NCCN Enhances ctDNA Guidance for Colon, Rectal, and Merkel Cell Cancers
Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, has recently commented on the updated guidelines by the National Comprehensive Cancer Network (NCCN) regarding circulating tumor DNA (ctDNA) molecular residual disease (MRD) testing for colon cancer, rectal cancer, and Merkel cell carcinoma (MCC). This update marks a significant advancement in the use of ctDNA as a prognostic tool for cancer recurrence.
For the first time, the NCCN has officially recognized ctDNA as a high-risk factor for recurrence in the adjuvant setting for both colon and rectal cancer. This recognition represents a major step forward in incorporating ctDNA testing as a prognostic tool. The updated guidelines now recommend ctDNA as a high-risk marker for recurrence in these cancers, reflecting its ability to predict the likelihood of relapse.
Despite this progress, the guidelines remain cautious about using ctDNA for surveillance purposes, as further research is required to confirm its efficacy in long-term monitoring. The updated guidelines were finalized before the results of the phase III CALGB (Alliance) / SWOG 80702 study were presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in January, which supported the predictive value of Signatera in the adjuvant setting.
For Merkel cell carcinoma (MCC), a rare but aggressive form of skin cancer, the NCCN guidelines now state that ctDNA testing can be used to assess disease burden in both virus-positive and virus-negative MCC patients. The test typically becomes positive before or at the time of clinically evident recurrence, making it a valuable tool for early detection of relapse.
Furthermore, the guidelines highlight a publication from 2024 in the Journal of Clinical Oncology (JCO), which demonstrated the strong performance of Signatera in MCC patients. According to the study, Signatera achieved 95% detection at the time of enrollment and showed a 20-fold higher risk of recurrence among patients who were persistently ctDNA positive. These findings underscore the clinical utility of ctDNA testing in monitoring MCC patients and may pave the way for broader applications in other cancer indications.
“Signatera tumor-informed ctDNA testing is an invaluable prognostic tool for surveillance in high- and low-risk MCC patients. It helps physicians determine appropriate imaging frequency based on the likelihood of recurrence,” said Dr. Lisa Zaba, associate professor of dermatology at Stanford University and director of the MCC multi-disciplinary clinic. Her statement further emphasizes the importance of ctDNA testing in improving clinical outcomes and guiding treatment strategies for MCC patients.
MCC is a rare but highly aggressive skin cancer, with approximately 3,000 cases diagnosed annually in the United States. The disease disproportionately affects the elderly, with most patients being diagnosed after the age of 70. MCC has a high mortality rate, and the recurrence rate within five years can reach 40%. Early detection of recurrence is crucial for improving patient outcomes, making ctDNA testing an essential tool for managing this challenging disease.
“These guideline updates came sooner than anticipated, reflecting the growing recognition of ctDNA’s role in cancer care,” said Dr. Alexey Aleshin, Natera’s Chief Medical Officer and General Manager of Oncology. “The inclusion of ctDNA testing for colon, rectal, and MCC cancers is a critical step towards more personalized, targeted care for cancer patients.”
About Signatera
Signatera is a personalized, tumor-informed molecular residual disease test designed for patients who have previously been diagnosed with cancer. By analyzing circulating tumor DNA, Signatera helps detect and quantify remaining cancer in the body, identify recurrence earlier than traditional diagnostic methods, and optimize treatment decisions. Signatera is clinically validated across multiple cancer types and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer, and muscle-invasive bladder cancer, as well as for monitoring response to immunotherapy in any solid tumor. The test has been featured in over 100 peer-reviewed publications, demonstrating its effectiveness in cancer monitoring.
About Natera
Natera is a global leader in cell-free DNA and genetic testing, with a focus on oncology, women’s health, and organ health. Natera is committed to making personalized genetic testing a standard part of healthcare, providing tools for earlier, more precise interventions that can lead to better health outcomes. With over 250 peer-reviewed publications supporting the accuracy of its tests, Natera operates ISO 13485-certified and CAP-accredited laboratories in Austin, Texas, and San Carlos, California.
