NEW YORK — In guidelines issued Monday, the US National Comprehensive Cancer Network said post-surgical circulating tumor DNA (ctDNA) is an emerging prognostic marker but does not recommend its use or the use of multigene assays to inform recurrence risk or adjuvant treatment among patients with colon cancer.
The panel said that while ctDNA, multigene assays, and the immune response-based scoring system Immunoscore can provide additional recurrence risk information as compared to other risk factors among colorectal cancer patients, it questioned "the value added." In particular, it noted that these tests have not been shown to be able to predict whether patients may benefit from additional chemotherapy. Instead, the panel suggested additional clinical trials be conducted to gather more data.
For instance, according to the panel, the QUASAR and National Surgical Adjuvant Breast and Bowel Project (NSABP) trials have shown that recurrence scores generated by Exact Sciences' Oncotype DX colon cancer assay, which analyzes the expression of seven recurrence-risk genes and five reference genes, are prognostic for recurrence, disease-free survival, and overall survival in stage II and III colon cancer. However, the NCCN panel noted that the recurrence designation was not predictive of benefit from adjuvant treatment.
It added that one study, the NSABP C-07 trial, suggested that patients with high recurrence scores might have more absolute benefit from the platinum-based chemotherapy oxaliplatin, but that the score did not itself predict oxaliplatin efficacy.
Other gene expression-based multigene assays, like Agendia's ColoPrint and Almac's ColDx, can also classify patients by recurrence risk independently of other recurrence risk factors, the panel said.
Likewise, multiple studies, including the DYNAMIC and GALAXY studies, have indicated that post-surgical ctDNA can gauge disease recurrence risk among stage I, II, and III colon cancer patients. But the NCCN panel said that although the results support the use of ctDNA as a prognostic marker, outstanding questions remain regarding the best timing for conducting testing. There are further drawbacks, it noted, as a positive result without signs of disease is only helpful if there are intervention options.
"[CtDNA] is emerging as a prognostic marker; however, there is currently insufficient evidence to recommend routine use of ctDNA assays outside of a clinical trial," the panel said.
The European Society for Medical Oncology released guidelines in 2020 that also said gene signatures, postoperative ctDNA, and Immunoscore may aid in determining recurrence risk among colon cancer patients, and additionally noted limited data on chemotherapy benefit.
Though the guidelines were specifically about colon cancer testing, Wall Street analysts were quick to note the potential future impact on minimal residual disease testing using ctDNA. According to TD Cowen analyst Dan Brennan, the 2024 guidelines from NCCN "were largely in line with our expectations," adding that eventual guideline changes would be "needle moving" for firms in the MRD testing category.
He said a positive readout from Natera's "ALTAIR trial for therapy escalation should warrant more definitive language for the use of MRD (if positive) in the 2025 update." Brennan specifically cited the impact on Natera over competitors Guardant Health, NeoGenomics, Personalis, and others because its Signatera has a "material lead in peer-reviewed evidence that validates the assay."
He added, "Emerging MRD vendors will need to develop robust clinical evidence including outcomes studies to capture the most value in the coming years."