Consensus and controversy of liquid biopsy using circulating tumour DNA (ctDNA) for molecular residual disease detection in colorectal cancer
- 1Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London, Surrey, UK
- 2Corresponding author. Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK.
Abstract
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.
Related
- Risk stratification by circulating tumor DNA-based pretreatment genomic profile and post-operative molecular residual disease detection in resectable colorectal oligometastases: PRECISION, a prospective multicenter study
- Circulating Tumor DNA (ctDNA) for Minimal Residual Disease (MRD) Detection in Colorectal Cancer (CRC): Current Evidence, Clinical Applications, and Future Directions.
- Circulating Tumor DNA in Resected Colorectal Liver Metastases: From Minimal Residual Disease Detection to Treatment Guidance—A Systematic Review
- Circulating Tumor DNA Status and Adjuvant Chemotherapy in Resected Colorectal Liver Metastases
- An exploratory study of circulating cell-free mRNAs across colorectal cancer stages
BibTeX
@article{lefas2026consensus,
title = {{Consensus and controversy of liquid biopsy using circulating tumour DNA (ctDNA) for molecular residual disease detection in colorectal cancer}},
author = {Alicia Yioli Lefas and Ian Chau},
journal = {The Lancet Regional Health. Western Pacific},
year = {2026},
month = oct,
doi = {10.1016/j.lanwpc.2026.102001},
url = {https://doi.org/10.1016/j.lanwpc.2026.102001},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Consensus and controversy of liquid biopsy using circulating tumour DNA (ctDNA) for molecular residual disease detection in colorectal cancer
AU - Alicia Yioli Lefas
AU - Ian Chau
PY - 2026
DA - 2026/10/01
JO - The Lancet Regional Health. Western Pacific
DO - 10.1016/j.lanwpc.2026.102001
UR - https://doi.org/10.1016/j.lanwpc.2026.102001
AB - 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.
SN - 2666-6065
ER -