Blood Test After Surgery May Predict Colon Cancer Recurrence Risk

For people diagnosed with stage 3 colon cancer, one of the most pressing questions after surgery is whether the cancer is truly gone, and whether additional treatment is necessary. New findings from the largest published study of molecular residual disease (MRD) testing suggest that a simple blood test may offer clearer answers than traditional staging alone, according to a news release from Guardant Health, Inc.

Data published in The Journal of Clinical Oncology show that a circulating tumor DNA (ctDNA) blood test, Guardant Reveal, more accurately identifies patients at high risk of cancer recurrence after surgery than standard methods used today. The study supports the routine use of ctDNA testing to guide treatment and monitoring decisions for patients with stage 3 colon cancer following surgery.

Researchers found that patients with detectable cancer DNA in their blood after surgery were significantly more likely to experience recurrence and had worse survival outcomes, even when traditional staging suggested a lower risk.

ctDNA blood test identifies patients at higher risk of colon cancer recurrence

The phase 3 study included more than 2,000 patients with stage 3 colon cancer who had undergone surgery and had blood samples collected before starting adjuvant chemotherapy. Approximately 20% of patients still had detectable ctDNA in their blood following surgery, indicating the presence of microscopic cancer cells that imaging and pathology tests could not detect.

Patients with detectable ctDNA faced a four- to six-fold higher risk of cancer recurrence or death compared with those whose blood tests were ctDNA-negative. Notably, even patients with smaller tumors or fewer affected lymph nodes — features typically associated with better outcomes — had more than a six-fold higher risk of recurrence if ctDNA was present.

Researchers also found that measuring the amount of ctDNA, known as tumor fraction, provided additional insight. Patients with higher tumor fractions were more likely to experience early recurrence and worse survival outcomes, suggesting that ctDNA levels may further refine risk assessment beyond a simple positive or negative result.

These findings highlight how ctDNA testing may help identify patients who could benefit from closer monitoring, alternative treatment strategies, or clinical trials.

Why traditional staging has limitations

Stage 3 colon cancer is typically defined by tumor size and whether cancer has spread to nearby lymph nodes. After surgery, many patients receive adjuvant chemotherapy to reduce the risk of recurrence. However, traditional staging does not always accurately predict which patients will benefit most from additional treatment.

Some patients with higher-stage features never experience recurrence, whereas others with seemingly favorable disease do. This uncertainty can lead to overtreatment for some patients and missed opportunities for earlier intervention in others.

Circulating tumor DNA testing offers a different approach by detecting fragments of cancer DNA shed into the bloodstream. The presence of ctDNA after surgery suggests that cancer cells remain in the body, even when scans appear clear. This concept, known as molecular residual disease, has emerged as a powerful predictor of outcomes across multiple cancer types.

How the study was conducted

The study was conducted by researchers from Mayo Clinic in collaboration with Guardant Health and the Alliance for Clinical Trials in Oncology. Blood samples were analyzed using the Guardant Reveal test, a tissue-free ctDNA assay designed to detect cancer DNA without requiring tumor tissue for comparison.

Researchers evaluated whether ctDNA detection after surgery was associated with recurrence risk and overall survival, comparing results with standard tumor-node-metastasis (TNM) staging. Outcomes were tracked over time to assess how well ctDNA predicted disease progression.

By enrolling more than 2,000 patients, the study represents the largest evaluation of ctDNA-based MRD testing in stage 3 colon cancer to date, strengthening confidence in the findings.

All participants had resected stage 3 colon cancer and provided blood samples after surgery but before starting chemotherapy. The large and diverse patient population allowed researchers to examine outcomes across a wide range of tumor sizes, lymph node involvement, and clinical risk profiles.

Importantly, ctDNA testing identified high-risk patients even among those traditionally considered lower risk based on pathology alone. This suggests that ctDNA testing could play a valuable role in personalizing postoperative care.

Additional findings and what this means for patients

Experts involved in the study emphasized that ctDNA testing may help answer one of the most common patient questions after surgery: Am I really cancer-free?

“The data suggest that not only the presence of ctDNA, but the amount of ctDNA, as identified by Guardant Reveal may help refine risk beyond standard TNM staging, and could be used to guide adjuvant treatment and surveillance decisions,” said Dr. Frank Sinicrope, professor of oncology and medicine at Mayo Clinic and principal investigator for the study. “ctDNA testing after surgery improves the accuracy of estimating a patient’s risk of cancer recurrence, enabling more tailored recommendations for adjuvant chemotherapy and follow-up monitoring. It also identifies high risk patients who are likely to recur despite standard treatment, and who may benefit from alternative therapeutic approaches.”

“This large study adds to growing evidence that ctDNA testing with Guardant Reveal after surgery helps answer the question patients care about most: Am I really cancer-free?” said Dr. Craig Eagle, Guardant Health chief medical officer. “Personalizing care after surgery is essential as clinicians and patients decide what comes next. Guardant Reveal fits easily into routine practice and provides timely, actionable insight—helping identify patients at high risk while sparing others unnecessary treatment and anxiety.”

For patients with stage 3 colon cancer, these findings suggest that a blood test after surgery may soon become an important tool for guiding what comes next — offering a more personalized and precise approach to care during a critical phase of survivorship.

References

1. “Largest Published Study of Molecular Residual Disease (MRD) in Stage III Colon Cancer Shows Guardant Reveal Blood Test More Precisely Identifies Risk of Recurrence After Surgery to Support Timely Treatment Decisions,” by Guardant Health, Inc. News release; Feb. 2, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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