ctDNA as a potential future decision aid Wednesday, October 07, 2026 A follow up correlative study from the CCTG CO28 trial, Tumor-Free Circulating Tumor DNA in Node-Negative Rectal Cancers Undergoing Neoadjuvant Chemotherapy, Excision, and Observation in the Phase II NEO Trial (CO.28) has just been published. The Canadian Cancer Trials Group (CCTG) CO.28 trial demonstrated that neoadjuvant chemotherapy followed by transanal excision was an effective treatment approach for patients with cT1–3, node-negative (N0) rectal cancer. Researchers subsequently explored circulating tumour DNA (ctDNA) from the trial as a potential decision aid to help guide the need for total mesorectal excision (TME). "Finding better ways to safely offer organ preservation is a real priority for patients with early rectal cancer. This CCTG-led study gives us early signals that ctDNA could support those decisions, and it will help inform the correlative science planned for CO.32 NEORT," says the studies PI and CCTG Senior Investigator, Dr. Jonathan Loree. Organ preservation is an important priority in early-stage rectal cancer, as TME can have a significant impact on quality of life. In this analysis, ctDNA testing identified patients with an inadequate response to chemotherapy among those for whom TME was recommended. A tissue-free ctDNA assay may also offer faster turnaround times than tumour-informed assays, potentially providing a practical tool to support organ-preservation decisions. These findings support further evaluation of ctDNA assays in early-stage rectal cancer and their potential role in guiding treatment decisions. Loree JM, Titmuss E, Brown CJ, Rich T, Banks K, Gordon V, Patel S, Krahn M, Caycedo-Marulanda A, Raval M, Tu D, Jonker DJ, O'Callaghan CJ, Kennecke HF. Tumor-Free Circulating Tumor DNA in Node-Negative Rectal Cancers Undergoing Neoadjuvant Chemotherapy, Excision, and Observation in the Phase II NEO Trial (CO.28) (ONLINE). JCO Precis Oncol 10: e2600459. 2026.https://ascopubs.org/doi/abs/10.1200/PO-26-00459 For more information please visit the CO28 trial page.