Haystack MRD Test Demonstrates High Accuracy for Detecting Residual and Recurrent Disease in Colorectal Cancer and Analytical Performance Across Solid Tumors – Quest Diagnostics

 Quest Diagnostics published a new study in The Journal of Molecular Diagnostics showing that the Haystack Mrd test is highly accurate at detecting residual and recurrent disease, demonstrating clinical performance in specimens from the landmark DYNAMIC colorectal cancer trial series.
The study also validated the test’s analytical performance across 23 solid tumor types. Provided by Quest Diagnostics, Haystack Mrd is an ultrasensitive circulating tumor DNA (ctDNA) liquid biopsy test for identifying residual or recurrent disease in patients with solid tumor cancers.

The study evaluated the clinical performance of the commercially available Haystack Mrd test by retrospectively testing residual specimens from patients enrolled in the DYNAMIC and DYNAMIC-III trials, which evaluated the use of ctDNA-based MRD results (generated with an earlier version of the Haystack Mrd technology) to guide chemotherapy decisions in stage II and III colorectal cancer. In this cohort, Haystack Mrd results were highly associated with recurrence, demonstrating 100% sensitivity and 100% specificity at 3-year follow-up and 83.3% sensitivity and 100% specificity at 5-year follow-up. Haystack Mrd also substantially outperformed carcinoembryonic antigen (CEA), a standard blood-based biomarker, detecting recurrence with 88.9% sensitivity versus 11.1% for CEA (median follow-up 60 months).

Scientists from Quest and Haystack Oncology conducted the study together with investigators from the two institutions that led the DYNAMIC trials: The Walter and Eliza Hall Institute of Medical Research and the Peter MacCallum Cancer Center in Melbourne, Australia.

“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.” – Professor Jeanne Tie,* a medical oncologist at Peter MacCallum Cancer Centre and lead investigator for the DYNAMIC trial series.

In other key findings, Haystack Mrd:

-Demonstrated ultrasensitive detection of residual disease, with a 95% limit of detection (LoD95) of 0.063 mean ctDNA molecules per milliliter (mL) of plasma. Earlier validation established an LoD95 of 6 parts per million (PPM), a metric commonly reported for tumor-informed MRD assays1.

-Achieved sub-PPM detection of 0.8 PPM, and as low as 0.2 PPM in some samples, with no false positives in cancer-free controls using an investigational whole-genome version of the test. This whole-genome version is currently only available to clinical investigators and biopharma partners while the commercial test uses whole-exome sequencing.

-Established a limit of quantitation (LOQ) suitable for response monitoring of 0.25 mean ctDNA molecules per mL. Establishing the LOQ allows a change in a patient’s ctDNA level between serial tests to be interpreted as a real change in tumor burden rather than assay variability.

-Demonstrated analytical performance across the complete testing process, starting from plasma collection and including cell free (cf) DNA extraction, rather than starting with already extracted cfDNA. As a result, analytical performance can be directly translated to clinical performance, versus assay validations that begin with extracted cfDNA and do not account for extraction variability.

“To our knowledge, this is the first time that the full ctDNA MRD testing process, starting from plasma collection and including cfDNA extraction, has been characterized for the limit of detection (at 95%) and quantitative analytical performance. The precise quantitative measurements demonstrated in this validation provide confidence that the Haystack Mrd test accurately measures changes in ctDNA levels over time and can be used for serial ctDNA monitoring during and after treatment. With these insights, clinicians can understand the degree of change in ctDNA levels related to tumor biology in an individual patient, supporting earlier evaluation of treatment response and detection of molecular progression or recurrence.” – Dan Edelstein, Vice President and General Manager, Haystack Oncology.

In addition, the study examined a real-world clinical cohort from an Early Experience program in which Haystack Mrd detected ctDNA across 27 solid tumor types, including at ultra-low concentrations, with 42% of positive results below 0.5 mean ctDNA molecules/mL.

The new study adds to the growing body of evidence supporting the clinical value of Haystack Mrd, following two studies published in The New England Journal of Medicine. Published in 2022, DYNAMIC was the first prospective, interventional study to demonstrate the clinical utility of ctDNA-based MRD testing to reduce the use of chemotherapy in stage II colon cancer without compromising recurrence-free survival. In 2025, a study on response to immunotherapy in mismatch repair-deficient cancers found that the Haystack Mrd test was a “reliable liquid biopsy surrogate” that identified clinical complete response at a median of 1.4 months, compared with more than 6 months using imaging.

*Dr. Tie has served as an advisor and consultant for Haystack Oncology.