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Peer-reviewedCC BYCurrent oncology (Toronto, Ont.)

Circulating Tumor DNA (ctDNA) for Minimal Residual Disease (MRD) Detection in Colorectal Cancer (CRC): Current Evidence, Clinical Applications, and Future Directions.

5 affiliations
  1. 1Medical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada.
  2. 2School of Natural Sciences, Laurentian University, Sudbury, ON P3E 2C6, Canada.
  3. 3Health Sciences North Research Institute, Sudbury, ON P3E 2H2, Canada.
  4. 4Health Sciences North, Sudbury, ON P3E 2H2, Canada.
  5. 5Clinical Sciences Division, NOSM University, 935 Ramsey Lake Rd., Sudbury, ON P3E 2C6, Canada.

Abstract

Minimal residual disease (MRD) is a major contributor to colorectal cancer (CRC) recurrence following curative-intent treatment, yet conventional surveillance methods may fail to detect residual disease at its earliest stages. Circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker for MRD detection and postoperative monitoring. We conducted a structured PubMed-based literature review and included 94 publications evaluating ctDNA in CRC. Across the literature, postoperative ctDNA positivity was consistently associated with increased recurrence risk and poorer disease-free and overall survival, while serial monitoring improved detection sensitivity and enabled assessment of treatment response. ctDNA frequently identified molecular recurrence approximately 2.5-11.5 months before conventional surveillance. Both tumor-informed and tumor-naive strategies were represented, using PCR/ddPCR, targeted next-generation sequencing, whole-exome or whole-genome sequencing, methylation-based assays, and emerging multiomic approaches. Although ctDNA demonstrates strong prognostic value, evidence supporting treatment modification based solely on ctDNA status remains limited. Further prospective randomized trials, assay standardization, and consensus clinical guidelines are required before routine implementation. Overall, ctDNA is a promising tool for recurrence prediction, surveillance, and precision management of CRC.

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BibTeX
@article{hyde2026circulating,
  title = {{Circulating Tumor DNA (ctDNA) for Minimal Residual Disease (MRD) Detection in Colorectal Cancer (CRC): Current Evidence, Clinical Applications, and Future Directions.}},
  author = {Hannah Hyde and Emma Mageau and Chelsea M Leduc and Mitul J Madhu and Noah Dickinson and Tafheem-Un Nisa and Karolina M Czajka and Stacey A Santi and Prashant Jani and Grace W Ma and Sujeenthar Tharmalingam},
  journal = {Current oncology (Toronto, Ont.)},
  year = {2026},
  month = oct,
  doi = {10.3390/curroncol33100606},
  url = {https://europepmc.org/article/MED/42930172},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Circulating Tumor DNA (ctDNA) for Minimal Residual Disease (MRD) Detection in Colorectal Cancer (CRC): Current Evidence, Clinical Applications, and Future Directions.
AU  - Hannah Hyde
AU  - Emma Mageau
AU  - Chelsea M Leduc
AU  - Mitul J Madhu
AU  - Noah Dickinson
AU  - Tafheem-Un Nisa
AU  - Karolina M Czajka
AU  - Stacey A Santi
AU  - Prashant Jani
AU  - Grace W Ma
AU  - Sujeenthar Tharmalingam
PY  - 2026
DA  - 2026/10/09
JO  - Current oncology (Toronto, Ont.)
DO  - 10.3390/curroncol33100606
UR  - https://europepmc.org/article/MED/42930172
AB  - Minimal residual disease (MRD) is a major contributor to colorectal cancer (CRC) recurrence following curative-intent treatment, yet conventional surveillance methods may fail to detect residual disease at its earliest stages. Circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker for MRD detection and postoperative monitoring. We conducted a structured PubMed-based literature review and included 94 publications evaluating ctDNA in CRC. Across the literature, postoperative ctDNA positivity was consistently associated with increased recurrence risk and poorer disease-free and overall survival, while serial monitoring improved detection sensitivity and enabled assessment of treatment response. ctDNA frequently identified molecular recurrence approximately 2.5-11.5 months before conventional surveillance. Both tumor-informed and tumor-naive strategies were represented, using PCR/ddPCR, targeted next-generation sequencing, whole-exome or whole-genome sequencing, methylation-based assays, and emerging multiomic approaches. Although ctDNA demonstrates strong prognostic value, evidence supporting treatment modification based solely on ctDNA status remains limited. Further prospective randomized trials, assay standardization, and consensus clinical guidelines are required before routine implementation. Overall, ctDNA is a promising tool for recurrence prediction, surveillance, and precision management of CRC.
SN  - 1198-0052
SN  - 1718-7729
ER  -