Key messages
– We do not know whether microwave coagulation, added to another method of destroying cancer cells given directly to the liver (conventional transarterial chemoembolisation (TACE)), as compared with TACE alone, has benefit in terms of side effects or complications.
– We do not know whether microwave coagulation compared with conventional surgery or another method of destroying cancer cells (radiofrequency ablation) has benefit in terms of death, longer life, and side effects or complications.
What are liver metastases and microwave coagulation?
Liver metastases are new cancer sites that spread to other parts of the body. They commonly originate from cancers of the lung, stomach, colon (large intestine), rectum, and endometrium (lining of the womb). There are different ways to treat liver metastases in people in whom resection (surgical removal of the cancer) for cure is not feasible. One method, microwave ablation, requires placing a special electrode near the cancer site, which destroys surrounding cancer cells using electromagnetic waves.
What did we want to find out?
We wanted to find out if microwave ablation provides benefit over no intervention, other methods of destroying cancer cells given directly to the liver, or other types of treatments working throughout the whole body, when applied to people with liver metastases, regardless of the location of the primary cancer. We looked at the likelihood of death, how long people lived, whether it was possible to eliminate metastases, how often tumours returned, whether disease worsened, the quality of life in terms of health changes, and whether any side effects occurred.
What did we do?
We searched medical databases for randomised trials comparing microwave ablation with no intervention or other types of treatment of liver metastases. In a randomised trial, participants are allocated at random to the study treatments.
What did we find?
We found three trials, all conducted in upper-middle and high-income countries.
One study in China allocated 50 people to microwave ablation plus conventional TACE versus conventional TACE alone. In conventional TACE, a mixture of a drug toxic for cancer cells and a substance blocking blood vessels is injected directly to the artery feeding the tumour to destroy and close it. The study was very uncertain about the effect of microwave ablation plus conventional TACE on decreasing the size of the tumour. It reported side effects in the microwave ablation group only, such as fever, mild stomach pain, signs of mild liver inflammation or damaged, and mild fluid accumulation in the abdomen. Authors did not report how many people died, whether quality of life improved after treatment, whether people lived longer, whether metastases were eliminated, and whether cancer returned.
One study in Japan allocated 40 people to microwave ablation versus conventional surgery. The trial reported that the proportion of people surviving three years later was similar in both groups. People lived for similar periods of time (about 27 months with microwave ablation and 25 months with conventional surgery). The frequency of side effects or complications was similar between treatments, but people in the conventional surgery group more frequently required blood transfusion. The trial did not provide data on quality of life, whether metastases were eliminated, and whether cancer returned.
One study in Germany allocated 50 people to microwave ablation versus another method of destroying cancer cells (using radiofrequency waves called radiofrequency ablation). The study reported that the proportion of people dying was similar in both groups. Comparable numbers of people in both groups lived for one, two, and three years. There were two minor complications in the radiofrequency ablation group. In the microwave ablation group, cancer did not return to the same area after 12 months in any participants. However, in the radiofrequency ablation group, cancer returned to the same area in two people. Cancer appeared in a different area of the body in 10 people in the microwave ablation group and nine people in the radiofrequency ablation group. The trial did not report on quality of life, time to death, and whether metastases were eliminated.
Further randomised clinical trials are needed to strengthen the evidence on the effect of microwave ablation compared with treatments described above. We found no evidence for the comparison of microwave ablation with other methods of destroying cancer cells and treatments working throughout the whole body.
What are the limitations of the evidence?
Our confidence in the results is limited because none of the trials clearly reported their methods, or whether trial participants knew the treatment received. We still lack evidence on the effect of microwave ablation in addition to conventional TACE as compared with conventional TACE alone on death, quality of life, living longer, eliminating metastases, cancer returning, as well as on the effect of microwave ablation compared to conventional surgery and radiofrequency ablation on quality of life, eliminating metastases, and cancer returning.
How up to date is this evidence?
The evidence is up to date to 14 April 2023.
The evidence is very uncertain about the effect of microwave ablation in addition to conventional TACE compared with conventional TACE alone on adverse events or complications. We do not know if microwave ablation compared with conventional surgery may have little to no effect on all-cause mortality. We do not know the effect of microwave ablation compared with radiofrequency ablation on all-cause mortality and adverse events or complications either.
Data on all-cause mortality and time to mortality, HRQoL, adverse events or complications, cancer mortality, disease-free survival, failure to clear liver metastases, recurrence of liver metastases, time to progression of liver metastases, and tumour response measures were either insufficient or were lacking.
In light of the current inconclusive evidence and the substantial gaps in data, the pursuit of additional good-quality, large randomised clinical trials is not only justified but also essential to elucidate the efficacy and comparative benefits of microwave ablation in relation to various interventions for liver metastases.
The current version of the review, in comparison to the previous one, incorporates two new trials in two additional microwave ablation comparisons: 1. in addition to conventional TACE versus conventional TACE alone and 2. versus radiofrequency ablation.
Liver metastases (i.e. secondary hepatic malignancies) are significantly more common than primary liver cancer. Long-term survival after radical surgical treatment is approximately 50%. For people in whom resection for cure is not feasible, other treatments must be considered. One treatment option is microwave coagulation utilising electromagnetic waves. It involves placing an electrode into a lesion under ultrasound or computed tomography guidance.
To evaluate the beneficial and harmful effects of microwave coagulation versus no intervention, other ablation methods, or systemic treatments in people with liver metastases regardless of the location of the primary tumour.
We used standard, extensive Cochrane search methods. The latest date of search was 14 April 2023.
Randomised clinical trials assessing beneficial or harmful effects of microwave coagulation and its comparators in people with liver metastases, irrespective of the location of the primary tumour. We included trials no matter the outcomes reported.
We followed standard Cochrane methodological procedures. Our primary outcomes were: all-cause mortality at the last follow-up and time to mortality; health-related quality of life (HRQoL); and any adverse events or complications. Our secondary outcomes were: cancer mortality; disease-free survival; failure to clear liver metastases; recurrence of liver metastases; time to progression of liver metastases; and tumour response measures. We used risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) to present the results. Two review authors independently extracted data and assessed the risk of bias using the Cochrane RoB 1 tool. We used GRADE methodology to assess the certainty of the evidence.
Three randomised clinical trials fulfilled the inclusion criteria. The control interventions differed in the three trials; therefore, meta-analyses were not possible. The trials were at high risk of bias. The certainty of evidence of the assessed outcomes in the three comparisons was very low. Data on our prespecified outcomes were either missing or not reported.
Microwave coagulation plus conventional transarterial chemoembolisation (TACE) versus conventional TACE alone
One trial, conducted in China, randomised 50 participants (mean age 60 years, 76% males) with liver metastases from various primary sites. Authors reported that the follow-up period was at least one month. The trial reported adverse events or complications in the experimental group only and for tumour response measures. There were no dropouts in the trial. The trial did not report on any other outcomes.
Microwave ablation versus conventional surgery
One trial, conducted in Japan, randomised 40 participants (mean age 61 years, 53% males) with multiple liver metastases of colorectal cancer. Ten participants were excluded after randomisation (six from the experimental and four from the control group); thus, the trial analyses included 30 participants. Follow-up was three years. The reported number of deaths from all causes was 9/14 included participants in the microwave group versus 12/16 included participants in the conventional surgery group. The mean overall survival was 27 months in the microwave ablation and 25 months in the conventional surgery group. The three-year overall survival was 14% with microwave ablation and 23% with conventional surgery, resulting in an HR of 0.91 (95% CI 0.39 to 2.15). The reported frequency of adverse events or complications was comparable between the two groups, except for the required blood transfusion, which was more common in the conventional surgery group. There was no intervention-related mortality. Disease-free survival was 11.3 months in the microwave ablationgroup and 13.3 months in the conventional surgery group. The trial did not report on HRQoL.
Microwave ablation versus radiofrequency ablation
One trial, conducted in Germany, randomised 50 participants (mean age 62.8 years, 46% males) who were followed for 24 months. Two-year mortality showed an RR of 0.62 (95% CI 0.26 to 1.47). The trial reported that, by two years, 76.9% of participants in the microwave ablationgroup and 62.5% of participants in the radiofrequency ablation group survived (HR 0.63, 95% CI 0.23 to 1.73). The trial reported no deaths or major complications during the procedures in either group. There were two minor complications only in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial reported technical efficacy in 100% of procedures in both groups. Distant recurrence was reported for 10 participants in the microwave ablation group and nine participants in the radiofrequency ablation group (RR 1.03, 95% CI 0.50 to 2.08). No participant in the microwave ablation group demonstrated local progression at 12 months, while that occurred in two participants in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial did not report on HRQoL.
One trial reported partial support by Medicor (MMS Medicor Medical Supplies GmbH, Kerpen, Germany) for statistical analysis. The remaining two trials did not provide information on funding.
We identified four ongoing trials.