Randomized trial finds targeting individual metastases in oligometastatic breast cancer does not improve survival

UT MD Anderson Research News October 07, 2026

• Oligometastatic cancer has spread beyond the original tumor to a limited number of sites
• Study tested whether treating all visible breast cancer metastases with radiation or surgery improved outcomes beyond standard drug therapy
• In patients with four or fewer metastases, treating each visible metastatic tumor did not improve progression-free or overall survival
• Early results from blood tests that look for tumor cells did show promise and may help doctors identify patients most likely to benefit from this treatment in future studies

Treating individual metastatic tumors with highly focused radiation or surgery did not improve progression-free or overall survival for patients with oligometastatic breast cancer receiving first-line systemic therapy, according to results from the randomized NRG-BR002 clinical trial led by researchers at The University of Texas MD Anderson Cancer Center. 

The study, led by Steven Chmura, M.D., Ph.D., chair of Breast Radiation Oncology, was published today in the Journal of Clinical Oncology. The findings provide important evidence against routinely adding metastasis-directed treatment for patients with a limited number of breast cancer metastases when effective systemic therapy is already controlling the disease.

Oligometastatic cancer refers to metastatic disease that has spread beyond the original tumor but remains confined to a small number of sites. Advances in stereotactic body radiation therapy (SBRT) and surgery have made it possible to eradicate individual metastases, which raises the following question: Could treating every visible site of disease delay progression or extend survival? Researchers designed this trial to directly test that approach in breast cancer.

“There has been tremendous interest in whether aggressively treating every visible metastatic site could change the natural history of breast cancer for patients with only a few metastases,” Chmura said. “This randomized trial gives us important evidence that, for most patients in this setting, adding local treatment to effective systemic therapy does not improve progression-free or overall survival.”

Why doesn’t treating every visible metastasis improve outcomes in patients with oligometastatic breast cancer?
Although radiation or surgery can control individual metastases, the trial found that treating all visible metastases did not prevent new metastases from developing elsewhere. This suggests that eliminating visible tumors alone may not be enough to change the overall course of metastatic breast cancer. 

The Phase 2/3 NRG-BR002 trial enrolled 129 patients at 47 institutions across the United States and Canada, with 125 patients eligible for analysis. Participants had four or fewer metastatic lesions and were randomly assigned to receive either first-line systemic therapy alone or systemic therapy plus treatment of all known metastatic sites with SBRT or surgery.

The study did not meet its primary endpoint. Median progression-free survival was 23 months with systemic therapy alone compared with 19.5 months with metastasis-directed ablation, and overall survival also did not differ significantly between the groups. Because the trial did not show the required improvement in progression-free survival, it did not proceed to Phase 3.

Longer follow-up reinforced the findings, showing no significant improvement in progression-free survival and no evidence that ablation reduced the development of new metastases. 

Should radiation or surgery be added routinely to systemic therapy?
Based on these results, the researchers concluded that metastasis-directed SBRT or surgery should not be added routinely to first-line systemic therapy for oligometastatic breast cancer outside of clinical trials. Local treatment still has an important role when needed to relieve symptoms, such as pain or other problems caused by an individual metastatic lesion.

“More treatment is not always better treatment. These findings can help patients and physicians have clearer conversations about the expected benefit of additional radiation or surgery and potentially spare patients from treatments that add time, cost and potential side effects without improving survival,” Chmura said.

Could some patients still benefit from metastasis-directed treatment?
An exploratory analysis led by Wendy A. Woodward, M.D., Ph.D., professor of Breast Radiation Oncology, found that patients with no or very low levels of tumor cells circulating in their blood before treatment were more likely to benefit from targeted treatment of oligometastases. These patients went longer without their cancer getting worse, while patients with higher levels of circulating tumor cells did not see the same benefit.

The findings suggest that simply counting the number of places breast cancer has spread may not be enough to determine who should receive this aggressive treatment. In the future, blood-based markers such as circulating tumor cells and circulating tumor DNA could help doctors better identify which patients are most likely to benefit. Chelain Goodman, M.D., Ph.D., assistant professor of Breast Radiation Oncology, is leading the next generation of clinical trials incorporating this approach.

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This study was supported by the National Cancer Institute of the National Institutes of Health, the Ludwig Foundation for Cancer Research,  and the Breast Cancer Research Foundation. A full list of collaborating authors and their disclosures can be found with the full paper in the Journal of Clinical Oncology.