Quality assessment

RCTs

Risk of bias assessments and individual study quality assessments are presented in Table S2 and Figure S1 (see original article). Overall, the quality of studies was acceptable, with most studies having low or unclear risk of bias across most domains. Two studies reported the methods for random sequence generation (ie, coin flip and computer-generated)40,41 and the other two studies20,21 were assigned an unclear risk of selection bias as no information was provided. The methods for allocation concealment were defined by one study (centralized computer-generated allocation list)41 and the other three studies20,21,40 were assigned an unclear risk of selection bias. The risk of bias associated with blinding of patients or outcome assessors was considered to be low for outcomes because of their objectivity. For three studies, patient withdrawals, loss to follow-up, and missing data were minimal. However, one study reported a loss to follow-up of greater than 20% and was assigned high risk for attrition bias due to incomplete OS data.40 The bias associated with selective reporting was unclear for all studies.


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Observational studies

The NOS scores for observational studies are presented in Table S3. The 24 observational studies were given scores that ranged from 7 to 9; the studies varied in terms of comparability and adequacy of follow-up. All studies were either truly or somewhat representative of the exposed cohort, drew the non exposed cohort from the same community as the exposed cohort, and used secure records for exposure ascertainment. Most studies received two stars for comparability; however, seven studies received one star as they did not report Child–Pugh classification,24,51 or reported differences in patient age, sex, ablation approach, tumor size, or primary origin between treatment arms. These variables were either not controlled for, or adjusted analyses showed that one or more of them affected outcomes.23,25,28,47,53 Only one study received no stars for comparability because it did not report Child–Pugh classification and reported significant differences between treatment arms for patient age and tumor size.32 Additionally, one study did not receive a star for the adequacy of the follow-up period as it did not report the follow-up time for the RFA group.47 There were no studies that had a loss to follow-up that could potentially impact results (ie, >20%).

Analysis

LTP

For the outcome of LTP, three RCTs and 15 observational studies were included. The meta-analysis demonstrated that the risk of LTP was significantly reduced by 30% with MWA compared with RFA (RR=0.70; P=0.02) (Table 2, Figure 2). For the three RCTs only, LTP was significantly reduced by 45% with MWA (RR=0.55; P=0.007). Meta-regression indicated that average study follow-up duration did not impact LTP outcomes (P=0.78). A sensitivity analysis excluding studies that reported “recurrence,” but did not specify “local recurrence”21,32 was also performed; results remained consistent with the main analysis (RR=0.69, 95% CI 0.51–0.94, P=0.02).

Technique efficacy measured at one week to three months post ablation was reported by four RCTs and 14 observational studies. One RCT reported technique efficacy at one week40 and three studies did not specify the time point at which technique efficacy was assessed.20,26,51 The meta-analysis demonstrated that technique efficacy was not significantly different between MWA and RFA (RR=1.01; P=0.25). For the four RCTs only, there were also no significant differences (RR=1.01; P=0.23) (Table 2, Figure 4, Figure S2). A sensitivity analysis excluding studies that reported technique efficacy at one-week40 or an unspecified time point20,26,51 was also performed; results remained consistent with the main analyses (RR=1.02, 95% CI 0.99–1.05; P=0.20).

Based on sample size, weighted averages demonstrated that OS at three years (77% versus 73%) and five years (63% versus 59%) was higher with MWA compared with RFA, respectively (Figure 3), although the meta-analyses indicated no significant differences [one-year OS (RR=1.00; P=0.80), three-year OS (RR=1.03; P=0.40), and five-year OS (RR=1.03; P=0.60)]. For the two RCTs only, one-year OS was not significantly different between MWA and RFA (RR=1.17; P=0.43) (Table 2, Figure 4, Figure S3–S5).


Similar to OS, weighted averages showed that DFS at one year (83% versus 81%), three years (57% versus 51%), and five years (39% versus 34%) was higher with MWA as compared with RFA (Figure 3); however, the meta-analysis indicated these differences were not statistically significant [one-year (RR=1.00; P=0.93), three-year (RR=1.05; P=0.27), and five-year (RR=0.97; P=0.86) DFS] (Table 2, Figure 4, Figure S6–S8).

Although not statistically significant, the results of the meta-analysis for EHM favored MWA compared with RFA, that is, the incidence of EHM was 34% lower with MWA compared with RFA (RR=0.66; P=0.06). Similarly, for the outcome of IDL, MWA risk was non significantly lower compared with RFA (RR=0.93; P=0.40). When only pooling RCTs, IDL was significantly reduced by 15% with MWA vs RFA (RR=0.85, P=0.03) (Table 2, Figure 4, Figure S9–S10).

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