ArticleFrontiers in oncology2025
Imaging-defined complete response to immune checkpoint inhibitors predicts durable survival in advanced hepatocellular carcinoma.
Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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