ctDNA Blood Test Could Help Guide Radiotherapy in Patients with Limited Metastases

Clinicians often count metastatic lesions on X-ray, computed tomography (CT), or magnetic resonance imaging (MRI) to stratify patients, but this approach may not identify who benefits most from radiotherapy. Circulating tumor DNA (ctDNA) in blood offers a noninvasive measure of tumor activity. New findings demonstrate that a ctDNA blood test may help guide treatment selection and monitoring in oligometastatic cancer.

Researchers at The University of Texas MD Anderson Cancer Center (Houston, TX, USA) led the phase II randomized EXTEND Trial to evaluate whether a circulating tumor DNA blood test could help guide treatment in patients with oligometastatic solid tumors. The trial, presented at the European Society for Radiotherapy and Oncology (ESTRO) 2026 Congress and published in the Journal of Clinical Oncology, randomly assigned participants to receive standard drug therapy alone or drug therapy combined with radiation therapy. Blood samples were collected at baseline, three months, and disease progression to measure ctDNA levels.

The study enrolled 237 patients divided into six groups: pancreatic, breast, and kidney cancers; two prostate cancer cohorts with different hormone therapy schedules; and a basket of other malignancies. All participants had one to five metastases, reflecting the current imaging-based definition of early metastatic spread. The primary endpoint tested whether adding radiation therapy improved cancer control versus drugs alone, which was confirmed, while ctDNA was assessed as a treatment-guiding biomarker.

Patients with detectable ctDNA at baseline were more likely to experience continued tumor growth and death. Clearance of ctDNA occurred more often when radiation therapy to sites of spread was added to systemic treatment. Patients whose ctDNA cleared showed better outcomes and survival than those without clearance, while persistent or recurrent ctDNA after therapy suggested more aggressive disease, insufficient treatment effect, or tumor not visible on imaging.

Investigators indicated that ctDNA testing may help identify candidates for radiotherapy and refine management by signaling when a cancer has changed or developed resistance. The work was presented by an investigator from The Mayo Clinic, and expert commentary from ESTRO emphasized ctDNA as a noninvasive marker that could complement imaging. The Journal of Clinical Oncology publication represents the primary analysis across all tumor-histology baskets of the EXTEND Trial.

“More and more research is showing that treating patients with a limited spread of cancer with both drug therapy and high-precision radiotherapy can improve their chances of survival. This study—one of the largest carried out in this patient group—suggests that by adding a blood test we can also monitor and target patients' radiotherapy treatment much more effectively,” said Professor Matthias Guckenberger, ESTRO President, University Hospital Zurich, Switzerland.

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