Background ctDNA is a promising biomarker in oncology. However, its prognostic and predictive value in HCC remains underexplored. This meta-analysis aims to evaluate the prognostic impact of ctDNA in HCC and its predictive value for recurrence. Methods A systematic review and meta-analysis were performed following PRISMA guidelines. PubMed, Embase, Web of Science, and CNKI were searched up to 1 June 2025, for studies assessing ctDNA in HCC patients with reported survival outcomes or predictive accuracy. Studies reporting hazard ratios for overall or disease-free survival, or AUCs for prediction, were included. Two reviewers independently screened studies and assessed quality using the Newcastle-Ottawa Scale (NOS). Meta-analyses used random- or fixed-effects models depending on heterogeneity, with sensitivity analyses performed to assess robustness. Results A total of 219 records were screened from PubMed, Embase, Web of Science, and CNKI, and 8 studies comprising 1,907 patients were included. ctDNA positivity was significantly associated with poorer OS, with a pooled HR of 2.34 (95% CI 1.96–2.78; p 0.0001). Moderate heterogeneity was observed (I 2 = 32.2%). Sensitivity analyses confirmed the robustness of this finding. Two studies assessed the predictive value of ctDNA for RFS, yielding a pooled AUC of 0.66 (95% CI 0.47–0.86; I 2 = 65.7%). Discriminative accuracy was higher when ctDNA was detected postoperatively (AUC range: 0.57–0.77), suggesting its potential role in identifying minimal residual disease. Conclusion ctDNA is associated with adverse prognosis in HCC and may offer moderate predictive accuracy for recurrence. Standardized protocols for sampling and analysis are required to facilitate broader clinical translation.
Wu et al. (Wed,) studied this question.