Circulating tumor DNA and recurrence after curative-intent treatment of hepatocellular carcinoma: A systematic review and meta-analysis.
Abstract
Background
Recurrence after curative-intent treatment remains common in HCC. Circulating tumor DNA (ctDNA) may provide prognostic information, but evidence is heterogeneous.
Methods
We reviewed 12 cohort studies (880 patients) with HCC treated with curative intent. Associations of preoperative or postoperative ctDNA detection with recurrence-free survival (RFS) or overall survival (OS) were synthesized. Treatment-modality subgroup analyses were performed; assay-platform and sampling-time analyses were not performed because studies were insufficiently comparable. Risk of bias was assessed using QUIPS and QUADAS-2, and certainty using GRADE. Meta-analyses used generic inverse-variance pooling in RevMan 5.4; leave-one-out analyses used log hazard ratios and standard errors in Stata 17.
Results
Preoperative ctDNA detection was associated with worse RFS (HR 3.34, 95% CI 1.99-5.63; 4 studies, 291 patients; moderate certainty). Postoperative ctDNA detection was associated with worse RFS (HR 4.95, 95% CI 2.77-8.83; 11 studies, 799 patients; low certainty; I2 = 79%) and OS (HR 3.07, 95% CI 1.80-5.23; 3 studies, 357 patients; low certainty). Exploratory diagnostic accuracy for subsequent recurrence was modest (8 studies, 508 patients; very-low certainty).
Conclusion
ctDNA detection was associated with recurrence after curative-intent treatment, but heterogeneity, small-study effects, risk-of-bias concerns, and prospective validation restrict clinical applicability. Routine use is not yet supported.