新辅助治疗在可切除性肝细胞癌管理中的探索和挑战

doi:10.3969/j.issn.1006-5725.2025.23.022

Abstract

Abstract:

Neoadjuvant therapy for hepatocellular carcinoma is the frontier and hot topic in the current field of liver cancer research. The fundamental purpose is to reduce the risk of postoperative recurrence through standardized preoperative treatment methods. From the attempts of Transcatheter Arterial Chemoembolization monotherapy for neoadjuvant therapy for hepatocellular carcinoma to systematic treatment represented by “targeted combined with immunotherapy”， the latter has become the most promising neoadjuvant strategy due to its high objective response rate and potential to induce pathological complete remission. However， the field still faces challenges such as lack of evidence of overall survival benefit in Phase Ⅲ randomized controlled trials， treatment-related adverse reactions that may lead to delay in surgery， optimal population screening， and timing of surgery. This article aims to briefly discuss the current research status of the application of neoadjuvant therapy in resectable hepatocellular carcinoma， explore relevant diagnosis and treatment concepts， and further understand neoadjuvant therapy.

Key words: hepatocellular carcinoma, neoadjuvant therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, molecular targeted therapy, immunotherapy

CLC Number:

R735.7

Xin LIU,Yutao HE,Fangming TIAN,Haocheng TANG,Zhitian SHI,Lin. WANG. Exploration and challenges of neoadjuvant therapy in the management of resectable hepatocellular carcinoma[J]. The Journal of Practical Medicine, 2025, 41(23): 3780-3785.

References 49

[1]	NIERENGARTEN M B. Global cancer statistics 2022： The report offers a view on disparities in the incidence and mortality of cancer by sex and region worldwide and on the areas needing attention［J］. Cancer， 2024， 130（15）： 2568. doi:10.1002/cncr.35444 doi: 10.1002/cncr.35444
[2]	BRAY F， LAVERSANNE M， SUNG H， et al. Global cancer statistics 2022： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin， 2024， 74（3）： 229-63. doi:10.3322/caac.21834 doi: 10.3322/caac.21834
[3]	GLANTZOUNIS G K， KORKOLIS D， SOTIROPOULOS G C， et al. Individualized Approach in the Surgical Management of Hepatocellular Carcinoma： Results from a Greek Multicentre Study［J］. Cancers， 2022， 14（18）： 4387. doi:10.3390/cancers14184387 doi: 10.3390/cancers14184387
[4]	GARCES C A， CANCE W G. Neoadjuvant chemotherapy of breast cancer［J］. Am Surg， 2004， 70（7）： 565-569. doi:10.1177/000313480407000701 doi: 10.1177/000313480407000701
[5]	沈未，鲁迪，徐骁. 肝癌肝移植适应证的科学演进［J］. 器官移植， 2025， 16（2）： 202-207.
[6]	TOHME S， SIMMONS R L， TSUNG A. Surgery for Cancer： A Trigger for Metastases［J］. Cancer Res， 2017， 77（7）： 1548-1552. doi:10.1158/0008-5472.can-16-1536 doi: 10.1158/0008-5472.can-16-1536
[7]	TANG F， TIE Y， TU C， et al. Surgical trauma-induced immunosuppression in cancer： Recent advances and the potential therapies［J］. Clin Transl Med， 2020， 10（1）： 199-223. doi:10.1002/ctm2.24 doi: 10.1002/ctm2.24
[8]	BAKOS O， LAWSON C， ROULEAU S， et al. Combining surgery and immunotherapy： Turning an immunosuppressive effect into a therapeutic opportunity［J］. J Immunother Cancer， 2018， 6（1）： 86. doi:10.1186/s40425-018-0398-7 doi: 10.1186/s40425-018-0398-7
[9]	李文锋，李建华，王正昕. 肝癌肝移植术前应用免疫检查点抑制剂治疗的进展［J］. 器官移植， 2025， 16（3）： 329-337.
[10]	王花，黑悦，孙淼，等. 贝伐珠单抗联合雷替曲塞治疗不可切除肝细胞癌的疗效及对不良反应和生存率影响［J］. 实用医学杂志， 2024， 40（21）： 3061-3066.
[11]	CHANG Y， JEONG S W， YOUNG JANG J， et al. Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma［J］. Int J Mol Sci， 2020， 21（21）： 8165. doi:10.3390/ijms21218165 doi: 10.3390/ijms21218165
[12]	UESHIMA K， KOMEMUSHI A， ARAMAKI T， et al. Clinical Practice Guidelines for Hepatic Arterial Infusion Chemotherapy with a Port System Proposed by the Japanese Society of Interventional Radiology and Japanese Society of Implantable Port Assisted Treatment［J］. Liver Cancer， 2022， 11（5）： 407-425. doi:10.1159/000524893 doi: 10.1159/000524893
[13]	BAE S H， CHUN S J， CHUNG J H， et al. Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma： Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines［J］. Int J Radiat Oncol Biol Phys， 2024， 118（2）： 337-351. doi:10.1016/j.ijrobp.2023.08.015 doi: 10.1016/j.ijrobp.2023.08.015
[14]	YOSHIDA T， SAKON M， UMESHITA K， et al. Appraisal of transarterial immunoembolization for hepatocellular carcinoma： A clinicopathologic study［J］. J Clin Gastroenterol， 2001， 32（1）： 59-65. doi:10.1097/00004836-200101000-00014 doi: 10.1097/00004836-200101000-00014
[15]	QI X， LIU L， WANG D， et al. Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma： A systematic review and meta-analysis［J］. Oncotarget， 2015， 6（34）： 36838-36859. doi:10.18632/oncotarget.5426 doi: 10.18632/oncotarget.5426
[16]	AMISAKI M， HONJO S， MORIMOTO M， et al. The Negative Effect of Preoperative Transcatheter Arterial Chemoembolization on Long-Term Outcomes for Resectable Hepatocellular Carcinoma： A Propensity Score Matching Analysis［J］. Yonago Acta Med， 2016， 59（4）： 270-278.
[17]	PAIK K Y， KIM E K. Pathologic response to preoperative transarterial chemoembolization for resectable hepatocellular carcinoma may not predict recurrence after liver resection［J］. Hepatobiliary Pancreat Dis Int， 2016， 15（2）： 158-164. doi:10.1016/s1499-3872(15)60042-x doi: 10.1016/s1499-3872(15)60042-x
[18]	LI C， WANG M D， LU L， et al. Preoperative transcatheter arterial chemoembolization for surgical resection of huge hepatocellular carcinoma （≥ 10 cm）： A multicenter propensity matching analysis［J］. Hepatol Int， 2019， 13（6）： 736-747. doi:10.1007/s12072-019-09981-0 doi: 10.1007/s12072-019-09981-0
[19]	GIANNONE F， FELLI E， CIPRIANI F， et al. Prognostic benefit of preoperative transarterial chemoembolization in upfront resectable large hepatocellular carcinoma： A multicentric propensity score based analysis of European high-volume centers［J］. HPB（Oxford）， 2024， 26（6）： 840-850. doi:10.1016/j.hpb.2024.03.1159 doi: 10.1016/j.hpb.2024.03.1159
[20]	BI X， ZHAO H， ZHAO H， et al. Consensus of Chinese Experts on Neoadjuvant and Conversion Therapies for Hepatocellular Carcinoma： 2023 Update［J］. Liver Cancer， 2025， 14（2）： 223-238.
[21]	SHI M， LU L G， FANG W Q， et al. Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma： Single-blind， randomized trial［J］. J Natl Cancer Inst， 2013， 105（1）： 59-68. doi:10.1093/jnci/djs464 doi: 10.1093/jnci/djs464
[22]	LI S H， MEI J， CHENG Y， et al. Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion： A Multicenter， Phase III， Randomized Study［J］. J Clin Oncol， 2023， 41（10）： 1898-1908. doi:10.1200/jco.22.01142 doi: 10.1200/jco.22.01142
[23]	HU Z， YANG Z， WANG J， et al. Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus［J］. Front Pharmacol， 2023， 14：1223632. doi:10.3389/fphar.2023.1223632 doi: 10.3389/fphar.2023.1223632
[24]	CHIANG C L， CHEN Y C， LIANG H L， et al. Survival outcomes after surgical resection of huge HCC （≥ 10 cm） with or without neoadjuvant hepatic arterial infusion chemotherapy［J］. World J Surg Oncol， 2025， 23（1）： 251. doi:10.1186/s12957-025-03876-1 doi: 10.1186/s12957-025-03876-1
[25]	HU Z， DENG M， FU Y， et al. Neoadjuvant hepatic arterial infusion of oxaliplatin， fluorouracil， and leucovorin for resectable single large hepatocellular carcinoma［J］. Int J Surg， 2025， 111（6）： 3850-3858. doi:10.1097/js9.0000000000002437 doi: 10.1097/js9.0000000000002437
[26]	TAO C， WU F， LIU Y， et al. Long-term outcome of centrally located hepatocellular carcinoma treated by neoadjuvant radiotherapy and radical resection： A propensity score matched study［J］. Ann Med Surg （Lond）， 2024， 86（1）： 78-84. doi:10.1097/ms9.0000000000001489 doi: 10.1097/ms9.0000000000001489
[27]	YU W B， RAO A， VU V， et al. Management of centrally located hepatocellular carcinoma： Update 2016［J］. World J Hepatol， 2017， 9（13）： 627-634. doi:10.4254/wjh.v9.i13.627 doi: 10.4254/wjh.v9.i13.627
[28]	WU F， CHEN B， DONG D， et al. Phase 2 Evaluation of Neoadjuvant Intensity-Modulated Radiotherapy in Centrally Located Hepatocellular Carcinoma： A Nonrandomized Controlled Trial［J］. JAMA Surg， 2022， 157（12）： 1089-1096. doi:10.1001/jamasurg.2022.4702 doi: 10.1001/jamasurg.2022.4702
[29]	WEI X， JIANG Y， FENG S， et al. Neoadjuvant intensity modulated radiotherapy for a single and small （≤ 5 cm） hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion： A randomized clinical trial［J］. Int J Surg， 2023， 109（10）： 3052-3060. doi:10.1097/js9.0000000000000574 doi: 10.1097/js9.0000000000000574
[30]	WEI X， JIANG Y， ZHANG X， et al. Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus： A Randomized， Open-Label， Multicenter Controlled Study［J］. J Clin Oncol， 2019， 37（24）： 2141-2151. doi:10.1200/jco.18.02184 doi: 10.1200/jco.18.02184
[31]	FONTANA A P， RUSSOLILLO N， MAURINO L， et al. Impact of Preoperative Yttrium-90 Transarterial Radioembolization on Patients Undergoing Right or Extended Right Hepatectomy for Hepatocellular Carcinoma［J］. Cancers （Basel）， 2025， 17（15）： 2556. doi:10.3390/cancers17152556 doi: 10.3390/cancers17152556
[32]	FINN R S， QIN S， IKEDA M， et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma［J］. N Engl J Med， 2020， 382（20）： 1894-1905. doi:10.1056/nejmoa1915745 doi: 10.1056/nejmoa1915745
[33]	TAZDAIT M， MEZQUITA L， LAHMAR J， et al. Patterns of responses in metastatic NSCLC during PD-1 or PDL-1 inhibitor therapy： Comparison of RECIST 1.1， irRECIST and iRECIST criteria［J］. Eur J Cancer， 2018， 88： 38-47. doi:10.1016/j.ejca.2017.10.017 doi: 10.1016/j.ejca.2017.10.017
[34]	MARRON T U， FIEL M I， HAMON P， et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma： A single-arm， open-label， phase 2 trial［J］. Lancet Gastroenterol Hepatol， 2022， 7（3）： 219-229. doi:10.1016/s2468-1253(21)00385-x doi: 10.1016/s2468-1253(21)00385-x
[35]	CHEUNG T T， WAI-HUNG HO D， LYU S X， et al. Multimodal Integrative Genomics and Pathology Analyses in Neoadjuvant Nivolumab Treatment for Intermediate and Locally Advanced Hepatocellular Carcinoma［J］. Liver Cancer， 2024， 13（1）： 70-88. doi:10.1159/000531176 doi: 10.1159/000531176
[36]	KASEB A O， HASANOV E， CAO H S T， et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma： A randomised， open-label， phase 2 trial［J］. Lancet Gastroenterol Hepatol， 2022， 7（3）： 208-218. doi:10.1016/s2468-1253(21)00427-1 doi: 10.1016/s2468-1253(21)00427-1
[37]	TABRIZIAN P， MARINO R， BHOORI S， et al. Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma［J］. JHEP Rep， 2025， 7（2）： 101246. doi:10.1016/j.jhepr.2024.101246 doi: 10.1016/j.jhepr.2024.101246
[38]	HOFFMANN K， GANTEN T， GOTTHARDTP D， et al. Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC patients - a prospective， randomized， double-blind， phase Ⅲ trial［J］. BMC Cancer， 2015， 15： 392. doi:10.1186/s12885-015-1373-z doi: 10.1186/s12885-015-1373-z
[39]	SANGRO B， KUDO M， ERINJERI J P， et al. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma （EMERALD-1）： A multiregional， randomised， double-blind， placebo-controlled， phase 3 study［J］. Lancet， 2025， 405（10474）： 216-232.
[40]	KUDO M， REN Z， GUO Y， et al. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable， non-metastatic hepatocellular carcinoma （LEAP-012）： A multicentre， randomised， double-blind， phase 3 study［J］. Lancet， 2025， 405（10474）： 203-215. doi:10.1016/s0140-6736(24)02575-3 doi: 10.1016/s0140-6736(24)02575-3
[41]	WU J Y， WU J Y， LI Y N， et al. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence： A multicenter retrospective study［J］. Front Oncol， 2022， 12： 985380. doi:10.3389/fonc.2022.985380 doi: 10.3389/fonc.2022.985380
[42]	XIA Y， TANG W， QIAN X， et al. Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma： A single-arm， open label， phase Ⅱ clinical trial［J］. J Immunother Cancer， 2022， 10（4）：e004656. doi:10.1136/jitc-2022-004656 doi: 10.1136/jitc-2022-004656
[43]	BO W， ZHANG L， CHEN Y， et al. Neoadjuvant therapy with triple therapy for centrally located hepatocellular carcinoma［J］. Eur J Surg Oncol， 2025， 51（5）： 109588. doi:10.1016/j.ejso.2025.109588 doi: 10.1016/j.ejso.2025.109588
[44]	LI Z， LIU J， ZHANG B， et al. Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma： The Notable-HCC phase 1b trial［J］. Nat Commun， 2024， 15（1）： 3260. doi:10.1038/s41467-024-47420-3 doi: 10.1038/s41467-024-47420-3
[45]	谢海翔，韩创业，彭凯，等. 肝动脉灌注化疗联合免疫靶向新辅助治疗单发CNLC Ⅰb期肝细胞癌的安全性与疗效分析［J］. 中华肝胆外科杂志， 2023， 29（1）： 28-33.
[46]	HO W J， ZHU Q， DURHAM J， et al. Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumor Immunity［J］. Nat Cancer， 2021， 2（9）： 891-903. doi:10.1038/s43018-021-00234-4 doi: 10.1038/s43018-021-00234-4
[47]	HAO Y， XIE F， ZHOU Y， et al. Neoadjuvant therapy of sequential TACE， camrelizumab， and apatinib for single huge hepatocellular carcinoma （NEO-START）： Study protocol for a randomized controlled trial［J］. Trials， 2024， 25（1）： 490. doi:10.1186/s13063-024-08340-1 doi: 10.1186/s13063-024-08340-1
[48]	LAPELUSA M， CHAMSEDDINE S， TRAN CAO H S， et al. Tissue and Imaging Biomarkers of Response to Neoadjuvant Nivolumab or Nivolumab plus Ipilimumab in Patients with Resectable Hepatocellular Carcinoma［J］. Oncology， 2025， 103（6）： 490-497. doi:10.1159/000541250 doi: 10.1159/000541250
[49]	蔡惠亮，张乾营，黄莹，等. 增强MRI瘤内瘤周影像组学联合临床影像学特征评估肝细胞癌ki-67的表达［J］. 实用医学杂志， 2025， 41（15）： 2311-2319.

Exploration and challenges of neoadjuvant therapy in the management of resectable hepatocellular carcinoma

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 49

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Yue LV,Yanna MENG,Panpan LI,Yinghong. CHEN. Value of SWD in preoperative assessment of liver fibrosis in patients with hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2025, 41(5): 751-755.
[2]	Kui XU,Jun. ZHOU. Research progress of ultrasound microbubbles in diagnosis and treatment of thyroid cancer [J]. The Journal of Practical Medicine, 2025, 41(3): 454-458.
[3]	Zongjian HU,Shun WAN,Jianwei YANG,Li WANG,Siyu CHEN,Li YANG. Research progress of CAR⁃T cell therapy in bladder cancer [J]. The Journal of Practical Medicine, 2025, 41(22): 3496-3500.
[4]	Hang LI,Xiaomei YANG,Wen LYU,Huimin CHEN,Rui. XU. Three⁃year evaluation of the efficacy and safety of chronotherapy in dual⁃allergen subcutaneous immunotherapy [J]. The Journal of Practical Medicine, 2025, 41(21): 3405-3411.
[5]	Ya CHEN,Xiaoyong LUO,Yinghua CHEN,Yawen. LUO. Expression of HBV RNA in hepatitis B virus⁃associated hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2025, 41(21): 3435-3441.
[6]	Wei YANG,Xiahai LIANG,Huidong XIA,Ru. BAI. The expression of TUBB2A in HCC and its effect on malignant biological behaviors of HCC cells under hypoxia [J]. The Journal of Practical Medicine, 2025, 41(20): 3175-3184.
[7]	Qiang FU,Zhongqi LU,Ying CHANG,Tiefeng JIN,Meihua. ZHANG. Research progress on the antitumor effects of immune checkpoint inhibitors [J]. The Journal of Practical Medicine, 2025, 41(2): 288-293.
[8]	Muying HUANG,Chu LIU,Jiaman LIU,Zhicong. WANG. Early identification of high⁃risk children who develop systemic adverse reactions related to dust mite allergy subcutaneous immunotherapy [J]. The Journal of Practical Medicine, 2025, 41(19): 3065-3071.
[9]	Lingchun CAO,Fanliang MENG,Xiaoan SHENG. Risk factors and model construction of immune therapy⁃related thyroid dysfunction in non⁃small cell lung cancer [J]. The Journal of Practical Medicine, 2025, 41(17): 2705-2714.
[10]	Mengying ZHANG,Yaokai MA,Yifan DU,Wei ZHANG,Bo ZHOU,Xiyi YANG. A Randomized controlled study on the efficacy of HAIC sequential DEB⁃TACE in the treatment of colorectal cancer liver metastasis [J]. The Journal of Practical Medicine, 2025, 41(17): 2721-2728.
[11]	Min MO,Jingjing LIN,Xin LU,Jin. LU. The predictive value of contrast‑enhanced ultrasound parameters combined with serum CXCL9 and IGFBP‑3 for recurrence of hepatocellular carcinoma after interventional therapy [J]. The Journal of Practical Medicine, 2025, 41(16): 2568-2574.
[12]	Zhaoyang WANG,Nan. ZHANG. Constructing a Nomogram prediction model for early recurrence of hepatocellular carcinoma radical hepatectomy based on CT imaging omics and traditional Chinese medicine tongue image features [J]. The Journal of Practical Medicine, 2025, 41(16): 2590-2596.
[13]	Huiliang CAI,Qianying ZHANG,Ying HUANG,Weisheng PENG,Chengli WANG,Cuiting YANG,Na DENG,Sizhu ZHANG,Nina XU,Xiaobing HAN. Assessments of ki⁃67 expression in hepatocellular carcinoma using enhanced MRI intratumoral and peritumoral radiomics and clinical imaging features [J]. The Journal of Practical Medicine, 2025, 41(15): 2311-2319.
[14]	Caifang GUO,Hong FAN,Ting LUAN,Hui ZHAN,Haifeng WANG,Jiansong WANG. The role and research progress of cytoreductive nephrectomy in metastatic renal cell carcinoma [J]. The Journal of Practical Medicine, 2025, 41(13): 1952-1957.
[15]	Zegong HU,Yan BAI. Research advances in allergen-specific immunotherapy [J]. The Journal of Practical Medicine, 2025, 41(11): 1760-1766.