Abstract: We identified three randomised trials with 261 participants for inclusion. The risk of bias was low in one and high in two trials. Two of the randomised trials compared PEI versus PAI; we included 185 participants in the analysis. The overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not statistically significantly different between the intervention groups of the two trials. Trial sequential analysis for the comparison PEI versus PAI including two trials revealed that the number of participants that were included in the trials were insufficient in order to judge a relative risk reduction of 20%. Data on the duration of hospital stay were available from one trial for the comparison PEI versus PAI showing a significantly shorter hospital stay for the participants treated with PEI (mean 1.7 days; range 2 to 3 days) versus PAI (mean 2.2 days; range 2 to 5 days). Quality of life was not reported. There were only mild adverse events in participants treated with either PEI or PAI such as transient fever, flushing, and local pain. One randomised trial compared PEI versus surgery; we included 76 participants in the analyses. There was no significant difference in the overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group while three postoperative deaths occurred in the surgery group. In addition to the three randomised trials, we identified one quasi-randomised study comparing PEI versus PAI. Due to methodological flaws of the study, we extracted only the data on adverse events and presented them in a narrative way. We found no randomised trials that compared PEI or PAI versus no intervention, best supportive care, sham intervention, or other percutaneous local ablative therapies excluding RFTA. We found also no randomised clinical trials that compared PAI versus other interventional treatments or surgery. We identified two ongoing randomised clinical trials. One of these two trials compares PEI versus surgery and the other PEI versus transarterial chemoembolization. To date, it is unclear whether the trials will be eligible for inclusion in this meta-analysis as the data are not yet available. This review will not be updated until new randomised clinical trials are published and can be used for analysis. PEI versus PAI did not differ significantly regarding benefits and harms in people with early HCC, but the two included trials had only a limited number of participants and one trial was judged a high risk of bias. Thus, the current evidence precludes us from making any firm conclusions. There was also insufficient evidence to determine whether PEI versus surgery (segmental liver resection) was more effective, because conclusions were based on a single randomised trial. While some data from this single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make a reliable assessment impossible. We found no trials assessing PEI or PAI versus no intervention, best supportive care, or sham intervention. There is a need for more randomised clinical trials assessing interventions for people with early stage HCC. Such trials should be conducted with low risks of systematic errors and random errors.

Plain-language summary: The review authors searched the medical literature in order to clarify the role of PEI and PAI for the treatment of liver cancer and to compare their benefits and harms with no treatment, with placebo (a pretend treatment), or with other treatments (such as laser, cryoablation, or microwave ablation; hepatic resection; and liver transplantation). We collected and analysed data from randomised clinical trials (where people were allocated at random to one of two or more treatments groups) of people with liver cancer who were able to receive PEI or PAI. Evidence is current to July 2014. The review authors only identified three randomised trials with 261 participants. The risk of bias was low in one and high in two trials. We found two trials that compared PEI versus PAI and one trial that compared PEI versus surgery. We found no trials that compared PEI or PAI versus sham (pretend) intervention, best supportive care, cryotherapy, laser-induced thermotherapy, or high-frequency ultrasound. We found no randomised trials that compared PAI versus surgery. The review authors found low-quality evidence suggesting that PEI yielded the same result as PAI regarding overall survival (the length of time that the person remains alive) and recurrence-free survival (time that the person remains free of cancer). We calculated the number of participants that would be required to judge a relative risk reduction (relative risk is a comparison of the risk of an event happening for one treatment group compared with another treatment group) for survival of 20%. We found that for the comparisons PEI versus PAI, the number of participants was too low to reach valid conclusions. In both groups, participants reported the occurrence of mild side effects such as transient fever, flushing, and local pain. Based on one randomised trial with high risk of bias, there was very low quality evidence that surgical resection does not seem to be superior to PEI in people with early liver cancer. Of note, no severe side effects occurred in people treated with PEI while there were three postoperative deaths in people treated surgically. Again, too few participants were randomised to claim or reject important differences. There is a need for more randomised clinical trials assessing interventions for people with early-stage liver cancer. Such trials should be conducted with low risks of bias (systematic errors, that is overestimation of benefits and underestimation of harms) and of play of chance (random errors, that is errors due to too few participants and too few outcomes).