Presented during the session “The oligo-(r)evolution: Long-term evidence and biological frontiers” at ESTRO 2026, new findings from the phase II randomized EXTEND trial suggest that circulating tumour DNA (ctDNA) may help identify which patients with oligometastatic cancer are most likely to benefit from metastasis-directed radiotherapy. The study was simultaneously published in the Journal of Clinical Oncology.
The findings come from one of the largest prospective studies evaluating ctDNA as a biomarker in oligometastatic disease.
𝗕𝗮𝗰𝗸𝗴𝗿𝗼𝘂𝗻𝗱
Oligometastatic cancer describes a disease state in which cancer has spread beyond the primary site but remains limited in number and location. Traditionally, this condition has been defined radiologically by counting visible metastatic lesions on CT, MRI, or PET imaging.
Over the past decade, multiple studies have shown that combining systemic therapy with local treatments such as stereotactic radiotherapy may improve disease control and survival in selected patients with oligometastatic disease. However, identifying which patients derive the greatest benefit from metastasis-directed therapy remains a major clinical challenge.
Researchers from The University of Texas MD Anderson Cancer Center and Mayo Clinic investigated whether ctDNA could provide a more biologically relevant way to characterize metastatic disease beyond conventional imaging alone.
𝗢𝗯𝗷𝗲𝗰𝘁𝗶𝘃𝗲
The study aimed to determine whether circulating tumour DNA could predict outcomes in oligometastatic cancer, identify patients most likely to benefit from radiotherapy, and monitor response to treatment over time.
Investigators also explored whether changes in ctDNA levels after treatment correlated with progression-free survival and overall survival.
𝗠𝗲𝘁𝗵𝗼𝗱𝘀
The EXTEND trial enrolled 237 patients across six disease-specific cohorts, including pancreatic, breast, kidney, and prostate cancers, as well as other solid tumours. Eligible patients had between one and five metastatic lesions.
Participants were randomized to receive either standard systemic therapy alone or systemic therapy combined with metastasis-directed radiotherapy delivered to sites of disease. Blood samples were collected at baseline, after three months of treatment, and again at disease progression. Researchers then analyzed samples for circulating tumour DNA.
𝗥𝗲𝘀𝘂𝗹𝘁𝘀
The primary endpoint of the EXTEND trial previously demonstrated improved cancer control with the addition of metastasis-directed radiotherapy. In the current biomarker analysis, investigators found that patients with detectable ctDNA at baseline experienced significantly worse outcomes.
Patients with persistent ctDNA were more likely to develop progressive disease and had inferior survival outcomes compared with patients whose ctDNA became undetectable during treatment.
Importantly, the addition of radiotherapy was associated with improved ctDNA clearance. Patients whose ctDNA cleared following treatment achieved substantially better long-term outcomes and survival, supporting the concept that ctDNA may serve as a dynamic marker of treatment response.
Researchers also noted that detectable ctDNA after therapy may indicate occult disease not visible on imaging, treatment resistance, or more aggressive tumour biology.
𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗜𝗺𝗽𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻𝘀
The findings suggest that ctDNA testing could complement conventional imaging when evaluating oligometastatic disease and may help clinicians refine decisions regarding radiotherapy intensification or systemic therapy adaptation.
The study also reinforces the expanding role of precision radiotherapy in metastatic cancer management, particularly in patients with limited metastatic burden.
According to the investigators, future studies may explore whether treatment strategies should be modified in patients with persistent ctDNA after therapy and whether ctDNA can help distinguish responding lesions from resistant disease sites.
𝗘𝘅𝗽𝗲𝗿𝘁 𝗣𝗲𝗿𝘀𝗽𝗲𝗰𝘁𝗶𝘃𝗲
Commenting on the study, Matthias Guckenberger, President of European Society for Radiotherapy and Oncology, noted that the integration of ctDNA testing with imaging techniques may offer a more refined approach for selecting and monitoring patients undergoing radiotherapy for oligometastatic disease.
Read full press release here.