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Systematic review and meta-analysis of studies assessing circulating tumor DNA kinetics in metastatic colorectal cancer
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DOI：10.1016/j.esmogo.2026.100314.png)
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Abstract
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Background: Circulating tumor DNA (ctDNA) kinetics have emerged as a promising biomarker for monitoring treatment response in metastatic colorectal cancer (mCRC). We carried out a systematic review and meta-analysis to comprehensively assess the prognostic value of ctDNA kinetics during palliative systemic therapy, aiming to consolidate the current evidence and clarify its potential role in clinical practice. Materials and methods: PubMed, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched (last search 12 September 2025). Eligible studies assessed the association between ctDNA kinetics and outcomes in patients with mCRC receiving systemic palliative treatment. Meta-analyses were carried out to evaluate associations with survival outcomes. Results: A total of 64 studies, including data from >2760 patients with mCRC receiving palliative systemic therapy, met the eligibility criteria. Across studies, unfavorable ctDNA kinetics were consistently associated with poorer outcomes, including shorter overall survival (OS) [pooled hazard ratio (HR) 2.6, 95% confidence interval (CI) 2.2-3.2, n = 1086] and progression-free survival (PFS) (pooled HR 2.7, 95% CI 2.4-3.1, n = 1093). Conclusion: ctDNA kinetics during palliative systemic therapy have strong prognostic value in mCRC. However, clinical implementation is hampered by methodological heterogeneity, particularly the use of study-specific ctDNA markers and non-validated cut-offs. Standardized and externally validated approaches are needed to support clinical implementation.
Keywords:
circulating tumor DNA
metastatic colorectal cancer
systemic palliative treatment
ctDNA Response Evaluation Criteria in Solid Tumors
systematic review
meta-analysis
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