ctDNA Improves Treatment Monitoring for Patients Receiving Metastasis-Directed Therapy

Analysis from one of the largest studies of its kind showed that circulating tumor DNA (ctDNA) testing provided new insights that could better guide treatment decisions compared to the current method of counting lesions for patients with early metastatic cancers, according to researchers from The University of Texas MD Anderson Cancer Center.

The findings were presented in a proffered paper session at the Congress of the European Society for Radiotherapy and Oncology (ESTRO 2026) and published in the Journal of Clinical Oncology.

The Phase 2 EXTEND trial, led by Chad Tang, M.D., associate professor of Genitourinary Radiation Oncology, previously demonstrated that metastasis-directed therapy (MDT) – most commonly radiation therapy – can improve outcomes for patients with oligometastatic cancers when combined with standard-of-care anti-cancer drug therapy. These findings have helped MDT become more widely adopted as a standard treatment for patients with oligometastatic prostate cancer.

As part of that research, Alex Sherry started an investigation while he was a resident at UT MD Anderson into whether ctDNA testing could improve on the current method of counting lesions on medical scans to determine which patients are most likely to benefit. Sherry, now at Mayo Clinic, presented the findings today. 

“While counting the lesions has its benefits, it is not as precise or reproducible as measuring ctDNA,” Tang said. “A non-invasive test for ctDNA levels was able to give us much more information about which patients were likely to benefit from MDT and whether that MDT was working during the course of treatment.”

Why does ctDNA appear to be a better indicator of response? 

In this study, blood was collected at the start of the trial and again at three months to be tested for ctDNA. Even with just these two data points, ctDNA testing was able to provide insights that counting lesions could not. 

The researchers found that tumors with detectable ctDNA at the start of the trial were more likely to progress, and that tumors treated with MDT had lower ctDNA levels. Additionally, they found that, if ctDNA was present after treatment, it could be a sign of a more aggressive cancer, that treatment was not effective, or that the cancer may have spread to sites not detected on the scans. 

“This is really valuable information that we did not have before,” Tang said. “Now that we know this kind of information is accurate and available, it not only has the potential to help guide treatment plans but also to help physicians react to changes during the course of treatment more quickly. It also adds to our growing body of knowledge of how MDT can change the course of disease for many patients.”

Reference: Sherry AD, Haymaker C, Wang S, et al. Addition of metastasis-directed therapy to standard of care for oligometastatic solid tumors: primary analysis of all tumor-histology baskets of the phase II randomized EXTEND trial. J Clin Oncol. 2026:10.1200/JCO-25-02856. doi: 10.1200/JCO-25-02856

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