Clinical Outcomes of Complete Response to Immunotherapy in Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

The advent of immune checkpoint inhibitors (ICIs) has fundamentally altered the treatment landscape for advanced hepatocellular carcinoma (HCC). Nevertheless, complete responses (CRs) are rarely observed, and their long-term outcomes remain incompletely delineated. This investigation explores the clinical consequences, pathologic associations, and most effective management protocols for HCC patients who achieve CR with ICI-based therapy. We performed a retrospective evaluation of 160 individuals with advanced HCC who achieved CR (70 by mRECIST; 90 by RECIST v1.1) following ICI treatment at 4 tertiary referral centers. Assessed endpoints included recurrence-free survival (RFS), overall survival (OS), and pathological verification of imaging-based CR. Multivariable Cox regression was used to determine factors associated with RFS. CR was documented in 4.8% of the total treated population. This group displayed remarkably favorable survival, with 3-year OS and RFS rates reaching 86% and 55%, respectively. Among 8 subjects who underwent operative resection or hepatic transplantation, 6 (75%) exhibited a pathological complete response—2 within the CR-RECIST v1.1 group and 4 in the CR-mRECIST-only category—thereby affirming the fidelity of imaging. Multivariable assessment disclosed macrovascular invasion (aHR 2.47, P = 0.003) and the presence of extrahepatic metastases (aHR 2.00, P = 0.011) as independent predictors of autonomous recurrence, whereas attaining CR per RECIST v1.1 was associated with improved RFS (aHR 0.62, P = 0.015). Individuals who persisted with ICI administration for ≥ 6 months beyond CR had superior 3-year RFS (81% versus 55%, P = 0.002). Of the 11 subjects who proceeded to curative conversion interventions (resection/transplantation/ablation), 92% remained alive at 3 years with a 75% RFS rate. Although infrequent, CR after ICI therapy corresponds with exceptional survival durations in advanced HCC, even among subsets with high-risk features. CR determined by mRECIST demonstrates sound pathological agreement, allaying concerns regarding anti-angiogenic confounding factors. Maintaining ICI treatment for an extended period after CR, combined with judicious use of conversion therapy, may maximize outcomes. These insights reshape prognostic models and stress the imperative for biomarker-informed approaches to preserve disease remission.