WOLVERINE findings highlight benefits of MDT in oligometastatic prostate cancer

Findings from WOLVERINE, a global meta-analysis of several randomized trials, suggest that metastasis-directed therapy (MDT) confers benefits in several survival-related outcomes in oligometastatic prostate cancer.¹

Chad Tang, MD, BS, MS

“Although there exists more prospective randomized data for oligometastatic prostate cancer, the data investigating metastasis-directed therapy is limited to generally several smaller phase 2 trials. Much has been hypothesized regarding patient subgroups who do or do not benefit from metastasis-directed therapy, but these analyses are limited. Finally, the current phase 2 randomized trials that do exist have spanned several eras in metastatic prostate cancer imaging and treatment. Thus, we sought to pool the existing data in the X-MET collaboration, which is meant to amalgamate all randomized investigating oligometastatic solid tumors,” explained Chad Tang, MD, BS, MS, associate professor of radiation oncology at the University of Texas MD Anderson Cancer Center in Houston, at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California.

Tang and his colleagues identified all published trials that randomly assigned patients with oligometastatic prostate cancer (fewer than 5 metastases) to MDT and standard of care (SOC) vs SOC alone. Individual patient data were pooled, with progression-free survival (PFS), radiographic PFS (rPFS), castration-resistance free survival (CRFS), and overall survival (OS) harmonized across studies. The investigators conducted 2 parallel analyses: a meta-analysis using common and random effect models to calculate pooled HRs and a Cox regression that incorporated individual patients who were stratified by trial enrollment.

Contributing studies included ARTO (NCT03449719), STOMP (NCT01558427), COMET (NCT01446744), EXTEND (intermittent and continuous cohorts, NCT03599765), and ORIOLE (NCT02680587). A total of 472 patients with oligometastatic prostate cancer were included. Median follow-up was 41 months. Patients were randomly assigned to MDT plus SOC (n = 248) or SOC alone (n = 224). A total of 125 (50%) patients in the MDT plus SOC group received a second-generation androgen receptor pathway inhibitor compared with 134 (60%) patients in the SOC alone group. Fifty-two (21%) patients in the MDT plus SOC group received androgen deprivation therapy alone compared with 40 (18%) in the SOC alone group. Median number of metastases was 2 for each group.

Regarding PFS, in the trial-level analysis, the HR was 0.44 (95% CI, 0.35-0.57; P < .0001). Median PFS was 35 months in the MDT plus SOC group vs 21 months in the SOC alone group. In the Cox regression analysis, the HR was 0.45 (95% CI, 0.35-0.58; P < .0001). For rPFS, the HR for trial-level analysis was 0.60 (95% CI, 0.43-0.85; P = .0039), the HR for the Cox regression analysis was 0.59 (95% CI, 0.46-0.76; P < .0001). For CRFS, the HR for the trial-level analysis was 0.58 (95% CI, 0.37-0.92; P = .019), and the HR for the Cox regression analysis was 0.58 (95% CI, 0.37-0.91; P = .020). Median CRFS was 72 months in the MDT plus SOC group vs 63 months in the SOC alone group. For OS, the HR for the trial-level analysis was 0.63 (95% CI, 0.39-1.004; P = .051), and the HR for the Cox regression analysis was 0.64 (95% CI, 0.40-1.01; P = .057). The 48-month OS was 87% in the MDT plus SOC group vs 75% in the group receiving SOC alone.

“In summary, across the different end points, the pooled analysis of all published trials randomizing oligometastatic prostate cancer to MDT vs not in addition to standard of care systemic therapy or observation reveal an improvement in [PFS] and later end points…MDT benefit was maintained across subgroups, including patients who had do novo presentations and thus untreated primaries, independent of the different staging modalities used across studies, independent of castration-sensitive and resistant status, and independent of whether the patient was treated with or without ADT,” Tang said.

REFERENCE

1. Tang C, Sherry AD, Hwang H, et al. World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): an analysis from the X-MET collaboration. J Clin Oncol 2025;43(suppl 5). Abstract 15. doi:10.1200/JCO.2025.43.5_suppl.15