Blood-Based MRD Test Shows High Specificity in Colorectal Cancer Trials

Circulating tumor DNA (ctDNA) testing offers a blood-based way to detect remaining disease, but assays must identify very small amounts of tumor DNA while maintaining high specificity. Carcinoembryonic antigen (CEA) remains a standard blood-based biomarker in this setting. Addressing the need for more sensitive blood-based monitoring, a newly evaluated liquid biopsy test has shown strong clinical performance in specimens from the DYNAMIC colorectal cancer trials.

Haystack MRD from Quest Diagnostics (Secaucus, NJ, USA) is an ultrasensitive ctDNA liquid biopsy test designed to identify minimal residual disease (MRD) or recurrent disease in patients with solid tumors. The tumor-informed, next-generation assay detects ultralow levels of ctDNA, with the commercial test using whole-exome sequencing. It was developed and validated in a CLIA-certified laboratory and is commercially available as a laboratory-developed test. In 2025, the U.S. Food and Drug Administration (FDA) granted Haystack MRD Dx Breakthrough Device Designation for stage II colorectal cancer, and the test is authorized for patient access in all 50 U.S. states.

A study published in The Journal of Molecular Diagnostics evaluated the commercially available assay by retrospectively testing residual specimens from patients enrolled in the DYNAMIC and DYNAMIC-III trials. These trials used ctDNA-based residual disease results generated with an earlier version of the technology to guide chemotherapy decisions in stage II and III colorectal cancer. Haystack MRD demonstrated 100% sensitivity and 100% specificity at three-year follow-up, and 83.3% sensitivity with 100% specificity at five-year follow-up. For detecting recurrence, the assay achieved 88.9% sensitivity, compared with 11.1% for CEA at a median follow-up of 60 months.

The study also validated analytical performance across 23 solid tumor types and assessed the complete testing process from plasma collection through cell-free DNA extraction. The assay achieved a 95% limit of detection of 0.063 mean ctDNA molecules per milliliter of plasma and a limit of quantitation of 0.25 mean ctDNA molecules per milliliter. An investigational whole-genome version achieved detection at 0.8 parts per million, and as low as 0.2 parts per million in some samples, with no false positives among cancer-free controls. In an Early Experience program, the test detected ctDNA across 27 solid tumor types, with 42% of positive results measuring below 0.5 mean ctDNA molecules per milliliter.

Earlier studies published in The New England Journal of Medicine included the 2022 DYNAMIC trial and a 2025 study evaluating immunotherapy response in mismatch repair-deficient cancers.

“The DYNAMIC trial demonstrated the potential for ctDNA to guide more individualized treatment decisions in stage II colon cancer but realizing that potential depends on a highly sensitive assay that can reliably detect the extremely small amounts of tumor DNA that may remain after treatment, while maintaining high specificity. This study helps bridge the gap between clinical research and real-world patient care,” said Professor Jeanne Tie, a medical oncologist at Peter MacCallum Cancer Centre and lead investigator for the DYNAMIC trial series.

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