The role of circulating tumor DNA in precision adjuvant therapy for colorectal cancer: a scoping review.

Recurrence of colorectal cancer (CRC) after curative-intent treatment is largely driven by minimal residual disease (MRD). Circulating tumor DNA (ctDNA) offers a noninvasive approach to detect MRD and tailor adjuvant therapy and surveillance. This scoping review synthesized prospective cohorts, interventional/randomized trials, and real-world registries on ctDNA-based MRD testing in resected CRC, comparing tumor-informed vs plasma-only (mutation- and/or methylation-based) assays. Postoperative ctDNA positivity strongly predicts recurrence and often precedes radiologic relapse by 3 to 10 months.

Tumor-informed assays provide high specificity and analytical sensitivity, whereas plasma-only assays enable tissue-free, faster testing but often require serial sampling. In stage II colon cancer, ctDNA-guided management reduced the use of chemotherapy without compromising recurrence-free survival. ctDNA dynamics add prognostic resolution. Clearance after adjuvant therapy is associated with excellent outcomes, whereas persistent positivity signals a very high relapse risk. Escalation approaches tested to date (eg, intensified chemotherapy or trifluridine/tipiracil) have not shown definitive disease-free survival gains in patients with a positive ctDNA.

Implementation data indicate that ctDNA can influence treatment and surveillance decisions.

However, barriers include assay variability, optimal timing, counseling, and reimbursement. ctDNA-based MRD testing is a robust prognostic tool and a practical framework for biology-guided postoperative CRC care. Ongoing phase III trials should establish standardized algorithms and effective MRD-directed therapies.