Background/Aims Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated.
Methods In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated.
Results During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence.
Conclusions Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.
Citations
Citations to this article as recorded by
BCLC strategy for prognosis prediction and treatment recommendations: The 2026 update Maria Reig, Marco Sanduzzi-Zamparelli, Alejandro Forner, Jordi Rimola, Joana Ferrer-Fàbrega, Marta Burrel, Ángeles Garcia-Criado, Alba Díaz, Neus Llarch, Gemma Iserte, Meritxell Mollà, Robin K. Kelley, Peter R. Galle, Vincenzo Mazzaferro, Riad Salem, Brun Journal of Hepatology.2026; 84(3): 631. CrossRef
Long-Term Analysis of Recurrence Beyond Milan Criteria Following Ablation of Solitary Early-Stage Hepatocellular Carcinoma ≤3 cm in Potentially Transplantable Patients: A Over 10-Year Survival Study Shuanggang Chen, Han Qi, Hongtong Tan, Fei Cao, Lin Xie, Tao Huang, Ying Wu, Chunyong Wen, Yujia Wang, Lujun Shen, Weijun Fan Journal of Hepatocellular Carcinoma.2025; Volume 12: 205. CrossRef
Investigation into the efficiency and prognostic elements of CT-guided ¹²⁵I particle implantation for liver cancer Yuxiao Xia, Quanyu Zhou, Xue Jiang, Wenling Tu, Qian Liu, Liangshan Li, Yuhong Shi Cancer Imaging.2025;[Epub] CrossRef
Recurrence patterns and survival outcomes after irreversible electroporation for hepatocellular carcinoma: a 6-year multicenter experience Min Xu, Shanyu Yin, Qiyu Zhao, Guo Tian, Jinhua Pan, Gang Dong, Wu Zhang, Tuerganaili Aji, Jiansong Ji, Xinhua Chen, Danxia Xu, Tian’an Jiang European Radiology.2025; 36(3): 2305. CrossRef
Prognostic model for predicting recurrence in hepatocellular carcinoma patients with high systemic immune-inflammation index based on machine learning in a multicenter study Ningning Lu, Shugui Sheng, Yiqi Xiong, Chuanren Zhao, Wenying Qiao, Xiaoyan Ding, Jinglong Chen, Yonghong Zhang Frontiers in Immunology.2024;[Epub] CrossRef
Risk of Treatment Failure and Death after Ablation in Hepatocellular Carcinoma Patients—A Multiparametric Prediction Sergio Muñoz-Martínez, Victor Sapena, Ángeles García-Criado, Anna Darnell, Alejandro Forner, Ernest Belmonte, Marco Sanduzzi-Zamparelli, Jordi Rimola, Alexandre Soler, Neus Llarch, Gemma Iserte, Ezequiel Mauro, Carmen Ayuso, Jose Rios, Jordi Bruix, Ramon Cancers.2023; 15(13): 3269. CrossRef
Decoding Immune Signature to Detect the Risk for Early-Stage HCC Recurrence Aswathy R. Devan, Bhagyalakshmi Nair, Manu Kanjoormana Aryan, Vijayastelar B. Liju, Joel Joy Koshy, Bijo Mathew, Arun Valsan, Hoon Kim, Lekshmi R. Nath Cancers.2023; 15(10): 2729. CrossRef
Predictive Factors of Treatment Outcomes After Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in the Hepatocaval Confluence: A Propensity Score Matching Analysis Yanzhao Zhou, Kun Yuan, Yi Yang, Xiao Shan, Zemin Ji, Dezheng Zhou, Jingzhong Ouyang, Zhengzheng Wang, Qi Zhang, Jinxue Zhou, Qiang Li Academic Radiology.2023; 30: S92. CrossRef
Risk factors for recurrence beyond Milan criteria after radiofrequency ablation in transplantable small hepatocellular carcinoma Weike Chu, Ping Li, Xue Wu, Peng Zhang, Hui Zhou, Bin Niu Revista Española de Enfermedades Digestivas.2022;[Epub] CrossRef
Surgery versus radiofrequency ablation in patients with Child- Pugh class-A/single small (≤3 cm) hepatocellular carcinoma Jungnam Lee, Young-Joo Jin, Seung Kak Shin, Jung Hyun Kwon, Sang Gyune Kim, Young Ju Suh, Yujin Jeong, Jung Hwan Yu, Jin-Woo Lee, Oh Sang Kwon, Soon Woo Nahm, Young Seok Kim Clinical and Molecular Hepatology.2022; 28(2): 207. CrossRef
Percutaneous thermal ablation combined with transcatheter arterial chemoembolization for hepatitis C virus-related hepatocellular carcinoma: Efficacy and survival Yu Sun, Honghai Zhang, Jiang Long, Yonghong Zhang, Jiasheng Zheng, Chunwang Yuan Frontiers in Oncology.2022;[Epub] CrossRef
Non‐transplantable recurrence after percutaneous thermal ablation of ≤3‐cm HCC: Predictors and implications for treatment allocation Cecilia Gozzo, Margaux Hermida, Astrid Herrero, Fabrizio Panaro, Christophe Cassinotto, Azhar Meerun Mohamad, Eric Assenat, Chloé Guillot, Carole Allimant, Valentina Schembri, Antonio Basile, Sébastien Dharancy, José Ursic‐Bedoya, Boris Guiu Hepatology Communications.2022; 6(10): 2975. CrossRef
Integrated Analysis Revealing the Role Of TET3-Mediated MUC13 Promoter Hypomethylation in Hepatocellular Carcinogenesis Ruijiao Kong, Hui Zhang, Yin Jia, Qiuhong Man, Shanrong Liu Epigenomics.2022; 14(24): 1579. CrossRef
Risk factors of secondary infection/recurrence after ablation for liver cancers: A systemic review and meta-analysis Gang Yin, Nengwei Zhang, AMin BuHe, Wei Yan, Tianxiong Li, Jirun Peng Journal of Cancer Research and Therapeutics.2022; 18(5): 1352. CrossRef
Risk Factors, Patterns, and Long-Term Survival of Recurrence After Radiofrequency Ablation With or Without Transarterial Chemoembolization for Hepatocellular Carcinoma Jingjun Huang, Wensou Huang, Yongjian Guo, Mingyue Cai, Jingwen Zhou, Liteng Lin, Kangshun Zhu Frontiers in Oncology.2021;[Epub] CrossRef
Four types of tumor progression after microwave ablation of single hepatocellular carcinoma of ≤5 cm: incidence, risk factors and clinical significance Zhimei Huang, Zhixing Guo, Jiayan Ni, Mengxuan Zuo, Tianqi Zhang, Rong Ma, Chao An, Jinhua Huang International Journal of Hyperthermia.2021; 38(1): 1164. CrossRef
Radiofrequency ablation with four electrodes as a building block for matrix radiofrequency ablation: Ex vivo liver experiments and finite element method modelling. Influence of electric and activation mode on coagulation size and geometry Stefaan Mulier, Ricardo Possebon, Yansheng Jiang, Jacques Jamart, Chong Wang, Yi Miao, Tongfu Yu, Kuirong Jiang, Yuanbo Feng, Guy Marchal, Luc Michel, Yicheng Ni Surgical Oncology.2020; 33: 145. CrossRef
Long-term outcome of intraoperative radiofrequency ablation for hepatocellular carcinoma and its efficacy as a primary treatment Jongduk Kwon, Kwang-Sik Chun, In-Sang Song, Seok-Hwan Kim, Sunjong Han Annals of Hepato-Biliary-Pancreatic Surgery.2020; 24(1): 24. CrossRef
Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients Jihye Kim, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik Clinical and Molecular Hepatology.2020; 26(4): 516. CrossRef
Predicting outcomes for recurrent hepatocellular carcinoma within Milan criteria after complete radiofrequency ablation Hsin-Yeh Chen, Sheng-Nan Lu, Chao-Hung Hung, Jing-Houng Wang, Chien-Hung Chen, Yi-Hao Yen, Yuan-Hung Kuo, Kwong-Ming Kee, Tatsuo Kanda PLOS ONE.2020; 15(11): e0242113. CrossRef
Feasibility, efficacy, and safety of percutaneous MR‐guided ablation of small (≤12 mm) hepatic malignancies Jakob Weiss, Rüdiger Hoffmann, Hansjoerg Rempp, David‐Emanuel Keβler, Philippe L. Pereira, Konstantin Nikolaou, Stephan Clasen Journal of Magnetic Resonance Imaging.2019; 49(2): 374. CrossRef
Clinical outcomes of patients with a single hepatocellular carcinoma less than 5 cm treated with transarterial chemoembolization Min Young Baek, Jeong-Ju Yoo, Soung Won Jeong, Jae Young Jang, Yong Kwon Kim, Shin Ok Jeong, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, Yong Jae Kim, Su Yeon Park The Korean Journal of Internal Medicine.2019; 34(6): 1223. CrossRef
Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients Adam Doyle, Andre Gorgen, Hala Muaddi, Aloysious D. Aravinthan, Assaf Issachar, Oleg Mironov, Wei Zhang, John Kachura, Robert Beecroft, Sean P. Cleary, Anand Ghanekar, Paul D. Greig, Ian D. McGilvray, Markus Selzner, Mark S. Cattral, David R. Grant, Lesli Journal of Hepatology.2019; 70(5): 866. CrossRef
Clinical and circulating biomarkers of survival and recurrence after radiofrequency ablation in patients with hepatocellular carcinoma Matteo Canale, Paola Ulivi, Francesco Giuseppe Foschi, Emanuela Scarpi, Serena De Matteis, Gabriele Donati, Giorgio Ercolani, Mario Scartozzi, Luca Faloppi, Alessandro Passardi, Emiliano Tamburini, Martina Valgiusti, Giorgia Marisi, Giovanni Luca Frassine Critical Reviews in Oncology/Hematology.2018; 129: 44. CrossRef
A new scoring model predicting macroscopic vascular invasion of early-intermediate hepatocellular carcinoma Yao Liu, Le Sun, Fangyuan Gao, Xue Yang, Yuxin Li, Qun Zhang, Bingbing Zhu, Shuaishuai Niu, Yunyi Huang, Ying Hu, Ying Feng, Yuyong Jiang, Xianbo Wang Medicine.2018; 97(49): e13536. CrossRef
Traitement ablatif pour cancer du rein : modalités d’évaluation pré-, per-, post-intervention et prise en charge adaptée J. Garnon, T. Tricard, R.L. Cazzato, X. Cathelineau, A. Gangi, H. Lang Progrès en Urologie.2017; 27(15): 971. CrossRef
Editorial: rifaximin in cirrhosis—is this what we've been waiting for? Authors’ reply S. H. Kang, Y. B. Lee, J.‐H. Lee Alimentary Pharmacology & Therapeutics.2017; 46(10): 1017. CrossRef
First
Prev
