Consensus and controversy of liquid biopsy using circulating tumour DNA (ctDNA) for molecular residual disease detection in colorectal cancer.

Circulating tumour DNA (ctDNA) detection after curative-intent treatment is one of the strongest prognostic biomarkers in colorectal cancer (CRC), but its clinical utility remains incompletely established. Randomised trials have shown that ctDNA-informed management can reduce adjuvant chemotherapy exposure in selected stage II colon cancer, yet non-inferiority was not established in stage III disease, and cytotoxic escalation for ctDNA-positive molecular residual disease (MRD) has not improved recurrence-free survival. These mixed interventional results do not diminish the prognostic validity of ctDNA, but suggest that its clinical utility depends on four interacting considerations: the biological state represented by ctDNA positivity, the timing of testing and intervention, assay and sampling heterogeneity, and trial design. Serial ctDNA dynamics may provide additional biological and prognostic information, as sustained clearance, transient clearance, persistence, and re-emergence are unlikely to represent equivalent states of MRD. Western Pacific studies have led the field, including GALAXY and ALTAIR in Japan and Taiwan, DYNAMIC in Australia, FIND and CINTS-R in China, and CLAUDIA in Korea. However, regional implementation is constrained by uneven laboratory infrastructure, cost, regulatory access, and limited evidence from Southeast Asia and Pacific lower-resource settings. Outside clinical trials, ctDNA should refine prognosis rather than dictate omission, intensification, or initiation of treatment. Future trials should align assay performance, biological timing, and intervention mechanism, and use patient-centred endpoints capable of demonstrating that acting on ctDNA improves outcomes.