Largest Lung Cancer MRD Study Demonstrates Signatera™’s Strong Prognostic Value
Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) and precision medicine, has announced new clinical data presented at the IASLC 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea. The company and its research collaborators presented four abstracts at the meeting, including two oral presentations, highlighting the potential role of circulating tumor DNA (ctDNA) and molecular residual disease (MRD) testing in the management of patients with non-small cell lung cancer (NSCLC).
Among the presentations was a mini-oral session featuring what Natera described as the largest molecular residual disease dataset presented to date in lung cancer. The analysis included 1,129 patients with resected stage 1-3 NSCLC and covered an observation period extending from 2016 through 2025.
The study evaluated Signatera, Natera’s personalized, tumor-informed ctDNA test, for detection of molecular residual disease following surgery and during subsequent surveillance. The findings indicated that Signatera MRD status during the early post-surgical period was strongly associated with recurrence-free survival (RFS). The analysis also found that patients who tested positive for MRD during surveillance had a substantially higher risk of recurrence or death compared with patients who remained MRD-negative.
According to Natera, the results were consistent across both primary surgical and perioperative patient cohorts, supporting the potential applicability of Signatera monitoring across patients with resected stage 1-3 NSCLC.
Large-Scale Analysis Examines MRD After Lung Cancer Surgery
The study presented at WCLC included 1,129 patients who had undergone surgery for stage 1-3 NSCLC. Researchers evaluated Signatera MRD detection at different points following treatment, including an early post-surgical window defined as 7 to 90 days after surgery, as well as during ongoing surveillance.
Molecular residual disease refers to cancer cells or tumor-derived genetic material that may remain in the body after treatment but is not detectable through conventional imaging or clinical assessment. Detecting MRD through circulating tumor DNA can potentially provide information about a patient’s risk of recurrence before disease becomes visible through standard monitoring methods.
For patients with early-stage lung cancer, determining who remains at high risk of recurrence after surgery is an important clinical challenge. Although surgery can remove visible disease, some patients may have microscopic residual disease that subsequently contributes to relapse. Identifying these patients could provide additional information for treatment planning and follow-up.
In the Natera analysis, early post-surgical Signatera status showed a strong association with subsequent recurrence-free survival.
Signatera-Negative Patients Demonstrated Higher Three-Year RFS
One of the key findings was the difference in three-year recurrence-free survival between patients who were Signatera-negative and those who were Signatera-positive during the early post-surgical period.
According to the presented data, Signatera-negative patients had a 25% higher absolute three-year recurrence-free survival compared with patients who had detectable MRD in the early post-surgical window.
The findings suggest that a negative Signatera result during this period was associated with a more favorable recurrence profile, while detection of molecular residual disease identified patients with a higher likelihood of subsequent disease recurrence.
The analysis also evaluated MRD status over the surveillance period rather than relying solely on a single post-surgical measurement. This longitudinal approach is relevant because a patient’s molecular disease status can change over time, potentially providing additional information about recurrence risk during follow-up.
Natera reported that Signatera-positive patients had approximately five times the risk of recurrence or death during surveillance compared with patients who were MRD-negative.
The company said the consistency of the findings across different patient groups supports the potential role of serial MRD monitoring in resected stage 1-3 NSCLC.
Findings Could Inform Adjuvant Treatment Decisions
Adjuvant treatment decisions represent an important consideration following surgery for early-stage lung cancer. Clinicians must balance the potential benefits of additional systemic treatment against treatment-related risks and the likelihood that an individual patient will experience recurrence.
Traditional clinical and pathological factors provide important information for determining recurrence risk, but the study investigators highlighted the challenge of identifying which patients have residual disease following surgery.
Charu Aggarwal, M.D., MPH, FASCO, the Leslye Heisler Professor for Lung Cancer Excellence at the University of Pennsylvania’s Perelman School of Medicine and principal investigator of the study, said determining which patients remain at risk of recurrence is one of the challenges in early-stage lung cancer.
Aggarwal noted that the analysis included more than 1,100 patients and showed that Signatera MRD status, both shortly after surgery and during surveillance, was associated with recurrence-free and overall survival outcomes.
The findings may contribute to ongoing research into how MRD information could be incorporated into treatment decision-making. However, prognostic information does not automatically establish that using an MRD test to guide treatment improves patient outcomes. Prospective clinical studies evaluating MRD-guided treatment strategies remain important for determining how such testing should be incorporated into routine care.
Data Consistent Across Surgical Cohorts
Another notable aspect of the analysis was the consistency of the findings across both primary surgical and perioperative cohorts.
The primary surgical cohort and perioperative cohort represent different treatment settings within resected NSCLC. Consistent associations between Signatera MRD status and outcomes across these groups could support broader investigation of ctDNA monitoring in patients who undergo surgery as part of their lung cancer treatment.
The ability to detect molecular signals after treatment may offer clinicians an additional layer of information alongside pathology, imaging, clinical characteristics, and other established risk factors.
Natera’s findings presented at WCLC add to the company’s broader body of work evaluating the use of personalized ctDNA testing in oncology. Signatera is designed as a tumor-informed assay, meaning the test is developed using information from an individual patient’s tumor to identify cancer-associated DNA fragments in blood.
Four Natera-Related Presentations at WCLC 2026
Natera and its collaborators presented four abstracts at the 2026 World Conference on Lung Cancer, covering different applications of ctDNA, MRD, and molecular biomarkers in NSCLC.
The presentations included:
Abstract P2.192
Presenter: Deborah Doroshow, M.D., Ph.D.
Title: ctDNA After Definitive Therapy ± Immunotherapy and Association with Survival Outcomes in Locally Advanced Unresectable NSCLC
This poster presentation examined the relationship between circulating tumor DNA following definitive therapy, with or without immunotherapy, and survival outcomes in patients with locally advanced unresectable NSCLC.
The study reflects the growing interest in using ctDNA as a biomarker to assess residual disease and potentially provide information about outcomes following treatment.
Abstract P2.200
Presenter: Seohee Shim, M.D.
Title: ctDNA-based Molecular Residual Disease as a Predictive Biomarker for Treatment Stratification in Unresectable Stage 3 NSCLC
This presentation focused on the potential use of ctDNA-based MRD as a predictive biomarker for treatment stratification in patients with unresectable stage 3 NSCLC.
Biomarker-driven treatment strategies are being investigated as a way to identify differences in disease risk and potentially tailor treatment approaches according to molecular characteristics.
Abstract MO05.07
Presenter: David Gandara, M.D.
Title: KRAS G12C Predicts Superior Outcomes with 1L Cemiplimab for Non-Squamous aNSCLC With PD-L1 ≥ 50%: Data From EMPOWER-Lung 1
This mini-oral presentation examined outcomes associated with KRAS G12C in patients with nonsquamous advanced NSCLC and PD-L1 expression of at least 50%, using data from the EMPOWER-Lung 1 study.
The presentation highlights the continued investigation of molecular characteristics and biomarkers in advanced lung cancer and their potential relationship with treatment outcomes.
Abstract MO11.09
Presenter: Charu Aggarwal, M.D., MPH, FASCO
Title: Post-Surgical Molecular Residual Disease Detection, Adjuvant Treatment Patterns, and Overall Survival in Resected Stage 1-3 NSCLC
This mini-oral presentation contained the large-scale analysis of post-surgical MRD detection, adjuvant treatment patterns, and overall survival among patients with resected stage 1-3 NSCLC.
The dataset included 1,129 patients and examined Signatera status during both the early post-surgical period and subsequent surveillance.
Growing Role of Precision Medicine in Lung Cancer
The data presented by Natera at WCLC 2026 illustrate the expanding role of precision medicine and molecular monitoring in lung cancer research. While imaging and conventional clinical assessments remain central to patient management, blood-based biomarkers such as ctDNA are being investigated for their ability to identify molecular signals that may provide additional information about residual disease.
For early-stage NSCLC, this information could be particularly relevant following definitive treatment. Patients who appear disease-free based on conventional assessments can have substantially different underlying risks of recurrence. MRD testing may provide an additional method for identifying these differences.
The large size of the Natera analysis, combined with its extended observation period and evaluation of MRD both shortly after surgery and during surveillance, provides further clinical evidence regarding the association between Signatera status and patient outcomes.
At the same time, the presented findings primarily demonstrate the prognostic association between MRD detection and outcomes. Further prospective evidence will be important to determine how MRD testing can be incorporated into treatment pathways and whether MRD-guided interventions can improve clinical outcomes.
For Natera, the WCLC presentations reinforce the company’s focus on applying cell-free DNA technology and precision medicine to cancer care. The company’s continued research in NSCLC is aimed at understanding how molecular information can complement existing clinical tools and potentially support more individualized approaches to monitoring and treatment.
The 2026 WCLC data therefore provide additional evidence supporting investigation of Signatera MRD monitoring in resected stage 1-3 NSCLC while contributing to the broader scientific effort to understand the role of ctDNA in lung cancer management.
About Natera
Natera is a global leader in cell-free DNA and precision medicine, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are supported by more than 400 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California, and through Foresight Diagnostics, its subsidiary, operates an ISO 27001-certified and CAP-accredited laboratory certified under CLIA in Boulder, Colorado. For more information, visit www.natera.com.