The Long-Term Efficacy of Radiofrequency Ablation Versus Laparoscopic Hepatectomy for Small Hepatocellular Carcinoma in East Asia: A Systematic Review and Meta-Analysis


Radiofrequency Ablation
Minimally Invasive Surgery
Laparoscopic Hepatectomy
Hepatocellular Carcinomas

How to Cite

Lu , X., Li , Z. ., Liu , Y. ., Wang , Z. ., Peng , F. ., Yu, Q. ., Fu, X. . ., & Ji, B. . (2020). The Long-Term Efficacy of Radiofrequency Ablation Versus Laparoscopic Hepatectomy for Small Hepatocellular Carcinoma in East Asia: A Systematic Review and Meta-Analysis. Iranian Red Crescent Medical Journal, 22(7). Retrieved from


Context: Hepatocellular carcinoma (HCC) is a common malignant cancer and the second leading cause of cancer-related deaths around the world. Radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) have been adopted for the treatment of HCC. The aim of the meta-analysis was to explore the long-term efficacy of RFA compared with LH for small HCC (sHCC) patients in the East Asian population.

Evidence Acquisition: We performed a systematic review and meta-analysis by the literature search on PubMed, Cochrane Library, EMBASE, Chinese Biological Medical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang from their inception until October 10, 2019, for comparing the long-term efficacy outcomes of RFA with LH.

Results: Fourteen retrospective studies with 1,390 subjects were included in the meta-analysis. Compared with the LH-treated group, RFA could raise the local recurrence rate under median follow-up duration and reduce disease-free survival (DFS) rates at 1 - 3 years. However, it failed to affect 5-year overall survival (OS) and DFS rates. In the subgroup analyses, different RFA approaches

had significantly higher local recurrence rates than the LH group. A similar effect on OS and DFS rates within five years for single early (3 cm) HCCs and on the 1- and 5-year DFS rates for nodules 5 cm were observed between the two groups, but RFA approaches could reduce the 3-y OS and DFS rates for single nodules 5 cm. The percutaneous radiofrequency ablation (PRFA) group had signif-icantly lower 3- and 5-year OS and the 1- and 3-year DFS rates than the LH group, while no significant difference in OS and DFS rates in the laparoscopic radiofrequency ablation (LRFA) approach. The RFA approach improved the 3-year OS compared with the LH group in Japan, but reduced the 3-year OS and DFS rates within 3 years in China.

Conclusions: Our results support that LH treating sHCC had a better long-term efficacy and a lower local recurrence rate than RFA in the East Asian population. Further high-quality prospective studies are required to confirm the long-term efficacy.



  1. Zhu ZX, Huang JW, Liao MH, Zeng Y. Treatment strategy for hepatocellular carcinoma in China: Radiofrequency ablation versus liver resection. Jpn J Clin Oncol. 2016;46(12):1075-80. doi: 10.1093/jjco/hyw134. [PubMed: 27677661].
  2. Crocetti L. Radiofrequency ablation versus resection for small hepatocellular carcinoma: Are randomized controlled trials still needed? Radiology. 2018;287(2):473-5. doi: 10.1148/radiol.2018172822. [PubMed: 29668405].
  3. Zhu GQ, Sun M, Liao WT, Yu WH, Zhou SL, Zhou ZJ, et al. Comparative efficacy and safety between ablative therapies or surgery for small hepatocellular carcinoma: A network meta-analysis. Expert Rev Gastroenterol Hepatol. 2018;12(9):935-45. doi: 10.1080/17474124.2018.1503531. [PubMed: 30025486].
  4. Li L, Zhang J, Liu X, Li X, Jiao B, Kang T. Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: A meta-analysis. J Gastroenterol Hepatol. 2012;27(1):51-8. doi: 10.1111/j.1440-1746.2011.06947.x. [PubMed: 22004366].
  5. Jafri W, Kamran M. Hepatocellular carcinoma in Asia: A challenging situation. Euroasian J Hepatogastroenterol. 2019;9(1):27-33. doi: 10.5005/jp-journals-10018-1292. [PubMed: 31988864]. [PubMed Central: PMC6969322].
  6. Sarin SK, Kumar M, Eslam M, George J, Al Mahtab M, Akbar SMF, et al. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2020;5(2):167-228. doi: 10.1016/S2468-1253(19)30342-5. [PubMed: 31852635]. [PubMed Central: PMC7164809].
  7. Jiang B, Yan XF, Zhang JH. Meta-analysis of laparoscopic versus open liver resection for hepatocellular carcinoma. Hepatol Res. 2018;48(8):635-63. doi: 10.1111/hepr.13061. [PubMed: 29330919].
  8. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update. Hepatol Int. 2017;11(4):317-70. doi: 10.1007/s12072-017-9799-9. [PubMed: 28620797]. [PubMed Central: PMC5491694].
  9. Okabe H, Yoshizumi T, Yamashita YI, Imai K, Hayashi H, Nakagawa S, et al. Histological architectural classification determines recurrence pattern and prognosis after curative hepatectomy in patients with hepatocellular carcinoma. PLoS One. 2018;13(9). e0203856. doi: 10.1371/journal.pone.0203856. [PubMed: 30216361]. [PubMed Central: PMC6138409].
  10. Zamora-Valdes D, Taner T, Nagorney DM. Surgical treatment of hepatocellular carcinoma. Cancer Control. 2017;24(3):1.0732748177293E+15. doi: 10.1177/1073274817729258. [PubMed: 28975836]. [PubMed Central: PMC5937244].
  11. Casaccia M, Santori G, Bottino G, Diviacco P, Andorno E. Laparoscopic resection vs laparoscopic radiofrequency ablation for the treatment of small hepatocellular carcinomas: A single-center analysis. World J Gastroenterol. 2017;23(4):653-60. doi: 10.3748/wjg.v23.i4.653. [PubMed: 28216972]. [PubMed Central: PMC5292339].
  12. Vitali GC, Laurent A, Terraz S, Majno P, Buchs NC, Rubbia-Brandt L, et al. Minimally invasive surgery versus percutaneous radio frequency ablation for the treatment of single small (Surg Endosc. 2016;30(6):2301-7. doi: 10.1007/s00464-015-4295-6. [PubMed: 26534770].
  13. Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150(4):835-53. doi: 10.1053/j.gastro.2015.12.041. [PubMed: 26795574].
  14. Ito T, Tanaka S, Iwai S, Takemura S, Hagihara A, Uchida-Kobayashi S, et al. Outcomes of laparoscopic hepatic resection versus percutaneous radiofrequency ablation for hepatocellular carcinoma located at the liver surface: A case-control study with propensity score matching. Hepatol Res. 2016;46(6):565-74. doi: 10.1111/hepr.12592. [PubMed: 26386248].
  15. Benson AB, 3rd, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, et al. NCCN guidelines insights: Hepatobiliary cancers, version 1.2017. J Natl Compr Canc Netw. 2017;15(5):563-73. doi: 10.6004/jnccn.2017.0059. [PubMed: 28476736]. [PubMed Central: PMC5557008].
  16. Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008;48 Suppl 1:S20-37. doi: 10.1016/j.jhep.2008.01.022. [PubMed: 18304676].
  17. Yamashita YI, Imai K, Kaida T, Yamao T, Tsukamoto M, Nakagawa S, et al. Multimodal radiofrequency ablation versus laparoscopic hepatic resection for the treatment of primary hepatocellular carcinoma within Milan criteria in severely cirrhotic patients: Long-term favorable outcomes over 10 years. Surg Endosc. 2019;33(1):46-51. doi: 10.1007/s00464-018-6264-3. [PubMed: 29872945].
  18. Yazici P, Akyuz M, Yigitbas H, Dural C, Okoh A, Aydin N, et al. A comparison of perioperative outcomes in elderly patients with malignant liver tumors undergoing laparoscopic liver resection versus radiofrequency ablation. Surg Endosc. 2017;31(3):1269-74. doi: 10.1007/s00464-016-5105-5. [PubMed: 27444839].
  19. Si MB, Yan PJ, Hao XY, Du ZY, Tian HW, Yang J, et al. Efficacy and safety of radiofrequency ablation versus minimally invasive liver surgery for small hepatocellular carcinoma: A systematic review and meta-analysis. Surg Endosc. 2019;33(8):2419-29. doi: 10.1007/s00464-019-06784-0. [PubMed: 30989373].
  20. Li X, Wu YS, Chen D, Lin H. Laparoscopic hepatectomy versus radiofrequency ablation for hepatocellular carcinoma: A systematic review and meta-analysis. Cancer Manag Res. 2019;11:5711-24. doi: 10.2147/CMAR.S189777. [PubMed: 31417314]. [PubMed Central: PMC6600087].
  21. Casaccia M, Santori G, Bottino G, Diviacco P, Negri AD, Moraglia E, et al. The procedure outcome of laparoscopic resection for 'small' hepatocellular carcinoma is comparable to vlaparoscopic radiofrequency ablation. J Minim Access Surg. 2015;11(4):231-5. doi: 10.4103/0972-9941.144093. [PubMed: 26622111]. [PubMed Central: PMC4640020].
  22. Cheung TT, Chan ACY, Chok KSH, Lo CM. Laparoscopic liver resection versus percutaneous radiofrequency ablation in patients with hepatocellular carcinoma and liver cirrhosis: A case-matched study. Lancet. 2017;390. doi: 10.1016/s0140-6736(17)33177-x.
  23. Lin MX, Peng ZW, Chen SL, Dai ZH, Wei GY, Kuang M. Laparoscopic surgery versus radiofrequency ablation for the treatment of recurrent hepatocellular carcinoma: a propensity score matching study. Hepatol Int. 2017;11(1):67. doi: 10.1007/s12072-016-9783-9.
  24. Song J, Wang Y, Ma K, Zheng S, Bie P, Xia F, et al. Laparoscopic hepatectomy versus radiofrequency ablation for minimally invasive treatment of single, small hepatocellular carcinomas. Surg Endosc. 2015;30(10):4249-57. doi: 10.1007/s00464-015-4737-1. [PubMed: 26715020].
  25. Chong CC, Lee KF, Chu CM, Chan AW, Yu SC, Lai PB. Laparoscopic hepatectomy (with or without robotic assistance) versus radiofrequency ablation as a minimally invasive treatment for very early-stage or early-stage hepatocellular carcinoma. Dig Surg. 2020;37(1):65-71. doi: 10.1159/000497112. [PubMed: 30917378].
  26. Moher D, Liberati A, Tetzlaff J, Altman DG, Prisma Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ. 2009;339:b2535. doi: 10.1136/bmj.b2535. [PubMed: 19622551]. [PubMed Central: PMC2714657].
  27. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693-9. doi: 10.1056/NEJM199603143341104. [PubMed: 8594428].
  28. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: Expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394-403. doi: 10.1053/jhep.2001.24563. [PubMed: 11391528].
  29. Xu ZJ, Xu GL, Ma JL, Jia WD, Ge YS, Pan TT. [Ultrasound guided percutaneous radiofrequency ablation versus laparoscopic hepatectomy for small primary liver cancer]. Chin J Gen Surg. 2017;26:18-24. Chinese.
  30. Song JX, Chen J, Li JW. [Clinical analysis of laparoscopic hepatectomy and radiofrequency ablation in the treatment of early hepatocellular carcinoma]. J Hepatobiliary Surg. 2017;25:349-53. Chinese.
  31. Cui HX, Wang Y, Gao Y, Ren JP. [Ultrasound-guided radipfrequency ablation combined with anhydrous ethanol injection versus laparoscopic hepatectomy for small hepatocellular carcinoma]. J Chin Pract Diagn Ther. 2019;33:700-3. Chinese.
  32. Zhou SX, Chen YJ, Yin XB, Ying FM, Feng XF. [The comparison of efficacy between laparoscopic radiofrequency ablation and laparoscopic hepatectomy in the treatment of small hepatic carcinoma]. J Laparosc Surg. 2019;24(4):258-62. Chinese.
  33. Fan XK, Shi LJ, Guo L. [Comparison of laparoscopic-guided radiofrequency ablation and laparoscopic hepatectomy for the treatment of hepatocellular carcinoma]. J Clin Exp Med. 2018;17(14):1540-4. Chinese.
  34. Wu CB, Cao H, Yu H, Wei FL, Wan P. [Effect of laparoscopic hepatectomy and laparoscopic radiofrequency ablation on small hepatocellular carcinoma]. Jiangxi Med J. 2019;54(4):348-51. Chinese.
  35. Zhang HY, Zhuang ZB, Lin CD, Su ZY, Wang T. [Efficacy and prognosis comparison of percutaneous radiofrequency ablation and laparoscopic hepatectomy in treatment of small hepatocellular carcinoma]. Chin J of Gen Surg. 2019;28(1):24-30. Chinese.
  36. Lai C, Jin RA, Liang X, Cai XJ. Comparison of laparoscopic hepatectomy, percutaneous radiofrequency ablation and open hepatectomy in the treatment of small hepatocellular carcinoma. J Zhejiang Univ Sci B. 2016;17(3):236-46. doi: 10.1631/jzus.B1500322. [PubMed: 26984844]. [PubMed Central: PMC4794515].
  37. Harada N, Maeda T, Yoshizumi T, Ikeda T, Kayashima H, Ikegami T, et al. Laparoscopic liver resection is a feasible treatment for patients with hepatocellular carcinoma and portal hypertension. Anticancer Res. 2016;36(7):3489-97. [PubMed: 27354613].
  38. Jiang S, Wang Z, Ou M, Pang Q, Fan D, Cui P. Laparoscopic versus open hepatectomy in short- and long-term outcomes of the hepatocellular carcinoma patients with cirrhosis: A systematic review and meta-analysis. J Laparoendosc Adv Surg Tech A. 2019;29(5):643-54. doi: 10.1089/lap.2018.0588. [PubMed: 30702362].
  39. Deng ZC, Jiang WZ, Tang XD, Liu SH, Qin L, Qian HX. Laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma in 157 patients: A case controlled study with propensity score matching at two Chinese centres. Int J Surg. 2018;56:203-7. doi: 10.1016/j.ijsu.2018.06.026. [PubMed: 29935365].
  40. Buell JF, Thomas MT, Rudich S, Marvin M, Nagubandi R, Ravindra KV, et al. Experience with more than 500 minimally invasive hepatic procedures. Ann Surg. 2008;248(3):475-86. doi: 10.1097/SLA.0b013e318185e647. [PubMed: 18791368].
  41. Dagher I, Belli G, Fantini C, Laurent A, Tayar C, Lainas P, et al. Laparoscopic hepatectomy for hepatocellular carcinoma: A European experience. J Am Coll Surg. 2010;211(1):16-23. doi: 10.1016/j.jamcollsurg.2010.03.012. [PubMed: 20610244].
  42. Zhang W, Wang X, Wang Y, Zhao X, Duan W, Wang Q, et al. Effective viral suppression is necessary to reduce hepatocellular carcinoma development in cirrhotic patients with chronic hepatitis B: Results of a 10-year follow up. Medicine (Baltimore). 2017;96(44). e8454. doi: 10.1097/MD.0000000000008454. [PubMed: 29095292]. [PubMed Central: PMC5682811].
  43. Hikspoors J, Peeters M, Kruepunga N, Mekonen HK, Mommen GMC, Kohler SE, et al. Human liver segments: Role of cryptic liver lobes and vascular physiology in the development of liver veins and left-right asymmetry. Sci Rep. 2017;7(1):17109. doi: 10.1038/s41598-017-16840-1. [PubMed: 29214994]. [PubMed Central: PMC5719430].
  44. Tian ZQ, Su XF, Lin ZY, Wu MC, Wei LX, He J. Meta-analysis of laparoscopic versus open liver resection for colorectal liver metastases. Oncotarget. 2016;7(51):84544-55. doi: 10.18632/oncotarget.13026. [PubMed: 27811369]. [PubMed Central: PMC5356680].
  45. Mariani NM, Santambrogio R, Barabino M, Scifo G, Giovenzana MOE. Laparoscopic liver resection vs radiofrequency ablation in cirrhotic patients with hepatocellular carcinoma: towards the ‘gold standard’. Surg Endosc. 2017;31(2):912-6. doi: 10.1007/s00464-016-5054-z. [PubMed: 27357926].
  46. Wang Y, Luo Q, Li Y, Deng S, Wei S, Li X. Radiofrequency ablation versus hepatic resection for small hepatocellular carcinomas: A meta-analysis of randomized and nonrandomized controlled trials. PLoS One. 2014;9(1). e84484. doi: 10.1371/journal.pone.0084484. [PubMed: 24404166]. [PubMed Central: PMC3880302].
  47. Weis S, Franke A, Mossner J, Jakobsen JC, Schoppmeyer K. Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma. Cochrane Database Syst Rev. 2013;(12). CD003046. doi: 10.1002/14651858.CD003046.pub3. [PubMed: 24357457].
  48. Adachi E, Maeda T, Kajiyama K, Kinukawa N, Matsumata T, Sugimachi K, et al. Factors correlated with portal venous invasion by hepatocellular carcinoma: Univariate and multivariate analyses of 232 resected cases without preoperative treatments. Cancer. 1996;77(10):2022-31. doi: 10.1002/(SICI)1097-0142(19960515)77:10<2022::AID-CNCR9>3.0.CO;2-S. [PubMed: 8640665].
  49. Kong J, Kong L, Kong J, Ke S, Gao J, Ding X, et al. After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma. J Transl Med. 2012;10:230. doi: 10.1186/1479-5876-10-230. [PubMed: 23171368]. [PubMed Central: PMC3543343].
  50. Podnos YD, Henry G, Ortiz JA, Ji P, Cooke J, Cao S, et al. Laparoscopic ultrasound with radiofrequency ablation in cirrhotic patients with hepatocellular carcinoma: Technique and technical considerations. Am Surg. 2001;67(12):1181-4. [PubMed: 11768826].