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World J Gastroenterol. Jan 14, 2027; 33(2): 122833
Published online Jan 14, 2027. doi: 10.3748/wjg.122833
Prognostic impact of neoadjuvant therapy vs upfront surgery in patients with huge hepatocellular carcinoma undergoing curative resection
Meng-Ran Lang, Ru-Yu Han, Feng-Yi Zhu, Zhi-Hao Wang, Jian-Xin Zhai, Man Luo, Yao-Wei Hu, Chang-Cheng Tao, Ta-Na Siqin, Ji Sun, Zhi-Yu Lu, Jian-Jun Zhao, Jun-Xiang Tong, Xun Wang, Da-Yong Cao, Li-Ming Wang, Wei-Qi Rong, Jian-Xiong Wu, Xuan Meng, Hong-Guang Wang
Meng-Ran Lang, Zhi-Hao Wang, Jian-Xin Zhai, Man Luo, Yao-Wei Hu, Chang-Cheng Tao, Ta-Na Siqin, Ji Sun, Zhi-Yu Lu, Jian-Jun Zhao, Jun-Xiang Tong, Xun Wang, Da-Yong Cao, Li-Ming Wang, Wei-Qi Rong, Jian-Xiong Wu, Xuan Meng, Hong-Guang Wang, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical, Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100020, China
Ru-Yu Han, Feng-Yi Zhu, Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Co-first authors: Meng-Ran Lang and Ru-Yu Han.
Co-corresponding authors: Xuan Meng and Hong-Guang Wang.
Author contributions: Lang MR and Han RY contributed equally to this work as co-first authors; Meng X and Wang HG contributed equally to this work as co-corresponding authors; Meng X and Wang HG designed the research study; Lang MR, Han RY and Zhu FY developed the methodology and performed the statistical analysis; Lang MR, Han RY, Wang ZH, Zhai JX, Luo M, Hu YW, Tao CC, Siqin TN, Sun J, Lu ZY, Zhao JJ, Tong JX, Wang X, Cao DY, Wang LM, Rong WQ and Wu JX collected and curated the data; Meng X, Wang HG, Rong WQ and Wu JX provided clinical resources and supervised the study; Lang MR and Han RY wrote the original draft; Zhu FY, Meng X and Wang HG reviewed and edited the manuscript; Lang MR and Han RY prepared the figures and tables; and all authors have read and approved the final manuscript.
AI contribution statement: AI tools (DeepSeek) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by National Natural Science Foundation of China, No. 82473496 and No. 82272963.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No. NCC2025C-401).
Informed consent statement: The retrospective study was ethically reviewed and waived the need for informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The dataset is available from the corresponding author upon request.
Corresponding author: Hong-Guang Wang, MD, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical, Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100020, China.
wanghongguang1972@163.com
Received: May 6, 2026
Revised: June 14, 2026
Accepted: July 3, 2026
Published online: January 14, 2027
Processing time: 192 Days and 18.8 Hours
BACKGROUND
Huge hepatocellular carcinoma (HCC) is associated with a high postoperative recurrence rate and poor long-term survival. The role of neoadjuvant therapy in patients with huge HCC eligible for curative resection remains uncertain.
AIM
To compare long-term outcomes after neoadjuvant therapy vs upfront surgery in huge HCC.
METHODS
This single-center retrospective surgical cohort study included patients with huge HCC who underwent curative liver resection from January 2019 to November 2024. Huge HCC was defined as a maximum tumor diameter ≥ 10 cm on pre-treatment enhanced computed tomography or magnetic resonance imaging. Patients were divided into neoadjuvant therapy and upfront surgery groups. The primary endpoint was recurrence-free survival (RFS), with overall survival (OS) and surgery-related outcomes as secondary endpoints.
RESULTS
A total of 103 patients were included, with 56 in the neoadjuvant therapy group and 47 in the upfront surgery group. After a median follow-up of 30 months, the RFS and OS rates in the neoadjuvant therapy group were superior to those in the upfront surgery group. The 1-year and 3-year RFS rates were 76.8% vs 55.3% and 59.2% vs 41.5%, respectively. The corresponding 1-year and 3-year OS rates were 98.2% vs 87.2% and 88.9% vs 71.7%, respectively. Multivariable analysis identified upfront surgery and lack of postoperative adjuvant therapy as independent risk factors for poorer RFS and OS. Surgery-related outcomes were comparable between groups.
CONCLUSION
In this retrospective surgical cohort study, neoadjuvant therapy was associated with improved survival without significantly increasing perioperative burden in patients with huge HCC.
Core Tip: Huge hepatocellular carcinoma (HCC) is a particularly aggressive form of liver cancer, and surgery alone often fails to prevent early recurrence. Whether treatment before surgery can improve outcomes in these patients remains unclear. In this retrospective study, we compared patients with huge HCC who underwent surgery after neoadjuvant therapy with those who received upfront surgery. Neoadjuvant therapy was associated with better recurrence-free and overall survival, without significantly increasing operative time, blood loss, transfusion, or postoperative hospital stay. The benefit appeared to be greater in patients with aggressive disease features such as vascular invasion, portal vein tumor thrombus, and Barcelona Clinic Liver Cancer stage C disease. These findings suggest that multimodal neoadjuvant therapy may be a useful perioperative strategy for selected patients with huge HCC and warrant further prospective validation.
