This Test Helped Identify Treatment in Colorectal Cancer Surgery

Patients with stage 3 colorectal cancer who tested positive for minimal residual disease (MRD) using Signatera after surgery experienced a meaningful survival advantage when Celebrex (celecoxib) was added to standard chemotherapy compared with Signatera-negative patients, who derived no significant benefit, according to findings from the phase 3 CALGB (Alliance)/SWOG 80702 study, which were shared in JAMA Oncology.

The phase 3 trial is a large, randomized study evaluating the predictive value of circulating tumor DNA (ctDNA) testing in patients who underwent surgery for stage 3 disease. According to the data, which were also shared in a press release from Natera, Inc., patients who were Signatera-positive after surgery saw approximately a 40% reduction in the risk of death when Celebrex was added to FOLFOX chemotherapy compared with chemotherapy plus placebo. Patients who were Signatera-negative, however, did not appear to benefit from adding the drug.

Disease-free survival reached 41.0% at three years in the Celebrex group compared with 22.6% in the placebo group, and overall survival was improved as well. At five years, 61.6% of Signatera-positive patients who received Celebrex remained alive, compared with 39.9% in the placebo group.

“For patients with detectable ctDNA after surgery, adding Celebrex to standard chemotherapy improved both DFS and OS,” Dr. Jonathan Nowak, of Brigham and Women’s Hospital and corresponding author of the research, stated in the news release. “In addition to highlighting Signatera’s predictive abilities in this setting, the publication also underscores its value as a prognostic marker for disease recurrence and survival.”

The publication builds on results initially presented during the 2025 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.

Study Overview and Patient Population

The analysis included 940 patients with available plasma samples following surgery. All were randomized to receive standard FOLFOX chemotherapy, with or without Celebrex. Investigators then evaluated whether Signatera MRD status predicted who would benefit from Celebrex treatment, a non-steroidal anti-inflammatory drug.

MRD is a small number of cancer cells left in the body after treatment, according to the University of Texas MD Anderson Cancer Center website. These cells have the potential to come back and cause relapse in patients.

Signatera is designed to detect small amounts of tumor-specific DNA (ctDNA) remaining in the bloodstream after treatment, which can signal residual cancer that is not visible on scans. In this study, the test separated patients into two groups: Signatera-positive patients who still showed detectable ctDNA after surgery, and Signatera-negative patients who did not.

Importantly, investigators found that the benefit of Celebrex in Signatera-positive patients appeared consistent regardless of demographic or clinical factors analyzed. Celebrex improved disease-free survival for Signatera-positive patients with both PIK3CA wild-type tumors and PIK3CA-altered tumors.

Study authors reported no significant risk reduction in recurrence or death for patients who were Signatera-negative after surgery, regardless of PIK3CA status. According to the report, this pattern underscores the importance of identifying MRD, since the presence or absence of detectable ctDNA appeared to guide treatment benefit.

Additional Analysis Strengthened Treatment Signal

Further analysis evaluated patients whose samples met minimum quality-control criteria for Signatera testing in Natera’s certified laboratory environment.

Approximately 66% of plasma and DNA samples fell into this category for this study. Natera noted that in standard laboratory practice, approximately 99% of samples meet these quality standards, meaning that real-world results may closely reflect this subset analysis.

Understanding Key Patient Takeaways

These findings suggest that MRD testing using Signatera may help identify a population of patients who could benefit from adding Celebrex to conventional chemotherapy, although the benefit is limited to those who remained MRD-positive after surgery.

“This publication marks another important milestone in colorectal cancer research, highlighting Signatera as a critical tool in disease management,” Dr. Adham Jurdi, senior medical director of gastrointestinal oncology at Natera, concluded in the news release. “It further demonstrates Signatera’s predictive utility in identifying, with great precision, patients with MRD who will likely benefit from Celebrex in addition to chemotherapy, regardless of their PIK3CA status.”

References

1. Natera Announces Publication of Signatera™ Analysis from Randomized, Phase III CALGB (Alliance)/SWOG 80702 Study in Colorectal Cancer, by Natera, Inc. News release; Dec. 18, 2025.
2. “What is minimal residual disease (MRD),” by Clayton Boldt. The University of Texas MD Anderson Cancer Center; July 15, 2020.

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