Microwave Ablation Compared With radiofrequency Ablation for Treatment of Hepatocellular Carcinoma and Liver Metastases: A Systematic Review and Meta-analysis

Purpose: Percutaneous ablation techniques, including microwave ablation (MWA) and radiofrequency ablation (RFA), have become important minimally invasive treatment options for liver cancer. This systematic review compared MWA with RFA for treatment of liver cancer.
Methods: The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was conducted for randomized and observational studies published from 2006 onwards. A random-effects model was used for meta-analyses and local tumor progression (LTP), technique efficacy, overall survival (OS), disease-free survival (DFS), intrahepatic de novo lesions (IDL), extrahepatic metastases (EHM), length of stay (LOS), and complications were analyzed. Subgroup and sensitivity analyses were also conducted.
Results: Of 1379 studies identified, 28 randomized and observational studies met inclusion criteria. The main analysis demonstrated that LTP was significantly reduced by 30% with MWA versus RFA (RR=0.70; P=0.02) (all studies) and by 45% with MWA versus RFA (RR=0.55; P=0.007) (randomized studies only). There were no significant differences between MWA and RFA for other efficacy and safety outcomes. Higher frequency (2450 MHz) and larger tumor size (≥2.5 cm) are amongst variables that may be associated with improved outcomes for MWA. Sensitivity analyses were generally congruent with the main results.
Conclusion: MWA is at least as safe and effective as RFA for treating liver cancer and demonstrated significantly reduced LTP rates. Future studies should assess time and costs associated with these two treatment modalities.
Keywords: microwave ablation, radiofrequency ablation, hepatocellular carcinoma, meta-analysis, liver cancer

INTRODUCTION

Primary liver cancer is the second leading cause of cancer-related deaths and accounted for 788,000 mortalities in 2015.¹ Surgical resection is considered the gold standard of treatment for curative intent but is often only possible in the early stages of hepatocellular carcinoma (HCC) and among those with limited cirrhosis.² During the past ten years, percutaneous ablation has become an important minimally invasive alternative to surgery for liver cancer.³

Radiofrequency ablation (RFA) is currently the most widely used thermal ablation modality for unresectable, early-stage, hepatic malignancy.² Microwave ablation (MWA), which was first introduced in 1994,⁴ has recently increased in use as a result of several significant advancements in the technology and improvements in the clinical application. These advancements include improvements in microwave applicator tissue attachment, spatially and synchronously distributed power to multiple antennas,^5,6 and the development of internally cooled applicators with distal energy control.^7–9

The primary clinical advantages these advancements in MWA have provided are higher temperatures and faster heating than RFA, shorter ablation times, larger ablation volumes, and less heat sink effect.⁸ Although MWA and RFA both destroy tissue via thermally induced coagulative necrosis and the frequencies of microwaves used in MWA are from the radiofrequency spectrum,¹⁰ the two ablative modalities differ in their mechanisms of energy deposition.¹¹ RFA has limited effectiveness in tissues with low electrical conductivity (eg adipose tissue)⁸ since it requires an electrically conductive route through which to transfer resistive heat. RFA applies frequencies from 450 to 500 kHz to destroy tissues in the proximity of the electrode by causing friction that results in heating. The heating produced by RFA is maintained from 50°C to 100°C to avoid charring the tissue and rendering it electrically non conductive.^8,11 Charred tissue acts as an insulator that prevents radiofrequency energy transfer to surrounding tissue, thus limiting ablation volumes. The optimal protocols for maximizing RFA ablation volumes involve using slow and methodical energy deposition. In contrast, MWA applies an electromagnetic field of either 915 or 2450 MHz to the tissue surrounding the antenna, heating it to >150°C via dielectric polarization¹¹ and is most effective in tissues with high water content.⁸ The MWA direct heating mechanism leads to larger, more homogenous ablation zones than RFA, that are created more quickly.^8,12 MWA is less susceptible to the heat sink effect^11,13,14 which is the dissipation of heat via blood vessel perfusion.^11,12 Reduced heat sink effect susceptibility may enable MWA to produce larger ablation zones. Larger and more uniform ablation zones with MWA may destroy neoplastic cells more effectively compared with RFA, potentially impacting local tumor progression (LTP).

Meta-analyses have compared MWA with RFA for the treatment of HCC.^15–18 Generally, these studies have shown similar efficacy and safety between these modalities, with some benefit in LTP for MWA in larger hepatic tumors.^17,18 However, several clinical studies, not included within these meta-analyses, have been published recently.^19–29 Moreover, these meta-analyses have been limited by the type and number of outcomes included. The aim of this meta-analysis is to compare the efficacy and safety of MWA to RFA for the treatment of patients with HCC or liver metastasis. The meta-analysis included both randomized and observational studies; the outcomes were the rate of LTP, technique efficacy, overall survival (OS), disease-free survival (DFS), intrahepatic de novo lesions (IDL), extrahepatic metastasis (EHM), length of stay (LOS), and complications.

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