This review evaluates the clinical utility of circulating tumor DNA (ctDNA) liquid biopsies for monitoring cancer progression, detecting minimal residual disease (MRD), identifying resistance mutations, and guiding treatment decisions across multiple cancer types including NSCLC, colorectal cancer, breast cancer, and urothelial carcinoma.
In a meta-analysis of 1,725 urothelial carcinoma patients, higher ctDNA levels correlated with markedly worse disease-free survival (HR 20.69; 95% CI 9.63–44.43) and overall survival in metastatic settings (HR 2.0; 95% CI 1.25–3.38). In a prospective cohort of 130 colorectal cancer patients, ctDNA detected molecular relapse ~8.7 months earlier than standard imaging (5.5 vs. 14.2 months; P < .001).
Optimal timing of ctDNA testing is not yet defined; management of ctDNA-positive results without radiographic disease remains uncertain; cost-effectiveness of serial ctDNA monitoring has not been established.
ctDNA can flag recurrence months before imaging and help select molecularly targeted therapy — but clinicians should not yet act on positive ctDNA alone without clear protocols, as best practices for result management and monitoring intervals are still being defined.
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