Circulating tumor DNA in colorectal cancer: from prognostic insight to emerging clinical standard

Summary Liquid biopsy using circulating tumor DNA (ctDNA) has become one of the most promising approaches in precision oncology, offering a minimally invasive means to track tumor burden, detect minimal residual disease, and monitor treatment response in real time. In colorectal cancer (CRC), ctDNA has been investigated extensively across both localized and advanced disease. In localized CRC, ctDNA testing after surgery provides strong prognostic value, with positivity indicating a high risk of recurrence and negativity correlating with favorable long-term outcomes. ctDNA dynamics during adjuvant therapy can further refine risk stratification, as clearance is associated with improved survival, while persistence signals poor prognosis. Moreover, ctDNA-guided strategies in the adjuvant setting have demonstrated potential to enable safe treatment de-escalation or intensification, tailoring therapy to individual patient risk. In the neoadjuvant setting, particularly in rectal cancer, ctDNA has shown promise as a predictor of pathological response and long-term outcomes, raising the possibility of guiding organ-preserving or intensified treatment strategies. In metastatic CRC, ctDNA serves as a dynamic biomarker for baseline profiling, real-time monitoring of treatment response, and detection of emerging resistance mechanisms, supporting adaptive therapeutic decision-making throughout the disease course. Despite its promise, challenges remain, including variability across assay platforms, risk of false negatives in low-volume disease, lack of standardized thresholds for intervention, and questions of cost-effectiveness. Collectively, ctDNA represents a transformative biomarker in CRC, with ongoing research and harmonization efforts expected to establish its role as a clinical standard for guiding precision treatment.