Circulating tumor DNA (ctDNA) may guide adjuvant treatment after curative-intent therapy and support multicancer early detection (MCED), but prognostic accuracy and clinical utility are distinct.

PRISMA 2020 and PRISMA-S guided a narrative synthesis. MEDLINE/PubMed, Embase, Scopus, Web of Science, CENTRAL, trial registries and citation sources were searched to 31 January 2026. Two reviewers screened records and extracted data independently. Risk of bias and certainty of evidence were appraised descriptively, and no meta-analysis was performed because of heterogeneity in assays, designs and outcomes.

Fifty-four unique records were screened; 29 reports (21 clinical/longitudinal and 8 analytical/diagnostic) were summarized. DYNAMIC reduced chemotherapy use in stage II colon cancer from 28% to 15% with similar five-year recurrence-free survival (88% vs 87%). IMvigor011 improved disease-free survival (hazard ratio 0.64) and overall survival (hazard ratio 0.59) in ctDNA-positive muscle-invasive bladder cancer. DETECT-A and PATHFINDER supported screening-pathway feasibility; SYMPLIFY and THUNDER supplied separate diagnostic context. Mortality benefit was not tested.

ctDNA has clinical utility in selected molecular-residual-disease settings when a prespecified result triggers effective treatment. In most settings it remains prognostic. MCED requires randomized net-benefit, mortality, and harm evaluations before population implementation.