Test Summary
Haystack MRD®
Clinical use
- Detect residual cancer following curative-intent treatment
- Assess risk of cancer recurrence
- Monitor for treatment response
- Assist recurrence surveillance
Clinical background
Minimal residual disease (MRD) is characterized by a small number of tumor cells that cannot be detected by conventional techniques.1 Because these cells may lead to cancer recurrence, MRD is an important risk factor that can be assessed to help provide personalized care to patients with solid tumors. MRD can be identified by testing for circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA) that is released by tumor cells into the blood. Reliably detecting ctDNA has been challenging since it is present at very low levels in MRD-positive patients.1 Haystack MRD is an MRD test that can detect ultralow levels of ctDNA, enabling enhanced accuracy for identifying MRD.
Detection of ctDNA after curative-intent treatment is associated with a higher risk of recurrence 2–4 and can help guide patient care. For example, in the randomized controlled DYNAMIC trial, either MRD testing or standard risk assessment was performed to guide decisions on using postsurgical adjuvant chemotherapy for stage II colorectal cancer (CRC).5 Compared to those who received standard of care, chemotherapy was used in about 50% fewer patients who received MRD-guided care without compromising 2-year recurrence-free survival (RFS).5 After 5 years, RFS remained uncompromised among those in the MRD-guided group (88% RFS with MRD guidance and 87% with standard assessment).6 Haystack MRD is an advanced version of the technology used in the DYNAMIC trial.
ctDNA can also be used to monitor for treatment response. Persistence or increase of ctDNA levels during systemic therapy is associated with lower rates of treatment response and poorer survival outcomes. Conversely, clearance or decline of ctDNA levels during therapy is associated with higher rates of treatment response and improved outcomes.4,7,8
ctDNA allows for earlier detection of treatment response or cancer recurrence than conventional methods, which may help clinicians provide more timely care. For example, in a study using neoadjuvant immunotherapy for mismatch repair–deficient cancers, Haystack MRD detected clinical complete response earlier than imaging-based assessment; median time to ctDNA clearance was 1.4 months and median time to imaging-based response was 6.1 months.9 Furthermore, using an earlier version of Haystack MRD technology, ctDNA detected recurrence in patients with stage II CRC earlier than carcinoembryonic antigen (CEA), a standard surveillance biomarker; median lead time ahead of imaging-based recurrence was 167 days with ctDNA and 61 days with CEA.10
Haystack MRD is a tumor-informed MRD test that uses variants identified in a patient’s tumor to subsequently test for ctDNA in the blood. The test is available as 2 offerings for initial and follow-up testing:
- Haystack MRD Baseline (test code 13682) is required for initial testing and includes tumor tissue analysis, development of a personalized panel for tumor variants, and plasma testing for ctDNA.
- Haystack MRD Monitoring (test code 13151) is used for follow-up testing and includes plasma testing for ctDNA only. This test uses the patient’s personalized panel from prior baseline testing.
Individuals suitable for testing
- Individuals diagnosed with solid tumors who have undergone curative-intent treatment
- Individuals diagnosed with solid tumors who are receiving or have received neoadjuvant or adjuvant therapy
Methods
- Whole-exome sequencing of tumor tissue and a matched blood sample to identify up to 50 variants for a personalized multiplex PCR panel (included with Haystack MRD Baseline only)
- Isolation of cfDNA from plasma, library preparation, and enrichment for targeted regions using the personalized PCR panel
- Proprietary molecular barcoding performed during library preparation and enrichment to minimize sequencing errors
- Next-generation sequencing of enriched cfDNA followed by variant and MRD calling process
- Results reported: MRD detection status, mean ctDNA molecules/mL plasma, number of variants detected, test history
- Analytical sensitivity: 95% limit of detection at 0.0006% tumor fraction11
- Analytical specificity: 100% concordance between samples with and without interfering substances
Interpretive information
An "MRD Detected" result indicates detection of ctDNA and the presence of residual cancer. An "MRD Not Detected" result reflects lack of ctDNA detection at the time of blood draw, which may indicate the absence but does not exclude the possibility of residual cancer. Test history showing increases in mean ctDNA molecules/mL is associated with disease progression; test history showing decreases in mean ctDNA molecules/mL is associated with tumor response.
The level of detectable ctDNA can vary due to biological factors that are unrelated to tumor status. The results of this test should be interpreted in the context of tumor pathology, patient characteristics, standard risk features, radiography, and other laboratory data.
References
- Pantel K, Alix-Panabières C. Minimal residual disease as a target for liquid biopsy in patients with solid tumours. Nat Rev Clin Oncol. 2025;22(1):65-77. doi:10.1038/s41571-024-00967-y
- Mittal A, Valiente CM, Tamimi F, et al. Utility of ctDNA in predicting relapse in solid tumors after curative therapy: a meta-analysis. JNCI Cancer Spectr. 2023;7(4):pkad040. doi:10.1093/jncics/pkad040
- Christensen E, Birkenkamp-Demtröder K, Sethi H, et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J Clin Oncol. 2019;37(18):1547-1557. doi:10.1200/jco.18.02052
- Xia L, Pu Q, Kang R, et al. Dynamic ctDNA informs whole-course postoperative precise management of NSCLC (LUNGCA study). JNCI: J Natl Cancer Inst. 2025;117(7):1474-1484. doi:10.1093/jnci/djaf061
- Tie J, Cohen JD, Lahouel K, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261-2272. doi:10.1056/nejmoa2200075
- Tie J, Wang Y, Lo SN, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial. Nat Med. 2025;31(5):1509-1518. doi:10.1038/s41591-025-03579-w
- Al-Showbaki L, Wilson B, Tamimi F, et al. Changes in circulating tumor DNA and outcomes in solid tumors treated with immune checkpoint inhibitors: a systematic review. J Immunother Cancer. 2023;11(2):e005854. doi:10.1136/jitc-2022-005854
- Gouda MA, Huang HJ, Piha-Paul SA, et al. Longitudinal monitoring of circulating tumor DNA to predict treatment outcomes in advanced cancers. JCO Precis Oncol. 2022;6(6):e2100512. doi:10.1200/po.21.00512
- Cercek A, Foote MB, Rousseau B, et al. Nonoperative management of mismatch repair–deficient tumors. N Engl J Med. 2025;392(23):2297-2308. doi:10.1056/nejmoa2404512
- Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92. doi:10.1126/scitranslmed.aaf6219
- Prathapam R, Champion KJ, Blakely KE, et al. Analytical validation of the ultra-sensitive tumor-informed Haystack MRD assay for detection of ctDNA in solid tumor patients. Presented at: Association for Molecular Pathology 2024 Annual Meeting and Expo; November 19, 2024.
Content reviewed 10/2025
Colorectal Cancer: Laboratory Support of Diagnosis and Management
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
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