Postoperative ctDNA-Guided Adjuvant Therapy in Resected Colorectal Cancer: A Systematic Review and Meta-analysis of Prognostic Validity Versus Treatment-Decision Utility.

Postoperative circulating tumor DNA (ctDNA) is a strong marker of molecular residual disease after curative-intent colorectal cancer resection, but prognostic validity alone does not establish treatment-decision utility. We performed a PRISMA 2020 systematic review and meta-analysis with search coverage through March 31, 2026, separating randomized ctDNA-guided treatment-decision evidence from prospective prognostic cohorts, platform-trial evidence, implementation evidence, and ongoing trials. Thirty-eight reports or programs were included in the evidence map, and seven independent prospective cohorts contributed to the prognostic meta-analysis. Postoperative ctDNA positivity was associated with increased recurrence risk (pooled hazard ratio, 7.60; 95% CI, 4.70-12.31), with substantial heterogeneity (I²=80.6%) and a wide prediction interval (1.60-36.25). Decision evidence was scenario-specific: DYNAMIC supports consideration of selective stage II colon cancer de-escalation, whereas DYNAMIC-III did not establish non-inferiority for routine stage III de-escalation. Current evidence does not support routine empiric escalation for MRD-positive disease. Postoperative ctDNA should therefore be interpreted as a powerful risk-stratification tool whose treatment-changing role remains limited to selected clinical contexts.