Molecular residual disease (MRD) testing has become one of the most transformative tools in precision oncology, reshaping how clinicians make treatment decisions across the cancer care continuum. By enabling detection of MRD, Signatera has proven to be an actionable assay to help inform escalation, de-escalation and personalization of cancer treatment.
Better Identifying Who to Treat
Treatment decisions after surgery or systemic therapy are generally driven by clinicopathologic features such as tumor stage, lymph node involvement, and imaging results. While these factors remain important, they are imperfect predictors of recurrence.
MRD testing allows clinicians to identify patients who are more likely to benefit from additional treatment. An MRD-positive result after surgery may justify therapy escalation or clinical trial enrollment, whereas negative patients may be spared unnecessary chemotherapy.
Using MRD Testing for Therapy De-Escalation
This concept of treatment de-escalation is especially important as oncology continues to balance efficacy with quality of life. Many cancer therapies carry substantial long-term consequences, both physiological and financial. MRD testing provides a potential pathway toward reducing overtreatment without compromising patient outcomes.
Treatment Response Monitoring
Traditional imaging may take months to reveal whether therapy is working. Serial MRD testing offers a dynamic view of molecular response, allowing clinicians to observe whether ctDNA levels are clearing or persisting over time. Persistent ctDNA levels may indicate resistance and prompt earlier intervention, while ctDNA clearance may provide reassurance of disease control.
Signatera Detect Cancer Recurrence Earlier Than Imaging
Because Signatera can detect cancer recurrence months before imaging, many clinicians are now choosing to treat patients at the time they become ctDNA positive even if they remain negative on imaging. This MRD-guided approach or Treat on MRD (TOMR) has been recently represented in the data and has spurred the development of MRD-guided trials.
MRD-Guided Trials
The promise of these MRD-guided clinical trials is to better stratify patients, enrich high-risk populations, and evaluate whether therapy modifications based on molecular response may improve outcomes. In this way, MRD testing is becoming integrated not only into patient care but also into the architecture of modern drug development.
Examples of MRD-Informed Clinical Studies
- Bladder Cancer (IMvigor011 trial): patients were only randomized for treatment if they were Signatera-positive and with no radiographic signs of disease.1
- Uterine cancer: Signatera identified 100% of uterine cancer recurrences in advance of imaging.2
- Breast cancer (EBLIS study): Signatera detected relapse up to 38 months earlier than imaging, with a median lead time of 10.5 months.3
- Anal squamous cell carcinoma: Signatera-positivity preceded clinical and/or radiographic recurrence in 100% of recurrent cases.
Precision Medicine and Personalized Care
MRD testing is increasingly being used as an actionable biomarker capable of informing treatment decisions, personalizing therapy intensity, and enabling earlier intervention. By transforming invisible molecular signals into actionable clinical insight, MRD testing is helping usher oncology into a new era of truly individualized care.
Natera is the exclusive partner of Yvonne Awards Ceremony and OncoDaily Reception
Disclaimer:
Signatera has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified. ©2026 Natera, Inc. All Rights Reserved.
References:
1. Powles T, Kann AG, Castellano D, et al. ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer N Engl J Med. 2025; 393:2395-2408
2. Peter W. Ketch et al.., Using Circulating Tumor DNA–Based Molecular Residual Disease Detection for Postoperative Monitoring in Early-Stage Uterine Cancer. JCO Precis Oncol 9, e2500286(2025). DOI:10.1200/PO-25-00286
3. Shaw JA, Page K, Wren E, et al. Serial postoperative circulating tumor DNA assessment has strong prognostic value during long-term follow-up in patients with breast cancer. JCO Precis Oncol. 2024; 8:e2300456
4. Romesser, P.B., Bercz, A., Alvarez, J. et al. Tumor-informed circulating tumor DNA stratifies recurrence risk and survival in anal squamous cell carcinoma. Nat Commun 17, 3241 (2026). https://doi.org/10.1038/s41467-026-69984-y