The Uncertain Role of ctDNA in Colorectal Cancers
Key Points
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Circulating tumor DNA (ctDNA) is a known prognostic biomarker in colorectal cancer, and studies are evaluating its potential as a predictive biomarker to guide adjuvant therapy.
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The DYNAMIC trial found chemotherapy de-escalation based on ctDNA status did not compromise recurrence outcomes in stage 2 colon cancer.
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Ongoing trials investigate whether ctDNA–guided treatment initiation or escalation improves outcomes across broader patient populations, but the current data are insufficient to incorporate this into clinical practice.
ctDNA Trials in Colorectal Cancer
During the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Udhayvir Grewal, MBBS, of Winship Cancer Institute of Emory University, and Lauren Laderman, MD, of Fox Chase Cancer Center, discussed the role of ctDNA in patients with colorectal cancer.
Previously, studies showed that patients with colorectal cancer who were ctDNA–positive after surgery had worse recurrence and survival outcomes, establishing that ctDNA is a prognostic biomarker. However, whether ctDNA is a predictive biomarker that can be used to select patients for initiation or escalation of adjuvant chemotherapy remains unclear.
Looking at available data, the DYNAMIC trial reported that foregoing adjuvant chemotherapy in ctDNA–negative patients with stage 2 colorectal cancer did not compromise recurrence-free survival. The DYNAMIC-III and CIRCULATE-US trials are further investigating ctDNA–guided adjuvant chemotherapy initiation or escalation in higher-risk patients with colon cancer, but have not generated the level of concrete evidence needed to implement ctDNA as a predictive tool in clinical practice, said Dr. Grewal.
Broadly, two things need to happen before ctDNA can be integrated into clinical practice, suggested Dr. Grewal. First, ctDNA assays require further development to improve sensitivity and specificity, and molecular data may need to be incorporated. Second, clinical trials should be refined to directly evaluate ctDNA’s predictive capabilities. “This would involve enrolling the right patient population, asking the right question, and choosing the right end points—the lead investigators on multiple studies, ongoing and planned, have already looked into this and are working on it,” said Dr. Grewal.