The US FDA has granted breakthrough device designation to the Haystack MRD test, a circulating tumor DNA (ctDNA) assay developed by Quest Diagnostics.1 This designation recognizes the test’s potential to significantly improve the management of minimal residual disease (MRD) in patients with stage II colorectal cancer following curative-intent surgical treatment. The test is designed to identify patients who may benefit from adjuvant therapy, a critical decision point in clinical oncology.
MRD refers to the persistence of a small number of cancer cells in the body after surgical resection, which can lead to disease recurrence. Detecting these microscopic remnants early is a major challenge in cancer care. Traditional methods, such as imaging and carcinoembryonic antigen (CEA) testing, often lack the sensitivity to detect disease at its earliest, most treatable stage.
The Haystack MRD test addresses this by leveraging ultrasensitive next-generation sequencing to detect tiny fragments of ctDNA in a patient’s bloodstream. The presence of ctDNA can signal the presence of residual disease months before it would be visible on a CT scan or other imaging modalities.
The FDA’s Breakthrough Devices Program is designed to accelerate the development, assessment, and review of medical devices that provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating conditions. For a test like this, the designation is a crucial step that can help bring the technology to market more quickly, offering clinicians and patients a timelier and more confident tool for treatment decisions.
This designation is timely as it aligns with a growing body of clinical evidence supporting the use of ctDNA-based MRD tests. One of the seminal trials in this area, the DYNAMIC trial (NCT04089631), demonstrated the clinical utility of using ctDNA analysis to guide adjuvant therapy decisions in stage II colon cancer.2 The results of this multicenter randomized controlled trial showed that a ctDNA-guided approach was noninferior to standard treatment with respect to 3-year recurrence-free survival while also significantly reducing the use of adjuvant chemotherapy. This finding is particularly important for patients with low-risk stage II disease for whom the benefit of adjuvant chemotherapy may be minimal compared to the potential for adverse events.
Microscopic, photorealistic image of colorectal cancer cells – Generated with Adobe Firefly
The Haystack MRD test is already available for clinical use as a laboratory-developed test (LDT), but the FDA designation provides a clear regulatory pathway for a broader, potentially reimbursable, use in clinical practice. The test’s high sensitivity and specificity are attributed to its personalized, tumor-informed approach. It is first “trained” on a sample of the patient’s primary tumor to identify up to 70 unique cancer-associated genetic variants. This personalized “fingerprint” is then used to track and detect trace amounts of ctDNA in subsequent blood samples, providing a highly precise and individualized measure of disease status.
Beyond its current use in stage II colorectal cancer, Quest Diagnostics has indicated its commitment to working with the FDA and research partners to validate the test’s utility in a variety of other solid tumors. This includes exploring its role in assessing treatment response, monitoring for recurrence across different cancer types, and its use within pharmaceutical clinical trials. The ability to accurately and noninvasively monitor for disease recurrence is a paradigm-shifting advance in oncology, empowering clinicians to tailor surveillance strategies and potentially intervene earlier when needed.
The integration of advanced genomic testing like the Haystack MRD assay into routine clinical practice represents a significant step toward personalized precision oncology. As the evidence base for ctDNA-guided care expands, such tests have the potential to optimize treatment strategies, reduce unnecessary exposure to toxic therapies, and ultimately improve patient outcomes.