MDT associated with prolonged PFS in oligometastatic prostate cancer

Findings from the WOLVERINE meta-analysis have been published in Lancet Oncology, showing that adding metastasis-directed therapy (MDT) to standard-of-care (SOC) is linked with improvements in progression-free survival (PFS), radiographic progression-free survival (rPFS), and castration resistance-free survival among men with oligometastatic prostate cancer.¹

The publication of WOLVERINE represents the first analysis from the X-MET collaboration, a global consortium of data from randomized trials in oligometastatic cancers. The investigators of the current study tapped into the collaboration in an effort to address the paucity of level 1 evidence supporting MDT in oligometastatic cancers, which can be a difficult disease state to study due to its low prevalence and relative indolence, according to lead author Chad Tang, MD.²

“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,” explained Tang, who is a radiation oncologist at MD Anderson Cancer Center in Houston, Texas, in a news release on the results.² “By bringing together all available patient data from randomized clinical trials, we have provided the best evidence to date that MDT improves patient outcomes.”

In total, the analysis included individual patient data from 574 men across 7 phase 2 trials. The primary analysis was conducted in 6 of these studies, where patients were randomly assigned to receive MDT plus SOC (n = 248) vs SOC alone (n = 224). The co-primary end points were PFS and overall survival (OS). Secondary end points included rPFS and castration resistance-free survival.

The median follow-up across the studies was 40.7 months (IQR, 25.6 to 53.7). Overall, the addition of MDT to SOC was associated with an improvement in PFS in both the trial-level analyses (trial-level HR, 0.44; 95% CI 0.35 to 0.56; P < .0001) and the patient-level analyses (patient-level HR, 0.45; 95% CI, 0.35 to 0.57; P < .0001). Specifically, MDT plus SOC was associated with a median 7.6-month extension in PFS compared with SOC alone. 

Further, the addition of MDT was also associated with a benefit in rPFS (trial-level HR, 0.60; 95% CI, 0.42 to 0.85; P = .0039; patient-level HR, 0.59; 95% CI, 0.46 to 0.76; P < .0001) and castration resistance-free survival (trial-level HR, 0.58; 95% CI, 0.37 to 0.92, P = .019; patient-level HR, 0.58; 95% CI, 0.37 to 0.91; P = .017). Those in the MDT arms demonstrated a median improvement of 4.9 months before radiographic disease progression and 2.5 months before castration-resistant disease compared with those receiving SOC alone.

The investigators also noted a trend toward improved OS with MDT, although the association did not achieve statistical significance (trial-level HR, 0.63; 95% CI, 0.39 to 1.00; P = .051; patient-level HR, 0.64; 95% CI, 0.40 to 1.01; P = .057).

There was no significant difference in safety between the 2 arms. The safety profiles were similar for any AEs above grade 2, and no grade 5 toxicities were reported in either arm.

According to the authors, further work is needed.

“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 concluded in the news release.² “However, what this data does already show is the best evidence to date that MDT significantly benefits patients without adding any notable safety risks.”

REFERENCES

1. 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(2):181-190. doi:10.1016/S1470-2045(25)00658-8

2. Study shows strong evidence for effectiveness of metastasis-directed radiation therapy in prostate cancer. News release. University of Texas M.D. Anderson Cancer Center. February 2, 2026. Accessed February 12, 2026. https://www.eurekalert.org/news-releases/1115038