Signatera MRD Assay Displays High Sensitivity, Specificity in Sarcoma

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The personalized molecular residual disease (MRD) test Signatera demonstrated high levels of sensitivity and specificity in monitoring circulating tumor DNA (ctDNA) in patients with soft tissue and bone sarcomas, according to results from a retrospective, real-world study.1

During the study, more than 2100 plasma samples collected from approximately 200 patients with sarcomas. Outcomes from personalized ctDNA monitoring were assessed against radiographic imaging results, and patients were followed through treatment, progression, and surveillance.

Findings announced by Natera showed that Signatera displayed a recurrence sensitivity of 89% and a specificity of 100% in the overall population. For patients with leiomyosarcoma, the rates of sensitivity and specificity were 93% and 100%, respectively. In patients with leiomyosarcoma who experienced disease progression, the correlation rate between ctDNA kinetics and treatment response was 90%.

“[These] data represent a major step forward in understanding how ctDNA monitoring can be applied across a diverse range of sarcoma subtypes,” Beatrice J. Sun, MD, of department of surgery at Stanford University in California, stated in a news release. “With the ability to noninvasively detect disease recurrence and monitor treatment response, Signatera demonstrates the potential to meaningfully improve personalized care for patients with sarcoma.”

Based on the results of this retrospective study, Natera intends to facilitate a prospective trial to further assess the clinical utility and potential role of Signatera in driving treatment decision-making and disease monitoring for patients with sarcoma.

“This is the most comprehensive dataset to date on ctDNA monitoring in sarcoma, and it shows excellent performance of Signatera in a difficult-to-monitor cancer,” Alexey Aleshin, MD, corporate chief medical officer and general manager of oncology at Natera, added in a news release. “The heterogeneity of sarcoma demands a personalized approach, and these results support Signatera’s unique ability to track disease status with precision across a broad spectrum of subtypes.”

The Signatera assay, which is personalized for each patient, is an MRD test that utilizes ctDNA with the goal of detecting residual cancer in the body, identifying signs of recurrence, and driving treatment decisions.

In another study presented at the 2025 AACR Annual Meeting, findings showed that tumor-specific ctDNA findings were consistent with radiographic surveillance in patients with high-risk sarcomas.2

Data demonstrated that among evaluable patients (n = 16), the rates of sensitivity and specificity with the Signatera assay in detecting disease recurrence were 83.33% (95% CI, 35.88%-99.58%) and 90.00% (95% CI, 55.50%-99.7%), respectively. The positive predictive value and negative predictive value were 83.33% (95% CI, 42.94%-97.08%) and 90.00% (95% CI, 59.78%-98.20%), respectively.

The study included patients with metastatic (n = 3) and nonmetastatic (n = 13) high-risk sarcomas. At baseline, all patients had no evidence of disease and negative ctDNA status. Within 28 days of a negative ctDNA result, patients underwent another ctDNA draw and a radiographic scan, and this continued during each cycle in the absence of ctDNA positivity. Congruence between ctDNA and radiographic monitoring was based on whether ctDNA and radiographic scans both remained negative, or if ctDNA converted to positive within 21 days of radiographic recurrence.

Investigators highlighted findings for 2 patients who became ctDNA positive more than 2 weeks prior to a recurrence was detected on radiographic imaging. They also noted that ctDNA detection was delayed in a patient with osteosarcoma who experienced pulmonary progression, and they explained that further research is needed to elaborate on the ctDNA shedding patters of specific sarcoma subtypes.

“ctDNA may serve as a valuable surveillance tool alongside imaging in high-risk sarcoma management,” lead study author Chahat Rana, DS, of UT Southwestern Medical Center in Dallas, Texas, and colleagues wrote in a poster presentation of the data.

References

• Largest sarcoma study to date with ctDNA analysis demonstrates excellent performance for Signatera. News release. Natera. May 5, 2025. Accessed May 7, 2025. https://www.natera.com/company/news/largest-sarcoma-study-to-date-with-ctdna-analysis-demonstrates-excellent-performance-for-signatera/
• Rana C, Wang DY, Dann AM, Alex NA, Chandrasekaran S. Congruence of tumor-specific ctDNA and radiographic recurrence in high-risk sarcoma. Presented at: 2025 AACR Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract 3342/12.