ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
This article is part of the Research TopicNovel Insights into the Tumor Microenvironment's Role in Liver Cancer Occurrence and RecurrenceView all articles
Imaging-Defined Complete Response to Immune Checkpoint Inhibitors Predicts Durable Survival in Advanced Hepatocellular Carcinoma
Provisionally accepted
- 1Graduate School, Dalian Medical University, Dalian 116044, Liaoning, China, Dalian, Liaoning, China
- 2Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
- 3Southern University of Science and Technology, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Immune checkpoint inhibitors (ICIs) have revolutionized advanced hepatocellular carcinoma (HCC) treatment, yet complete responses (CRs) remain rare, and their long-term outcomes are poorly characterized. This study evaluates clinical outcomes, pathologic correlates, and optimal management strategies for HCC patients achieving CR to ICI-based therapy. Methods: We retrospectively analyzed 160 patients with advanced HCC who attained CR (70 by mRECIST; 90 by RECIST v1.1) following ICI therapy at four tertiary centers. Outcomes included recurrence-free survival (RFS), overall survival (OS), and pathologic validation of radiographic CR. Multivariable Cox models identified predictors of RFS. Results: CRs occurred in 4.8% of treated patients. The cohort demonstrated exceptional survival, with 3-year OS and RFS rates of 86% and 55%, respectively. Among the 8 patients who underwent resection or liver transplantation, 6 (75%) achieved pathologic complete response, 2 in the CR-RECISTv1.1 group and 4 in the CR-mRECIST-only group, supporting imaging validity. Multivariable analysis revealed presence of macrovascular invasion (aHR 2.47, p=0.003) and presence of extrahepatic metastases (aHR 2.00, p=0.011) as independent risk factors for recurrence, while CR by RECIST v1.1 predicted improved RFS (aHR 0.62, p=0.015). Patients continuing ICI ≥6 months post-CR had superior 3-year RFS (81% vs. 55%, p=0.002). Of 11 patients undergoing curative conversion therapy (resection/transplantation/ablation), 92% survived at 3 years with 75% RFS. Conclusions: CR to ICI therapy, though uncommon, correlates with unprecedented survival in advanced HCC, even among high-risk subgroups. mRECIST-defined CR shows strong pathologic concordance, addressing concerns about anti-angiogenic confounders. Extended ICI duration post-CR and selective conversion therapy may optimize outcomes. These findings redefine prognostic paradigms and underscore the need for biomarker-driven strategies to sustain remission.
Keywords: complete response, Hepatocellular Carcinoma, immune checkpoint inhibitors, mRECIST, Survival outcomes
Received: 17 Aug 2025; Accepted: 19 Dec 2025.
Copyright: © 2025 Shao, Yuan, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Feng Wang
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.