Study shows strong evidence for effectiveness of metastasis-directed radiation therapy in prostate cancer

Metastasis-directed therapy (MDT) significantly improved outcomes in patients with oligometastatic prostate cancer, according to a new study from researchers at The University of Texas MD Anderson Cancer Center published in The Lancet Oncology. The study is a first-of-its-kind meta-analysis of individual patients across all available randomized clinical trials evaluating the addition of metastasis-directed radiation therapy to standard-of-care treatment.

According to corresponding author Chad Tang, M.D., associate professor of Genitourinary Radiation Oncology, gathering level one evidence of the benefits of MDT in this cancer type has been a challenge due to several factors. Most significant among them are that only a small number of patients have oligometastatic cancer—meaning they have multiple metastases but not enough to be considered widely metastatic—and the relative indolence of oligometastatic disease.

“If we can identify and treat this disease in the narrow window before it spreads too far, we know that patient outcomes are significantly better. But gathering this data is difficult,” Tang said. “By bringing together all available patient data from randomized clinical trials, we have provided the best evidence to date that MDT improves patient outcomes.”

Broadly, MDT can include multiple treatment approaches. In this setting, the most common form of MDT is radiation therapy, which targets metastases at a stage when cancer has begun to spread but hasn’t yet spread widely. This approach potentially brings several benefits to patients, such as delaying the time to progression and limiting the need for more aggressive therapies that will further impact quality of life.

The most common form of MDT is stereotactic body radiation therapy (SBRT), a type of very precise radiation therapy. In previous studies, like the Phase II EXTEND trial presented in 2024, MDT significantly improved progression-free survival (PFS).

These and similar findings have led to widespread adoption of MDT in the oligometastatic setting, despite the lack of level one evidence.

To try and address that lack of data, researchers from several institutions created a global consortium, known as X-MET, to gather the data from all randomized trials for analysis at MD Anderson. Individual patient data from seven trials were ultimately included in this meta-analysis, known as WOLVERINE.

This study, which included 574 men, showed a significant benefit for the patients receiving the MDT arm in PFS, radiographic PFS, and castration resistance-free survival.

Patients in the MDT arm gained a median of 7.6 months before disease progression, 4.9 months before radiographic disease progression, and 2.5 months before developing castration-resistance disease, compared to patients receiving standard of care alone. These findings were consistent across the individual trials and in the aggregated data.

Additionally, there were no significant differences in safety between the treatment arms. No grade five toxicities were observed in either arm, and any adverse effects above grade two were similar between the two arms.

“We hope that this dataset will lay the groundwork for future Phase III trials, which hopefully will show an overall survival benefit for these patients,” Tang said. “However, what this data does already show is the best evidence to date that MDT significantly benefits patients without adding any notable safety risks.”