Surgical approach to microwave and radiofrequency liver ablation or hepatocellular carcinoma and colorectal liver metastases less than 5 cm: a systematic review and meta-analysis

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AUTHORS

Moustafa Abdalla¹, Amelia T. Collings², Rebecca Dirks², Edwin Onkendi³, Daniel Nelson⁴, Emily Miraflor⁵, Faique Rahman⁶, Ahmad Ozair⁷, Jake Whiteside², Mihir M Shah⁸, Subhashini Ayloo⁹, Ahmed Abou-Setta¹⁰, Iswanto Sucandy¹¹, Ali Kchaou¹², Samuel Douglas¹³, Patricio Polanco¹⁴, Timothy Vreeland¹⁵, Joseph Buell¹⁶, Mohammed T. Ansari¹⁷, Aurora D. Pryor¹⁸, Bethany J. Slater¹⁹, Ziad Awad²⁰, William Richardson²¹, Adnan Alseidi²², D. Rohan Jeyarajah²³, Eugene Ceppa²

1. Department of Surgery, Harvard Medical School, Boston, MA, USA
2. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
3. Department of Surgery, Texas Tech University Health Sciences, TX, USA
4. Department of Surgery, William Beaumont Army Medical Center, Fort Bliss, TX, USA
5. Department of Surgery, University of California, San Francisco – East Bay, CA, USA
6. Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, India
7. King George’s Medical University, Chowk, Lucknow, India
8. Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA, USA
9. Department of Surgery, Alpert Medical School of Brown University, Providence, RI, USA
10. Knowledge Synthesis, University of Manitoba, Winnipeg, Canada
11. Department of Surgery, University of Central Florida, Tampa, FL, USA
12. Department of Surgery, University of Sfax, Sfax, Tunisia
13. Sentara Medical Group, Norfolk, VA. USA
14. University of Texas Southwestern Medical Center, Dallas, TX, USA
15. Department of Surgery, Brooke Army Medical Center, Houston, TX, USA
16. Department of Surgery and Pediatrics, Tulane University, New Orleans, LA USA
17. School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
18. Department of Surgery, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA
19. Department of Surgery, University of Chicago, IL, USA
20. Department of Surgery, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA
21. Department of Surgery, Ochsner Clinic, New Orleans, LA, USA
22. Department of Surgery, University of California San Francisco, CA, USA
23. Department of Surgery, TCU and UNTHSC School of Medicine, Fort Worth, TX, USA

Address all correspondences to::

Eugene P. Ceppa, MD
Associate Professor of Surgery
Indiana University School of Medicine

ABSTRACT

Background: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the two most common malignant neoplasms of the liver. The objective of this study was to assess outcomes of surgical approaches to liver ablation comparing laparoscopic versus percutaneous microwave ablation (MWA), and MWA versus radiofrequency ablation (RFA) in patients with HCC or CRLM lesions smaller than 5cm.

Methods: A systematic review was conducted across seven databases, including PubMed, Embase and Cochrane, to identify all comparative studies between 1937-2021. Two independent reviewers screened for eligibility, extracted data for selected studies, and assessed study bias using the modified Newcastle Ottawa Scale. Random effects meta-analyses were subsequently performed on all available comparative data.

Results: From 1066 records screened, 11 studies were deemed relevant to the study and warranted inclusion. Eight of the 11 studies were at high or uncertain risk for bias. Our meta-analyses of two studies revealed that laparoscopic MW ablation had significantly higher complication rates compared to a percutaneous approach (risk ratio = 4.66; 95% confidence interval = [1.23, 17.22]), but otherwise similar incomplete ablation rates, local recurrence, and oncologic outcomes. The remaining nine studies demonstrated similar efficacy of MWA and RFA, as measured by incomplete ablation, complication rates, local/regional recurrence, and oncologic outcomes, for both HCC or CRLM lesions less than 5cm (p > 0.05 for all outcomes). There was no statistical subgroup interaction in the analysis of tumors <3cm.

Conclusions: The available comparative evidence regarding both laparoscopic versus percutaneous MWA and MWA versus RFA is limited, evident by the few studies that suffer from high/uncertain risk of bias. Additional high-quality randomized trials or statistically matched cohort studies with sufficient granularity of patient variables, institutional experience, and physician specialty/training will be useful in informing clinical decision making for the ablative treatment of HCC or CRLM.

Key Words: microwave ablation; percutaneous; laparoscopic; radiofrequency ablation; hepatocellular carcinoma; colorectal liver metastases

INTRODUCTION

Hepatectomy remains the gold standard treatment for the two most common malignant neoplasms of the liver, primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM)[1-3]. Unfortunately, when considering both contraindications to surgical treatment (e.g., insufficient future liver remnant, tumor size, number, anatomic distribution) and comorbid conditions that increase surgical morbidity, less than 5-20% of patients are suitable candidates for resection[2-6]. Furthermore, the improvement in long-term prognosis has been modest: the 5-year survival rate is estimated at 20-40%[2, 3]. This is especially concerning given the increasing incidence of primary HCC since the 1990s[7] and the fact that 25-50% of patients with colorectal cancer will develop CRLM[8-10].

The development of (minimally invasive) techniques for tumor ablation by direct application of chemicals or energy have addressed some of these shortcomings, especially for lesions that are less than 5cm [2, 11-14]. With the reduced morbidity and mortality compared to resection, these techniques have expanded the pool of eligible patients, can be used to treat small tumor sizes/multiple tumors, and if clinically indicated, may be repeated to treat recurring tumors[13]. Thermal modalities, including radiofrequency (RFA) and microwave (MWA) ablation, represent the most widely-used ablative techniques. RFA treatment is the most common[12] and an accepted approach in selected patients (e.g., HCC lesions smaller than 3cm) [12, 13, 15]. In contrast, MWA, a more recent addition initially developed for lung cancers[13], has some theoretical benefits over RFA (including less peri-procedural pain, and more predictable ablation)[11-14].

Although both RFA and MWA result in coagulative necrosis via direct application of heat, the physical principles employed are distinct[4, 11-13]. RFA creates a zone of coagulation necrosis through both resistive heating derived from an alternating current driven from the applicator probe (cathode), as well as an accompanying thermal diffusion into adjacent tissues[4, 11]. Comparatively, MWA uses dielectric (electromagnetic) hysteresis which can penetrate tissue that are generally recognized as poor electrical conduits and is generally less reliant on conduction down the thermal gradient (i.e., less indirect application of heat)[11]. MWA can generate more power to produce larger and higher ablation temperatures, but at an increased risk of other complications not as commonly associated with RFA (e.g., thrombosis of the portal vein in cirrhotic patients). Despite our understanding of these physical principles and several systematic reviews on these ablative techniques[2-4, 16], it is unclear how the two modalities and technical variations thereof (laparoscopic, percutaneous, open) compare with respect to procedural-specific morbidity, local/regional recurrence, and survival.

To explore the comparative effectiveness of microwave and radiofrequency ablation, as well as to assess the benefit of percutaneous versus laparoscopic microwave ablation, we conducted a systematic review and meta-analysis to inform our combined Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and Americas Hepato-Pancreato-Biliary Association (AHPBA) guidelines and ultimately help clinicians in selecting ablative treatment modalities for individuals afflicted with primary or secondary liver neoplasms.

METHODS AND MATERIALS

To compare the two aforementioned modalities, the SAGES guidelines committee and representatives from AHPBA formed a working group to perform a systematic review and meta-analysis reported here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines[17]. The subgroup had originally drafted six questions according to the PICO format (Population, Intervention, Comparator, and Outcomes) to guide the literature search (see Appendix 1 – Note 1). However, on completion of the literature search, the working group realized that only sufficient evidence existed to answer two modified questions as follows:

Key Question 1 (KQ1): Should Percutaneous vs. Laparoscopic MW ablation be used for HCC and/or CRLM less than 5cm?

Outcomes: Incomplete Ablation, Local/Regional Recurrence, Complications, Disease Free Survival (DFS), Overall Survival (OS

Key Question 2 (KQ2): Should MW ablation (laparoscopic or open) vs. RF ablation (laparoscopic or open) be used for HCC or CRLM less than 5cm?

Subgroup analysis: HCC or CRLM less than 3cm

Outcomes: Incomplete Ablation, Local/Regional Recurrence, Complications, DFS, OS

Types of interventions

As described above, all studies comparing percutaneous versus laparoscopic MWA of HCC or CRLM were included, as were any comparative studies of surgical approaches to MWA and RFA (including laparoscopic or open) for the same tumors. Studies that included combined chemoembolization and ablation were also included but tagged for possible source of heterogeneity. Any studies that combined resection with ablation were excluded from our meta-analysis.

Types of Outcomes

Five classes of outcomes of interest were specified a priori: (i) incomplete ablation, defined as the number of tumors incompletely ablated out of the total number of tumors (not individual patients); (ii) perioperative complications of Clavien-Dindo grade ≥3; (iii) local/regional recurrence, defined as radiologic and/or histologic identification of recurrent tumor at original site or draining lymph nodes after completed ablation; (iv) disease-free survival; and (v) overall survival.

Literature Search & Eligibility Criteria

A clinically guided search was performed for each of the six key questions (Appendix 1 – Note 1) in December 2019, with the assistance of a medical librarian, across seven databases: the Cochrane library, Clinicaltrials.gov, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, PubMed, the WHO’s International Clinical Trials Registry Platform (ICTRP), and Google Scholar. The full search criteria and the number of records contributed from each database is provided in Appendix 1 – Note 2, including all publications between 1937-2021. All records were combined with EndNote (Clarivate Analytics) then uploaded to Covidence for screening, with duplicates automatically removed in both EndNote and Covidence prior to screening. Exclusion criteria included: reviews that are not systematic reviews and/or meta-analyses, non-English abstracts, non-comparative studies (e.g. case series), and total sample sizes of less than 10 patients across all arms (e.g., case reports or limited case series). An updated search was performed in June 2021 to capture more recent studies or studies not included in the original search.

Study selection

All reviewers participating in the systematic review had received prior training in systematic review methodology. To calibrate reviewers’ ratings for study selection and screening, 100 randomly selected abstracts were reviewed by all reviewers on Abstrackr (Brown University, Providence, Rhode Island). All disagreements were discussed during a conference call. Subsequently, all titles and abstracts were screened by two independent reviewers for relevance and eligibility using Covidence. All irrelevant publications were excluded, as were any remaining duplicates or non-English language studies that bypassed our search filters. Full text review by two independent reviewers was subsequently performed. Exclusion criteria included non-comparative studies, case reports, letters to the editors, abstracts, author replies, and lay press articles Only peer-reviewed English language manuscripts meeting screening criteria were included in our final data extraction. It is also important to note that, while reviews were excluded from the pooled analyses, the reference lists were hand-searched for additional relevant references. Discrepancies were resolved through discussion among the reviewers, with a final decision made by the senior author (E.C.) when necessary.

Risk of bias in individual studies

The modified Newcastle-Ottawa Scale was used to assess risk of bias for observational studies (Appendix 1 – Note 3) [18]. Each study was scored by two independent reviewers. Criteria were assessed for risk of bias across three broad categories: selection, comparability, and outcomes. Our minimum length of follow up to be considered ‘low risk of bias’ from outcomes was a priori defined as 1 year, with length of follow up 3 years or greater as ideal. No randomized control trials were selected for full data extraction, and thus, the Cochrane Risk of Bias Tool was not employed in this systematic review.

Data extraction

Two reviewers independently completed the data extraction forms on Covidence to extract study characteristics, sponsorship source, methods, population (including baseline characteristics), interventions, and a priori determined outcomes. Our primary outcomes, as described above in detail, were incomplete ablation, local/regional recurrence, complication rates, disease-free survival, and overall survival.

Data Synthesis

Study data were synthesized quantitatively. We used RevMan (version 5.4 Nordic Cochrane Centre, Copenhagen, Denmark) for meta-analyses. As all relevant data were dichotomous, we estimated risk ratios (RR) with a Mantel-Haenszel (MH) random effects model. Heterogeneity between studies was assessed using I² and χ² measures. A p < 0.05 was considered significant for χ² values; a I² < 40% was considered low. We meta-analyzed data when heterogeneity across studies was low or remained unexplained.

RESULTS

Across the bibliographic databases and the 33 records identified through hand searching of systematic review reference lists, total 1066 unique records were screened for eligibility with 11 records deemed relevant to the two review questions (PRIMSA flow diagram Figure 1). Each record represented a unique study. All 11 studies were of observational design (see Table 1 and Table 2).

Figure 1. PRISMA flow diagram for the systematic review. The breakdown by question is summarized in Tables 1 and 2.

Table 1. Baseline characteristics of the two studies included to answer KQ1 (percutaneous versus laparoscopic MW ablation). Both studies are retrospective cohort studies from Italian groups that did not have any sponsors listed. No patient from either study underwent embolization. DeCobelli 2017 included both HCC and CRLM, as well as liver metastases from neuroendocrine tumors, pancreatic cancer, lung cancer, and urothelial cancer. DellaCorte 2020 included only HCC patients.

Abbreviations: Microwave ablation, MWA.

Notes:

Criteria

For DeCobelli 2017: Inclusion criteria for primary liver tumors included the presence of a potentially curable liver-confined disease, disease unsuitable to hepatic resection alone due to inadequate functional liver reserve, according to EASL–EORTC guidelines. Inclusion criteria for liver metastases included curative intent of liver-confined disease, contraindication to surgery, and local liver disease control when other treatments such as radiotherapy or chemotherapy were applied to an extrahepatic tumor site. Exclusion criteria were pregnancy, the presence of refractory ascites or coagulopathies not susceptible of medical correction.

For DellaCorte 2020: Inclusion criteria included clinical and imaging evidence of HCC (radiological diagnosis of tumors on pre-operative dynamic contrast-enhanced CT or MRI with a liver-specific acquisition protocol); disease stage 0, A, B deemed amenable of curative treatment (ablation alone or ablation combined with surgery); ablation within one month of last imaging.

Group differences

For DeCobelli 2017:  Even though no comparative analysis was done for the groups of interest (percutaneous ablation vs laparoscopic ablation) to check for any group differences, the authors mention that to verify possible confounding effects, a multivariate constrained mixed effect model of the AZ volume as a function of liver condition and operative approach was fitted. The other independent variables considered in this study (sex, age, proximity to capsule and vessels) showed no evidence of improvement when added to the model.

For DellaCorte 2020: Compared to LMWA, PWMA had more patients who had previous HCC treatment, less patients treated under general anesthesia, more patients with chronic hepatitis C and less with “idiopathic” as the cause of cirrhosis, more patients with BCLC stage A1 and fewer patients with stage A4 or multifocal disease. A higher amount of energy over tumor size was delivered in laparoscopic ablation. All these group differences were statistically significant (p < 0.05).

Table 2. Baseline characteristics of the 9 studies included to answer KQ2 (Surgical MWA vs. Surgical RFA). No sponsors or funding sources were reported for any of the studies.
 Abbreviations (alphabetical order): Colorectal metastases, CRLM; hepatocellular carcinoma, HCC; microwave ablation, MWA; radiofrequency ablation, RFA; standard deviation, SD.

Notes:
* In Lee 2017: Two patients received TACE as treatment for residual disease.

Inclusion and exclusion criteria for each study, as well as a brief discussion of group differences between interventions and tumor locations, is available in Appendix 1 – Note 4.

Key Question 1 (KQ1): Should Percutaneous vs. Laparoscopic MW ablation be used for HCC and/or CRLM less than 5cm?

A total of two observational studies, with 81 and 91 patients who underwent liver-directed microwave thermal ablations, met inclusion criteria for KQ1[19, 20]. Unfortunately, both studies were deemed to have a high risk of bias for all outcomes, driven primarily by poor comparability between intervention groups and inadequately defined follow-up periods (Table 3).

Table 3. Risk of bias for the observational studies included under KQ1 as assessed by a modified Newcastle Ottawa Scale.

Incomplete Ablation: Both studies were included in the meta-analysis for incomplete ablation. Data from 54 laparoscopic and 97 percutaneous MW ablations demonstrated a lower risk of incomplete ablation after the laparoscopic approach, although this was not statistically significant (RR 0.28, 95% CI 0.05-1.55, I² 0%, Figure 2).

Figure 2. Forest plot for incomplete ablation with percutaneous MWA as the reference class

Complications: While neither study was independently significant, meta-analysis revealed an increased MH risk ratio for complications in laparoscopic, versus percutaneous, microwave ablation (risk ratio [RR] = 4.66; 95% confidence interval [CI] = [1.23, 17.22]; Figure 3).

Figure 3. Forest plot for complication rates of laparoscopic versus percutaneous MW ablation

Local/regional recurrence; 1-year disease-free survival; 1-year overall survival: Only one of the two studies merited inclusion in meta-analyses for the three aforementioned outcomes; all were non-significant in comparisons of laparoscopic versus percutaneous MWA (Figure 4). Our limitation to outcomes at 1 year was dictated exclusively by the availability of data (i.e., no outcome data beyond 1 year).

Figure 4a. Forest plot with percutaneous MWA as the reference class for local/regional recurrence.

Figure 4b. Forest plot with percutaneous MWA as the reference class for disease-free survival at 1 year.

Figure 4c. Forest plot with percutaneous MWA as the reference class for overall survival at 1-year.

Key Question 2 (KQ2): Should MW ablation (laparoscopic or open) vs. RF ablation (laparoscopic or open) be used for HCC or CRLM less than 5cm?

Nine comparative studies met inclusion criteria for KQ2 [21-29]. Six of the nine total studies were deemed to have high or uncertain risk of bias (Table 4). The study cohorts ranged from 35 to 391 patients (Table 2).

Table 4. Risk of bias for the observational studies included under KQ2 (MWA vs RFA for lesions smaller than 5cm), as assessed by a modified version of the Newcastle Ottawa Scale.

Incomplete Ablation: Six of nine studies, with data from 348 MWA and 367 RFA, were included in the combined less than 5cm meta-analysis and revealed no difference between MWA and RFA (RR 1.0, 95% CI 0.05-1.55, I² 0%, Figure 5). While the subgroup analysis for tumor less than 3cm favored MWA, it included one study and was not significant (RR 0.19, 95% CI 0.01-3.88, Figure 5).

Figure 5. Forest plot for incomplete ablation with RFA as the reference class.

Complications: Similarly, eight of nine studies, with data from 402 MWA and 480 RFA, were included in the combined less than 5cm meta-analysis and revealed no difference between MWA and RFA (RR 1.0, 95% CI 0.05-1.55, I² 0%, Figure 6). This was consistent for all subgroup analyses, including tumors less than 3cm (RR 0.78, 95% CI 0.72-1.33, I² 0%, Figure 6).

Figure 6. Forest plot for complication rates with RFA as the reference class.

Local/regional recurrence; disease-free survival; overall survival: All comparative meta-analyses between MWA and RFA were non-significant for the three aforementioned outcomes explored in both the cumulative (< 5cm) and sub-group (< 3cm) analyses (Figures 7-9). That is, there were no significant differences between patients who underwent MWA versus RFA with regards to local/regional recurrence (combined MH RR = 0.97, 95% CI 0.73-1.30, I²=0%;  Figure 7). There were also no significant differences for disease-free survival at 1 year (combined MH RR = 0.99, 95% CI = 0.83-1.19, I²=15%), 3 years (RR = 1.03, 95% CI = 0.73-1.45, I²=0%), and 5 years (RR = 1.09, 95% CI = 0.79-1.51, I²=0%; Figure 8). Similarly, we observed no significant differences in the metanalyses for overall survival at 1 year (RR = 0.99, 95% CI = 0.97-1.01, I²=7%), 3 years (RR = 0.99, 95% CI = 0.94-1.05, I²=0%), and 5 years (RR = 1.01, 95% CI = 0.91-1.11, I²=0%; Figure 9).

Figure 7. Forest plot for local/regional recurrence with RFA as the reference class.

Figure 8a. Forest plot for DFS with RFA as the reference class at 1 year.

Figure 8b. Forest plot for DFS with RFA as the reference class at 3 years.

Figure 8c. Forest plot for DFS with RFA as the reference class at 5 years.

Figure 9a. Forest plot for OS with RFA as the reference class a 1 year.

Figure 9b. Forest plot for OS with RFA as the reference class at 3 years.

Figure 9c. Forest plot for OS with RFA as the reference class at 5 years.

DISCUSSION

The purpose of this systematic review was to review the literature and pool appropriate comparative data to better inform clinical decision making regarding both the ablative modality and technical approach for the treatment of the two most common malignant liver neoplasms. Despite a comprehensive literature search, we identified less than a dozen relevant studies with the majority at high or uncertain risk of bias. Within these constraints, we noted that the efficacy of MWA, as measured by incomplete ablation, complication rates, local/regional recurrence, and survival, appears similar to that of RFA both for HCC and CRLM lesions less than 5cm. This was consistent in the subgroup analysis of lesions less than 3cm. With regards to approach, laparoscopic MWA had significantly higher complication rates, but otherwise similar risk of incomplete ablation, local/regional recurrence, and survival.

Relationship to literature. There have been several comparative studies [30, 31, 32] and systematic reviews [33-35] that have attempted to address outcomes (including local disease control and survival) of percutaneous MWA versus RFA for HCC and CRLM. While most of these studies hint at similar completion frequencies, complication rates, and survival between MWA and RFA, they disagree with regards to local tumor control and progression[33, 34]. This controversy, in part, stems from substantial variation in the clinical contexts in which these ablation technologies were deployed (e.g., tumor size, number, anatomic distribution, as well as patient profiles/comorbidities), making it difficult to compare or to perform a meta-analysis of the results. Further, none of these studies have explored other surgical approaches (e.g., laparoscopic, or open).  Our analyses here suggest that laparoscopic or open MWA and RFA are similarly safe and effective for lesions smaller than 5cm. However, given the limited evidence and quality, these results are not definitive. In contrast, very few studies have compared percutaneous and laparoscopic MWA of malignant liver neoplasms[19, 20]. Thus, while this limits the power of our meta-analysis, our systematic review provides a comprehensive look at the existing literature. Our results suggest that percutaneous MWA is safer than laparoscopic MWA, with regards to complication rates, but no difference in ablative completeness rates or survival. Although given the major differences in patients included in each cohort (including more multifocal disease patients in the laparoscopic group, as well as overall sicker patients with higher incidence of chronic hepatitis C), it is unclear how confounded these observations are.

Limitations. All 11 comparative studies included in our analyses were observational (all but one being retrospective cohort studies), with relatively small sample sizes and short follow-up. Furthermore, the majority (two out of two of the percutaneous versus laparoscopic MWA studies, and five of nine of the MWA vs RFA studies) were deemed at either uncertain or high risk of bias. No randomized clinical trials met our inclusion criteria. Altogether, the paucity of high-quality evidence limits the definitive with which we can present these conclusions. Restrictions in our literature search (e.g., to English language only studies) are likely to have had minimal impact, given both the national/geographic diversity of the included studies (China, Egypt, Italy, Japan, and USA) and that only two full text articles were excluded (Figure 1).

Relevance to clinical practice. Our findings suggest MWA and RFA for HCC or CRLM lesions less than 5cm are comparable with respect to efficacy and safety. Further, our results also support that percutaneous MWA should be preferred to laparoscopic approaches due to lower complication rates. However, as discussed above, given the limited evidence and quality of data, these results do not definitively eliminate the clinical equipoise surrounding our PICO questions.

Future research recommendations. Given the paucity of comparative observational studies and the complete absence of randomized control trials, there is a pressing need for higher-quality evidence to inform both selection of the ablative technology and technical approach. This evidence must have adequately sufficient follow-up and must clearly define the clinical contexts/indications (if any) in which one approach or technique may be preferred over another (e.g., tumor size or anatomic distribution). We encourage researchers to ensure sufficient granularity in the data (e.g., molecular biology, location, experience of institution, and physician specialty [e.g., interventional radiology vs surgery]) to help discriminate between institutional and intervention effects, as well as identify appropriate patients for each intervention.

CONCLUSION

Available evidence indicates that there was no difference between MWA and RFA treatment with a surgical (laparoscopic or open) approach for HCC or CRLM lesions less than 5cm, with respect to safety or efficacy. Further, percutaneous MWA is preferable to laparoscopic approaches due to lower complication rates but is otherwise comparable with respect to completeness rates and survival. Our systematic review also revealed a definitive need for high quality comparative/population-based studies to better guide clinical decision making. While the evidence is limited and of variable quality, the results described here will form the basis of an upcoming integrated SAGES-AHPBA clinical practice guideline.

APPENDIX

Liver Ablation Systematic Review Appendix 1

REFERENCES

1. Abdalla EK, Vauthey J-N, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA (2004) Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 239:818-825; discussion 825-827
2. Bhardwaj N, Strickland A, Ahmad F, Dennison A, Lloyd D (2010) Liver ablation techniques: a review. Surg Endosc 24:254-265
3. McGhana JP, Dodd III GD (2001) Radiofrequency ablation of the liver: current status. AJR Am J Roentgenol. 176:3-16
4. Decadt B, Siriwardena AK (2004) Radiofrequency ablation of liver tumours: systematic review. Lancet Oncol 5:550-560
5. European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 56:908-943
6. Benson AB 3rd, Abrams TA, Ben-Josef E, Bloomston PM, Botha JF, Clary BM, Covey A, Curley SA, D’Angelica MI, Davila R Ensminger WD, Gibbs JF, Laheru D, Malafa MP, Marrero J, Meranze SG, Mulvihill SJ, Park JO, Posey JA, Sachdev J, Salem R, Sigurdson ER, Sofocleous C, Vauthey JN, Venook AP, Goff LW, Yen Y, Zhu AX (2009) NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 7:350-391
7. Rich NE, Yopp AC, Singal AG, Murphy CC (2020) Hepatocellular carcinoma incidence is decreasing among younger adults in the United States. Clin Gastroenterol Hepatol 18:242-248e5
8. Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, Jemal A (2017) Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Inst 109: djw322
9. International Agency for Research on Cancer (2012) GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012. [Database] https://gco.iarc.fr/
10. Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow H, Duckworth A, Heis Mahvi blative Therapies for Hepatic Neoplasmster P, Praseedom R, Jah A (2020) Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 11:761-808
11. Wells SA, Hinshaw JL, Lubner MG, Ziemlewicz TJ, Brace CL, Lee FT (2015) Liver ablation: best practice. Radiol Clin North Am 53:933-971
12. Izzo F, Granata V, Grassi R, Fusco R, Palaia R, Delrio P, Carrafiello G, Azoulay D, Petrillo A, Curley SA (2019) Radiofrequency ablation and microwave ablation in liver tumors: an update. Oncologist 24:e990-e1005
13. Mahvi DA, Mahvi DM (2019) Ablative Therapies for Hepatic Neoplasms. In: Yeo (ed) Shackelford’s Surgery of the Alimentary Tract, 2 Volume Set, 8^th ed, Chapter 126, Elsevier; 1481-1487
14. Poulou LS, Botsa E, Thanou I, Ziakas PD, Thanos L (2015) Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Hepatol 7:1054-1063
15. Violi NV, Duran R, Guiu B, Cercueil J-P, Aubé C, Digklia A, Pache I, Deltenre P, Knebel J-F, Denys A (2018) Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol Hepatol 3:317-325
16. Sutherland LM, Williams JA, Padbury RT, Gotley DC, Stokes B, Maddern GJ (2006) Radiofrequency ablation of liver tumors: a systematic review. Arch Surg 141:181-190
17. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, McKenzie JE (2021) PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 372:n160
18. Peterson J, Welch V, Losos M, Tugwell P (2011) The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute 2:1-12
19. Della Corte A, Ratti F, Monfardini L, Marra P, Gusmini S, Salvioni M, Venturini M, Cipriani F, Aldrighetti L, De Cobelli F (2020) Comparison between percutaneous and laparoscopic microwave ablation of hepatocellular carcinoma. Int J Hyperthermia 37:542-548
20. De Cobelli F, Marra P, Ratti F, Ambrosi A, Colombo M, Damascelli A, Sallemi C, Gusmini S, Salvioni M, Diana P , Cipriani F, Venturini M, Aldrighetti L, Del Maschio A (2017) Microwave ablation of liver malignancies: comparison of effects and early outcomes of percutaneous and intraoperative approaches with different liver conditions. Med Oncol 34:49
21. An C, Li W-Z, Huang Z-M, Yu X-L, Han Y-Z, Liu F-Y, Wu S-S, Yu J, Liang P, Huang J (2021) Small single perivascular hepatocellular carcinoma: comparisons of radiofrequency ablation and microwave ablation by using propensity score analysis. Eur Radiol 31:4764-4773
22. Correa-Gallego C, Fong Y, Gonen M, D’Angelica MI, Allen PJ, DeMatteo RP, Jarnagin WR, Kingham TP (2014) A retrospective comparison of microwave ablation vs. radiofrequency ablation for colorectal cancer hepatic metastases. Ann Surg Oncol 21:4278-4283
23. Lee K-f, Wong J, Hui JW-y, Cheung Y-s, Chong CC-n, Fong AK-w, Yu SC-h, Bo-san Lai P (2017) Long-term outcomes of microwave versus radiofrequency ablation for hepatocellular carcinoma by surgical approach: a retrospective comparative study. Asian J Surg 40:301-308
24. Sakaguchi H, Seki S, Tsuji K, Teramoto K, Suzuki M, Kioka K, Isoda N, Ido K, Research JSfLT (2009) Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi‐center study. Hepatol Res 39:47-52
25. Takahashi H, Kahramangil B, Kose E, Berber E (2018) A comparison of microwave thermosphere versus radiofrequency thermal ablation in the treatment of colorectal liver metastases. HPB (Oxford) 20:1157-1162
26. Yang B, Li Y (2017) A comparative study of laparoscopic microwave ablation with laparoscopic radiofrequency ablation for colorectal liver metastasis. J BUON 22:667-672
27. Simo KA, Sereika SE, Newton KN, Gerber DA (2011) Laparoscopic‐assisted microwave ablation for hepatocellular carcinoma: Safety and efficacy in comparison with radiofrequency ablation. J Surg Oncol 104:822-829
28. Santambrogio R, Chiang J, Barabino M, Meloni FM, Bertolini E, Melchiorre F, Opocher E (2017) Comparison of laparoscopic microwave to radiofrequency ablation of small hepatocellular carcinoma (≤ 3cm). Ann Surg Oncol 24:257-263
29. Iida H, Aihara T, Ikuta S, Yamanaka N (2012) A comparative study of therapeutic effect between laparoscopic microwave coagulation and laparoscopic radiofrequency ablation. Hepatogastroenterology 60:662-665
30. Potretzke TA, Ziemlewicz TJ, Hinshaw JL, Lubner MG, Wells SA, Brace CL, Agarwal P, Lee FT Jr (2016) Microwave versus radiofrequency ablation treatment for hepatocellular carcinoma: a comparison of efficacy at a single center. J Vasc Interv Radiol 27:631-638
31. Xu Y, Shen Q, Wang N, Wu P-P, Huang B, Kuang M, Qian G-J (2017) Microwave ablation is as effective as radiofrequency ablation for very-early-stage hepatocellular carcinoma. Chin J Cancer 36:14
32. Liu W, Zheng Y, He W,Zou R, Qiu J, Shen J, Yang Z, Zhang Y, Wang C, Wang Y, Zuo D, Li B, Yuan Y (2018) Microwave vs radiofrequency ablation for hepatocellular carcinoma within the Milan criteria: a propensity score analysis. Aliment Pharmacol Ther 48:671-681
33. Glassberg MB, Ghosh S, Clymer JW, Qadeer RA, Ferko NC, Sadeghirad B, Wright GW, Amaral JF (2019) Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: a systematic review and meta-analysis. Onco Targets Ther 12:6407-6438
34. Facciorusso A, Di Maso M, Muscatiello N (2016) Microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis. Int J Hyperthermia 32:339-344
35. Tan W, Deng Q, Lin S, Wang Y, Xu G (2019) Comparison of microwave ablation and radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis. Int J Hyperthermia 36:263-271