Dr. Cohen on the Timing of ctDNA Testing in Resected Stage I-III CRC

Stacey A. Cohen, MD, associate professor, the Clinical Research Division, Fred Hutchinson Cancer Center, assistant professor, the Division of Oncology, the University of Washington, discusses the investigation of the optimal timing to test for circulating tumor DNA (ctDNA) to detect minimal residual disease (MRD) following surgery in patients with stage I to III colorectal cancer (CRC).

When evaluating ctDNA, the presence of cell-free DNA (cfDNA) following surgery could potentially decrease the sensitivity of an assay used to detect ctDNA. Previously, clinicians typically waited at least 1 month following surgery to detect reliable ctDNA and avoid a false negative in patients with CRC, Cohen says. To better define the optimal timing for ctDNA testing post-resection, investigators conducted a retrospective study on the kinetics of cfDNA and the affect it has on the detection of MRD in patients who were tested with the Signatera ctDNA assay.

The real-world analysis evaluated patients who had received the Signatera tumor-informed ctDNA testing any time after surgery, and investigators extracted data on 14,425 patients with stage I-III CRC with at least 1 ctDNA result. Notably, patients with stage IV disease or rectal cancer were excluded from the study, Cohen notes. Additionally, investigators had fully annotated data on a subset of 450 patients with information on their surgery, chemotherapy, and recurrence.

Data presented at the 2023 Gastrointestinal Cancers Symposium showed that levels of cfDNA were significantly increased in the first 2 weeks after surgery. Although cfDNA levels were variable in the first two weeks, they were consistent in week 3 and beyond, Cohen notes. Testing for ctDNA 2 to 4 weeks following surgery showed similar sensitivity for detecting MRD compared with weeks 4 to 8.

Cohen and colleagues conclude that standard MRD testing windows could start as early as 2 weeks after surgery. It is hoped these findings could be practice changing by allowing clinicians to test for ctDNA earlier in patients with resected CRC, Cohen concludes.