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Comparative Study
. 2025 Aug 6;74(9):283.
doi: 10.1007/s00262-025-04136-7.

Comparing neoadjuvant targeted therapy plus transarterial chemoembolization versus triple therapy including immunotherapy in hepatocellular carcinoma: a Chinese multicentre study

Hao Yu #  1 , Quan Yuan #  2 , Rui Yu #  3 , Rongjie Ye #  4 , Shuqi Yang  5 , Ming Niu  2 , Yunyun Sun  4 , Jingpeng Ke  1 , Liuxing Feng  1 , Ping Guo  1 , Yujian Liu  1 , Jingrui Yang  1 , Zaifa Hong  1 , Taozhu Ye  3 , Weixiang Ni  3 , Xin Wang  6 , Zhenhao Xie  1 , Jiahuan Xu  7 , Chuncheng Lin  8 , Lizhi Lv  9 , Shuangjia Wang  10 , Chao Zhan  11
Affiliations
Comparative Study

Comparing neoadjuvant targeted therapy plus transarterial chemoembolization versus triple therapy including immunotherapy in hepatocellular carcinoma: a Chinese multicentre study

Hao Yu et al. Cancer Immunol Immunother. .

Abstract

Background: Neoadjuvant therapy (NAT) is a promising strategy to improve long-term outcomes in hepatocellular carcinoma (HCC), particularly for patients with borderline resectable. Targeted therapy, transarterial chemoembolization (TACE), immunotherapy, and radiotherapy are all effective NAT strategies for HCC; however, the optimal NAT regimen for HCC remains undefined.

Methods: This multicentre retrospective study included 64 HCC patients who underwent NAT followed by surgical resection between 2020 and 2024 at four tertiary hospitals in China. Based on the treatment regimen, patients were divided into two groups: the dual-therapy group, which received TACE combined with either lenvatinib or bevacizumab, and the triple-therapy group, which additionally received anti-PD-1/PD-L1 immunotherapy. Survival outcomes and prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards models.

Results: The triple-therapy group demonstrated significantly better progression-free survival (PFS) and overall survival (OS) compared to the dual-therapy group (PFS: HR = 0.450, P = 0.048; OS: HR = 0.437, P = 0.039). Multivariate Cox analysis identified triple therapy, lower tumour burden, and higher pathological response as favourable prognostic factors, whereas vascular invasion and elevated alpha-fetoprotein (AFP) levels were linked to poorer outcomes. Additionally, in this Chinese HCC cohort, the China Liver Cancer (CNLC) staging system appeared to provide superior prognostic stratification compared to the Barcelona Clinic Liver Cancer (BCLC) system.

Conclusion: In the context of NAT for HCC, triple therapy-combining TACE, targeted agents, and immunotherapy-appears to be a more effective treatment option compared to dual therapy.

Keywords: China liver cancer staging system; Hepatocellular carcinoma; Immune checkpoint inhibitor; Major pathological response; Neoadjuvant therapy; Transarterial chemoembolization.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval and informed consent. This research was approved by the Institutional Ethics Review Boards of all participating centres: Harbin Medical University Cancer Hospital (KY2024-28), The First Affiliated Hospital of Xiamen University ([2024]133), Quanzhou First Hospital Affiliated to Fujian Medical University (2025-K150), and the 900th Hospital of PLA Joint Logistic Support Force (2024–040). Given that the study was retrospective in nature, the requirement for informed consent was waived.

Figures

Fig. 1
Fig. 1
Flowchart of patient enrolment and exclusion criteria
Fig. 2
Fig. 2
Kaplan–Meier curves comparing OS and PFS between the triple- and dual-therapy groups
Fig. 3
Fig. 3
OS and PFS comparison between early-intermediate and advanced HCC patients based on CNLC staging
Fig. 4
Fig. 4
Kaplan–Meier curves of OS and PFS stratified by pathological response
See this image and copyright information in PMC

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