Immune Checkpoint Inhibitor–Based Adjuvant Treatment Versus Surveillance in Curatively Treated Hepatocellular Carcinoma: a Systematic Review and Meta‐Analysis

BACKGROUND: Effective adjuvant treatments in resected or ablated hepatocellular carcinoma (HCC) were elusive over the preceding decades. Recently, immune checkpoint inhibitors (ICIs) have been investigated in the adjuvant setting, with conflicting results. METHODS: A systematic literature search was conducted in multiple databases. Studies investigating adjuvant ICIs as monotherapy or combined with tyrosine kinase inhibitors (TKIs) or anti-angiogenics compared with surveillance in resected or ablated HCC were eligible. The primary and secondary outcomes were recurrence-free survival (RFS) and overall survival (OS). The generic inverse-variance method and random-effects model were utilized. RESULTS: Eighteen studies with a total of 3478 patients were included. The adjuvant treatment modalities were "ICI monotherapy" and "ICI plus TKI/anti-angiogenic" in eight and 10 of the studies, respectively. RFS was significantly improved by "all ICI-based" (HR: 0.51, 95% CI: 0.44-0.60, p < 0.001), "ICI monotherapy" (HR: 0.46, 95% CI: 0.35-0.60, p < 0.001), and "ICI-TKI/anti-angiogenic" combinatory (HR: 0.55, 95% CI: 0.45-0.68, p < 0.001) adjuvant treatments, with no difference between the two (p = 0.29). Subgroup analyses showed consistent benefits regardless of curative treatment modalities of resection or ablation, presence of transarterial chemoembolization, and study design. OS was improved by ICI-based adjuvant therapies compared with surveillance (HR: 0.51, 95% CI: 0.40-0.65, p < 0.001). CONCLUSION: Adjuvant ICIs with or without TKI/anti-angiogenics may provide survival benefits in resected or ablated HCC. Yet the results are limited by the observational nature and territoriality of the included studies. The results of global, randomized, controlled, phase III clinical trials with longer follow-up data will inform clinical practice. PROSPERO ID: CRD42025640036.