Metastasis-directed therapy significantly improved progression-free survival, radiologic progression–free survival, and castration resistance–free survival in patients with oligometastatic prostate cancer, according to a new study published by Tang et al 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 therapy to standard-of-care treatment.
According to corresponding author Chad Tang, MD, Associate Professor of Genitourinary Radiation Oncology at The University of Texas MD Anderson Cancer Center, gathering level 1 evidence of the benefits of metastasis-directed therapy in this cancer type has been a challenge due to several factors. Most significant among them is that only a small number of patients have oligometastatic cancer—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,” Dr. Tang said. “By bringing together all available patient data from randomized clinical trials, we have provided the best evidence to date that [metastasis-directed therapy] improves patient outcomes.”
What Is Metastasis-Directed Therapy?
Broadly, metastasis-directed therapy can include multiple treatment approaches. In this setting, the most common form of metastasis-directed therapy 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 disease progression and limiting the need for more aggressive therapies that will further impact quality of life.
The most common form of metastasis-directed therapy is stereotactic body radiation therapy. In previous studies, like the phase II EXTEND trial in patients with oligometastatic pancreatic cancer, metastasis-directed therapy significantly improved progression-free survival. These and similar findings have led to widespread adoption of metastasis-directed therapy 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. Individual patient data from seven trials were ultimately included in this meta-analysis, known as WOLVERINE.
Key Findings
The final analysis, which included 574 men, showed a significant benefit for the patients receiving metastasis-directed therapy in terms of progression-free, radiologic progression–free, and castration resistance–free survival.
Patients in the metastasis-directed therapy 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-resistant 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 5 toxicities were observed in either arm and any adverse effects above grade 2 were similar between the two arms.
“We hope that this data set will lay the groundwork for future phase III trials, which hopefully will show an overall survival benefit for these patients,” Dr. Tang said. “However, what this data does already show is the best evidence to date that [metastasis-directed therapy] significantly benefits patients without adding any notable safety risks.”
Initial data from this analysis were shared at the 2025 ASCO Genitourinary Cancers Symposium (Abstract 15). Along with the EXTEND trial, the studies used in this meta-analysis included the STOMP trial from Ghent University Hospital in Belgium; the ORIOLE trial led by Johns Hopkins; the SABR-COMET trial led by the London Health Sciences Centre in Canada; the ARTO trial from the University of Florence in Italy; and the RADIOSA trial from the European Institute of Oncology, IRCCS, in Milan, Italy.
DISCLOSURE: This trial was supported by the National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
