MDT Boosts Survival Outcomes in Oligometastatic Prostate Cancer

Adding metastatic-directed therapy (MDT) to standard of care (SOC) improved progression-free survival (PFS), radiological PFS, and castration resistance-free survival in patients with oligometastatic prostate cancer, according to a meta-analysis of 7 phase 2 studies conducted by investigators from The University of Texas MD Anderson Cancer Center, in Houston, Texas, and published in Lancet Oncology. The most common form of MDT is stereotactic body radiation therapy.

A total of 472 patients from 6 trials were randomly assigned to receive MDT plus SOC (n = 248) vs SOC alone (n = 224) with a median follow-up time of 40.7 months.

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 with patients receiving standard of care alone. These findings were consistent across the individual trials and in the aggregated data.

MDT was associated with improved progression-free survival in all trials individually and across trials in aggregate (HR, 0.44; 95% CI, 0.35-0.56; P <. 0001). MDT was associated with improvement in radiographic PFS for 2 trials individually and across all trials in aggregate (HR,0.60; 95% CI, 0.42-0.85; P = .0039).

Patient Characteristics

Regarding patient characteristics, groups were well balanced, with both groups exhibiting a median PSA of 1.9 ng/mL (SOC group IQR,0.5-6.6; MDT plus SOC group IQR, 0.6-4.5). Patients in the SOC group were slightly older and more received a second-generation androgen receptor pathway inhibitor.

Investigators reported that 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 2 arms.

“We hope that this dataset will lay the groundwork for future phase 3 trials, which hopefully will show an overall survival benefit for these patients,” lead author Chad Tang, MD, an associate professor of genitourinary radiation oncology at The University of Texas MD Anderson Cancer Center, said in a release. “However, what these data show are the best evidence to date that MDT significantly benefits patients without adding any notable safety risks.”

Meta-Analysis

Databases searched were ClinicalTrials.gov, MEDLINE, CENTRAL, PubMed, and Embase from database creation to Nov 3, 2023, and was updated on May 4, 2025. An additional manual search of ClincialTrials.gov and relevant oncology conferences was conducted. These data were analyzed in the WOLVERINE meta-analysis, which investigated the benefit of MDT plus SOC versus SOC. This meta-analysis is registered with PROSPERO (CRD42023479078).

The prespecified coprimary end points were progression-free survival (PFS) and overall survival (OS); prespecified secondary endpoints were radiographic progression-free survival (rPFS) and castration resistance-free survival. WOLVERINE included 7 studies, 6 of which randomly assigned patients with oligometastatic prostate cancer to MDT plus SOC or SOC alone and were included in the primary and secondary efficacy analyses

This meta-analysis provides the strongest evidence to date that MDT improves PFS, radiographic PFS, and castration resistance-free survival, findings that were consistent across individual studies and most patient and treatment subgroups. The authors concluded that the association between MDT and overall survival warrants further investigation due to a relative lack of events for this end point.

REFERENCE

Tang C, Sherry AD, Hwang H, et al. Metastasis-directed therapy and standard of care versus standard of care for oligometastatic prostate cancer (WOLVERINE): a systematic review and individual patient data meta-analysis from the X-MET collaboration. Lancet Oncol. 2026;27:181–190. doi:10.1016/S1470-2045(25)00658-8