD, weighted mean difference.

Table 3 Summary of subgroup analyses for MWA compared with RFA

Subgroup	LTP [RR (95% CI); P value; studies (N); I^2]	OS (1-Year) [RR (95% CI); P value; studies (N); I^2]	Complications [RR (95% CI); P value; studies (N); I^2]	Technique efficacy [RR (95% CI); P value; studies (N); I^2]
Tumor size
<2.5 cm	0.72 (0.41,1.29); P=0.27; 8; 67%	0.98 (0.95,1.01); P=0.26; 9; 61%	1.27 (0.84,1.91); P=0.26; 7; 0%	1.01 (0.98,1.04); P=0.53; 6; 14%
≥2.5 cm	0.63 (0.49,0.82); P=0.001; 8; 0%	1.06 (0.97,1.16); P=0.22; 6; 53%	0.71 (0.42,1.23); P=0.22; 7; 0%	1.02 (0.97,1.08); P=0.38; 10; 35%
Type of tumor
HCC	0.67 (0.54,0.82); P<0.001; 14; 0%	1.00 (0.98,1.02); P=0.87; 13; 19%	0.91 (0.62,1.33); P=0.62; 12; 0%	1.01 (0.99,1.02); P=0.41; 14; 2%
Liver metastasis	0.71 (0.19,2.67); P=0.61; 4; 78%	0.90 (0.82,0.99); P=0.04; 3; 0%	1.49 (0.83,2.66); P=0.18; 4; 0%	1.03 (0.99,1.08); P=0.13; 4; 0%
Intervention and comparator
MWA and RFA	0.72 (0.54,0.96); P=0.02; 16; 44%	1.00 (0.98,1.02); P=0.80; 15; 31%	1.06 (0.75,1.51); P=0.74; 13; 3%	1.01 (0.99,1.04); P=0.22; 14; 30%
MWA+TACE and RFA+TACE	0.29 (0.02,3.66); P=0.34; 2; 49%	Too few studies (<2) to inform	0.94 (0.36,2.46); P=0.90; 3; 0%	0.99 (0.89,1.10); P=0.85; 4; 2%
MWA frequency
2450 MHz	0.67 (0.53,0.84); P<0.001; 13; 0%	1.00 (0.97,1.03); P=0.94; 10; 34%	0.82 (0.54,1.24); P=0.345; 12; 0%	1.03 (0.99,1.07); P=0.13; 12; 42%
915 MHz	1.79 (1.14,2.81); P=0.01; 3; 0%	0.92 (0.78,1.08); P=0.31; 2; 9%	2.04 (0.95,4.38); P=0.07; 2; 0%	0.96 (0.86,1.06); P=0.41; 4; 0%

Abbreviations: HCC, hepatocellular carcinoma; MWA, microwave ablation; RFA, radiofrequency ablation; RR, risk ratio; TACE, transarterial chemoembolization.

Table 4 Summary of sensitivity analyses for MWA compared with RFA

	LTP	OS (1-Year)	OS (3-Year)	OS (5-Year)	DFS (1-Year)	DFS (3-Year)	DFS (5-Year)	Technique efficacy	EHM	IDL	LOS	Comp.
Primary analysis	0.70 (0.53,0.94); P=0.02; 18; 43%	1.00 (0.98,1.02); P=0.80; 16; 26%	1.03 (0.97,1.09); P=0.40; 14; 37%	1.03 (0.93,1.13); P=0.60; 9; 33%	1.00 (0.96,1.04); P=0.93; 8; 13%	1.05 (0.96,1.14); P=0.27; 7; 0%	0.97 (0.71,1.33); P=0.86; 5; 71%	1.01 (0.99,1.03); P=0.25; 18; 13%	0.66 (0.43,1.01); P=0.06; 2; 0%	0.93 (0.79,1.10); P=0.40; 9; 43%	−0.40 (−1.09,0.29); P=0.26; 7; 80%	1.05 (0.77,1.45); P=0.75; 16; 0%
Sensitivity analysis
Fixed effects	0.71 (0.59,0.85); P<0.001; 18; 43%	0.99 (0.97,1.02); P=0.59; 16; 26%	1.03 (0.98,1.08); P=0.20; 14; 37%	1.02 (0.95,1.09); P=0.65; 9; 33%	0.98 (0.94,1.03); P=0.49; 8; 13%	1.03 (0.94,1.12); P=0.50; 7; 0%	0.99 (0.86,1.14); P=0.90; 5; 71%	1.02 (1.00,1.05); P=0.04; 18; 25%	0.64 (0.42,0.99); P<0.05; 2; 0%	0.91 (0.82,1.00); P=0.05; 9; 43%	−0.27 (−0.54,0.00); P<0.05; 7; 80%	1.01 (0.75,1.38); P=0.93; 16; 0%
Exclusion of studies with poor quality^a	0.72 (0.53,0.97); P=0.03; 15; 49%	1.00 (0.98,1.01); P=0.74; 14; 16%	1.03 (0.96,1.09); P=0.45; 13; 41%	1.03 (0.93,1.13); P=0.60; 9; 33%	1.00 (0.96,1.04); P=0.93; 8; 13%	1.05 (0.96,1.14); P=0.27; 7; 0%	0.97 (0.71,1.33); P=0.86; 5; 71%	1.01 (0.99,1.03); P=0.30; 16; 21%	0.66 (0.43,1.01); P=0.06; 2; 0%	0.95 (0.80,1.12); P=0.52; 8; 46%	−0.40 (−1.09,0.29); P=0.26; 7; 80%	1.11 (0.80,1.54); P=0.52; 15; 0%
Exclusion of studies involving open surgery^b	0.64 (0.52,0.80); P<0.001; 14; 0%	1.00 (0.98,1.02); P=0.82; 12; 30%	1.01 (0.95,1.07); P=0.77; 10; 36%	1.00 (0.93,1.07); P=0.90; 6; 0%	1.00 (0.96,1.05); P=0.82; 7; 11%	1.04 (0.96,1.13); P=0.33; 6; 1%	0.96 (0.68,1.36); P=0.84; 4; 78%	1.01 (0.99,1.03); P=0.39; 14; 15%	Too few studies (<2) to inform	0.94 (0.77,1.16); P=0.56; 7; 55%	−0.45 (−1.21,0.31); P=0.25; 6; 83%	1.05 (0.72,1.53); P=0.79; 11; 0%

Notes: Table reports the effect estimate (RR for all outcomes except hospital LOS, which is presented as the WMD); 95% CIs; P value; number of studies; and heterogeneity (I² value). A random-effects model was applied if not specified. ^aExcludes Abdelaziz (2014), Hompes (2010), and Vogl (2015). ^bExcludes Correa-Gallego (2014), Lee (2017), and van Tilborg (2016).

Abbreviations: Comp., complications; DFS, disease-free survival; EHM, extrahepatic metastases; IDL, intrahepatic de novo lesions; LOS, length of stay; LTP, local tumor progression; OS, overall survival; RR, risk ratio; WMD, weighted mean difference.

Table S1 Summary of patient retreatment after initial thermal ablation with MWA or RFA

First Author	Year	Study Design	Region	Population	Intervention	Comparator	Retreatment Methods	Number of Retreated Patients
Abdelaziz, A	2014	RCT	Egypt	HCC	MWA	RFA	-	-
Chinnaratha, MA	2015	Retrospective cohort	Australia	HCC	MWA	RFA	Repeat thermal ablation until complete radiological ablation.	-
Cillo, U	2014	Prospective observational; propensity score matched	Italy	HCC	MWA	RFA	-	-
Correa-Gallego, C	2014	Retrospective matched cohort	USA	Metastatic	MWA	RFA	-	-
Di Vece, F	2014	RCT	Italy	HCC/Metastatic	MWA	RFA	-	-
Ding, J	2013	Retrospective cohort	China	HCC	MWA	RFA	-	-
Ginsburg, M	2015	Retrospective cohort	USA	HCC	MWA+TACE	RFA+TACE	-	-
Hompes, R	2010	Retrospective cohort case-matched	Belgium	Metastatic	MWA	RFA	-	-
Kuang, M^a	2011	Prospective observational	China	HCC	MWA	RFA	Repeat ablation with initially received treatment for cases with late failure	1 MWA and 1 RFA patient treated with resection or TACE
Lee, KF	2017	Retrospective cohort case-matched	China	HCC	MWA	RFA	Patients with residual tumors were retreated	Patients received RFA (n=2) or TACE (n=2)
Liu, Y	2013	Retrospective cohort	China	Metastatic	MWA	RFA	Post ablation systemic chemotherapy	72 patients (34 colorectal mets, 38 others) received chemotherapy
Ohmoto, K	2009	Retrospective cohort	Japan	HCC	MWA	RFA	Additional MWA or RFA was performed whenever possible on detection of recurrence	-
Potretzke, TA	2016	Retrospective cohort	USA	HCC	MWA	RFA	Liver transplants	18 RFA and 20 MWA patients received transplants
Qian, GJ	2012	Prospective observational	China	HCC	MWA	RFA	Additional MWA or RFA was performed if complete ablation was not achieved	1 RFA and 1 MWA patient received repeat ablation
Sakaguchi, H	2009	Retrospective cohort	Japan	HCC	MWA	RFA	-	-
Santambrogio, R	2017	Retrospective cohort	Italy	HCC	MWA	RFA	Additional ablation or TACE for incomplete local response	-
Shady, W	2017	Retrospective cohort	USA	Metastatic	MWA	RFA	-	-
Sheta, E^a	2016	RCT	Egypt	HCC	MWA+TACE	RFA+TACE	-	-
Simo, KA	2011	Retrospective cohort	USA	HCC	MWA	RFA	Liver transplant post ablation	2 MWA and 5 RFA received liver transplants.
Thornton, LM	2017	Retrospective cohort	USA	HCC	MWA+TAE/TACE	RFA+TAE/TACE	Alternative treatment for field progression or multifocal disease	Alternate treatment received by 2 RFA and 4 MWA patients. 2 RFA patients and 5 MWA patients received transplants.
van Tilborg, AA	2016	Retrospective cohort	Netherlands	Metastatic	MWA	RFA	Retreatment or additional treatment for recurrence	Successful retreatments. RFA patients: 9 re-RFA, 3 MWA, 2 resection, 1 stereotactic radiotherapy. MWA patients: 5 re-MWA, 3 RFA, 2 resection
Vasnani, R	2016	Retrospective cohort	USA	HCC	MWA+TACE	RFA+TACE	Retreatment for patients without complete response with initial combination. Liver transplantation.	4 RFA patients and 9 MWA patients had repeat treatment. 1 RFA patient had liver transplant and 8 MWA patients had liver transplant before follow-up imaging. 6 MWA patients had LT before complete response
Vogl, TJ	2015	Retrospective cohort	Egypt	HCC	MWA	RFA	-	-
Xu, Y	2017	Retrospective cohort	China	HCC	MWA	RFA	Retreatment for LTP and distant recurrence based on disease stage	MWA LTP patients n=29: 27 re-MWA, 4 resection. RFA LTP patients n=16: 14 re-RFA, 2 resection. MWA distant recurrence patients n=122: 91 re-MWA, 18 TACE, 11 resection, and 2 radiation therapy. RFA distant recurrence patients n=76: 58 re-RFA, 9 TACE, 8 resection, and 1 radiation therapy.
Yang, B	2017	Retrospective cohort	China	Metastatic	MWA	RFA	Repeat ablation or chemotherapy for patients without complete response	-
Yin, XY	2009	Prospective observational	China	HCC	MWA	RFA	Retreatment of local and distant recurrence with RFA or MWA if applicable	12 RFA patients and 4 MWA patients received repeat ablation
Yu, J	2017	RCT	China	HCC	MWA	RFA	-	-
Zhang, L	2013	Prospective observational	China	HCC	MWA	RFA	Retreatment with MWA or RFA for incomplete ablation	15 RFA and 14 MWA patients received repeat ablation

Abbreviations: LTP, local tumor progression; MWA, microwave ablation; -, not reported; RCT, randomized control trial; RFA, radiofrequency ablation; TACE; transarterial chemoembolization; TAE; transarterial embolization.

Table S2 Methodological quality assessment of RCTs using the Cochrane RoB tool

Study	Random Sequence Generation	Allocation Concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Abdelaziz 2014	Low	Unclear	Low	Low	High	Unclear	Low
Di Vece 2014	Low	Low	Low	Low	Low	Unclear	Low
Sheta 2016	Unclear	Unclear	Low	Low	Low	Unclear	Low
Yu 2017	Unclear	Unclear	Low	Low	Low	Unclear	Low

Abbreviations: RoB, risk of bias; RCT, randomized control trial.

Table S3 Methodological quality assessment of observational studies using the NOS scale^a

Study	Representativeness of Exposed Cohort	Selection of the Non-Exposed Cohort	Ascertainment of Exposure	Demonstration that outcome of interest was not present at the start of the study	Comparability of the cohorts on the basis of design or analysis	Assessment of outcome	Was the follow-up long enough for outcomes to occur?	Adequacy of follow-up of cohorts	Total
Chinnaratha 2015	*	*	*	*	**	*	*	*	9
Cillo 2014	*	*	*	*	**	*	*	*	9
Correa-Gallego 2014	*	*	*	*	**	*	*	*	9
Ding 2013	*	*	*	*	**	*	*	*	9
Ginsburg 2015	*	*	*	*	**	*	*	*	9
Hompes 2010	*	*	*	*	*	*		*	7
Kuang 2011	*	*	*	*	**	*	*	*	9
Lee 2017	*	*	*	*	*	*	*	*	8
Liu 2013	*	*	*	*	**	*	*	*	9
Ohmoto 2009	*	*	*	*	**	*	*	*	9
Potretzke 2016	*	*	*	*	*	*	*	*	8
Qian 2012	*	*	*	*	*	*	*	*	8
Sakaguchi 2009	*	*	*	*	**	*	*	*	9
Santambrogio 2017	*	*	*	*	*	*	*	*	9
Shady 2017	*	*	*	*	**	*	*	*	9
Simo 2011	*	*	*	*	*	*	*	*	8
Thornton 2017	*	*	*	*	**	*	*	*	9
van Tilborg 2016	*	*	*	*	*	*	*	*	8
Vasnani 2016	*	*	*	*	**	*	*	*	9
Vogl 2015	*	*	*	*		*	*	*	7
Xu 2017	*	*	*	*	**	*	*	*	9
Yang 2017	*	*	*	*	*	*	*	*	8
Yin 2009	*	*	*	*	**	*	*	*	9
Zhang 2013	*	*	*	*	**	*	*	*	9

Notes: ^a The NOS scale has eight categories in which stars may be awarded for the study meeting the quality assessment criterion. For the comparability of cohorts on the basis of design or analysis category, up to two stars may be awarded (**); all other categories can be awarded a maximum of one star (*). The maximum number of stars awarded per study is nine and the total stars awarded to each study are summarized in the total column.

Abbreviation: NOS, Newcastle Ottawa Scale.

Data availability

The dataset supporting the conclusions of this article is included in the article (and its supplementary data).