Haystack MRD Test Earns FDA Breakthrough Device Designation in Stage II CRC

Data presented at the 2025 ASCO Annual Meeting revealed that the evaluation of circulating tumor DNA (ctDNA) using the MRD test correlated with improved response assessment to neoadjuvant treatment in patients with esophageal cancer.

The FDA has granted breakthrough device designation to the Haystack MRD® test for the identification of patients with minimal residual disease (MRD)–positive stage II colorectal cancer (CRC) after surgical treatment with curative intent who may benefit from adjuvant therapy based on therapeutic labeling, according to a news release from the assay’s developer, Quest Diagnostics.¹

Previously, the developers launched a clinical laboratory-developed test version of the Haystack MRD test in late 2024. Since then, they have been expanding access to the test among oncologists as well as pharmaceutical partners. Furthermore, in early August 2025, they announced a collaboration with researchers from Mass General Brigham to investigate the use of the assay as an aid in postoperative therapy decisions in cutaneous squamous cell carcinoma (CSCC) and head and neck squamous cell carcinoma (HNSCC).²

Furthermore, data presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meetingrevealed that the evaluation of circulating tumor DNA (ctDNA) using the MRD test correlated with improved response assessment to neoadjuvant treatment in patients with esophageal cancer.³ Specifically, ctDNA positivity following neoadjuvant therapy was strongly associated with poor pathological response (P = .0026).

Among 20 pre- and post-neoadjuvant samples, ctDNA was detected in 100% of patients vs 45% of patients, respectively. In 5 patients with ctDNA-positive status, 100% experienced disease recurrence or death, with a median time from ctDNA positivity to event of 14.4 months (range, 0.1-24.5). Additionally, among 10 patients with ctDNA-negative status upon testing, 70% were disease-free at follow-up, with a median follow-up of 46.7 months (range, 6.3-65.5).

Patients in the analysis presented at ASCO had plasma samples collected between September 2017 and April 2023. A total of 66% of patients had received neoadjuvant chemoradiation, and 51% underwent prior surgery.

“We are committed to working with the FDA and our research partners to validate the use of Haystack MRD in a variety of solid tumors, building on this first designation for early-stage [CRC],” Dan Edelstein, vice president and general manager of Haystack Oncology, said in the news release.¹ “Our goal is to deliver highly accurate, personalized monitoring of treatment response and recurrence to more patients, both in clinical care and in pharmaceutical trials, and this breakthrough designation brings us closer to our goal.”

The Haystack MRD test was engineered as a liquid biopsy test to identify low levels of ctDNA. According to researchers, ctDNA MRD testing may help reveal molecular evidence of disease recurrence months before it can be identified through imaging or other conventional screening methods. Developers noted that earlier detection may enable a deployment of proactive surveillance strategies as well as early intervention before clinically evident disease progression.

Additionally, in a survey conducted by The Harris Poll on behalf of the developers, a vast majority of oncologists (96%) reported that MRD testing has the potential to identify recurrence earlier than traditional screening methods, and approximately 50% suggested that imaging tests not detecting recurrence soon enough is among the primary reasons for why cancer recurrence is missed.⁴

According to developers, the Haystack MRD test is now available for clinical use and for clinical trials as an investigational device.

“Cancer liquid biopsy has the potential to revolutionize cancer diagnosis, treatment monitoring, and the detection of MRD soon after therapy—helping to better personalize patient care,” Dan Faden, MD, FACS, head and neck surgical oncologist and scientist at Massachusetts Eye and Ear, and a leading expert in head and neck cancer liquid-biopsy research, said in a news release.² “Given its promise, studying liquid biopsy in clinical contexts such as MRD is a major focus of our laboratories and clinical services.”

References

1. FDA grants breakthrough device designation for Haystack MRD circulating tumor DNA test from Quest Diagnostics. News release. Quest Diagnostics. August 25, 2025. Accessed August 26, 2025. https://tinyurl.com/5n8tnytx
2. Mass General Brigham launches two clinical trials to study Haystack MRD ctDNA as guide for post-surgical treatment for two cancer types. News release. Quest Diagnostics. August 7, 2025. Accessed August 26, 2025. https://tinyurl.com/yc42xd74
3. Allan Z, Sloane HS, Harper K, et al. Circulating tumor DNA (cDNA) analysis for improved treatment response assessment and prediction of clinical outcomes in patients with esophageal cancer. J Clin Oncol. 2025;43(suppl 16):4077. doi:10.1200/JCO.2025.43.16_suppl.4077
4. Oncologists report seeing more advanced cancers and say current tests are not catching cancer recurrence early enough, new Quest Diagnostics report finds. News release. May 13, 2025. Accessed August 26, 2025. https://tinyurl.com/9f2bxvn9