(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA was host to a case-based session addressing the evolving landscape of the management of oligometastatic disease. Dr. Chad Tang presented WOLVERINE, an analysis from the X-MET collaboration leveraging individual patient data (IDT) from randomized trials of metastasis-directed therapy (MDT) in oligometastatic prostate cancer (omPC).
Although more prospective randomized data exists for oligometastatic prostate cancer, data investigating MDT is limited to several smaller phase II trials. Much has been hypothesized regarding patient subgroups who do or do not benefit from MDT, but subgroup analyses are limited. Current phase Il randomized trials have spanned several eras in metastatic prostate cancer imaging and treatment.
The goal of the X-MET collaboration was to amalgamate all randomized data investigating oligometastatic solid tumors. The study investigators identified all published trials randomizing oligometastatic(<5 metastases) prostate cancer patients to MDT and standard of care (SOC) versus SOC alone. Individual patient data was pooled, and the following endpoints harmonized across studies:
- Progression free survival (PFS)
- Radiographic PFS (rPFS)
- Castration resistance-free survival (CRFS)
- Overall survival (OS)
Two parallel analyses were conducted (banked in PROSPERO: CRD 4203479078):
- Meta-analysis using common and random effect models to calculate pooled hazard ratios
- Cox regression utilizing individual patients stratified by trial enrollment
This collaboration includes 5 trials of 472 oligometastatic prostate cancer patients followed for a median of 41 months. These patients are randomized 1:1 to MDT + SOC (n=248) or SOC alone (n=224). The baseline patient characteristics are summarized below:
With regards to progression-free survival, the most highly powered outcome in the majority of these trials, the addition of MDT was associated with significant improvements irrespective of whether analysis was performed at the trial level (HR: 0.44, 95% CI: 0.35-0.57) or using Cox regression, stratified by trial (32 months versus 14.9 months; HR: 0.45, 95% CI: 0.35–0.58, p<0.001).
Subgroup analysis by castration status (i.e., resistant versus sensitive) demonstrated that MDT maintained a consistent PFS benefit. Further subgroup analyses by receipt of primary treatment (yes vs no), cancer stage (N1 + M1a vs M1b/c), number of metastases (1–2 vs 3–5), and receipt of ADT in CSPC setting (yes vs no) all demonstrated consistent PFS benefits for MDT with HRs of 0.4–0.5.
Radiographic PFS similarly favored the MDT group (median 35 versus 21 months; HR: 0.59, 95% CI: 0.46–0.76, p<0.001):
Analysis of freedom from castration resistance in the castration sensitive subset only (n=257) demonstrated that MDT improved median time to castration resistance by 9 months (72 versus 63 months; HR: 0.58, p=0.02):
For overall survival, the addition of MDT to standard of care improved 48 months overall survival by 12% (87% versus 75%, HR 0.64, 95% CI: 0.40–1.01, p=0.057):
A summary table of the pooled outcomes is shown below:
Dr. Tang concluded as follows:
- Pooled analysis of all published trials randomizing oligometastatic prostate cancer patients to systemic therapy +/- MDT demonstrated improvements in PFS, rPFS, and castration resistance-free survival.
- MDT improved overall survival with a p-value of 0.051 in the random effects model.
- An MDT benefit was maintained across subgroups including patients with untreated primaries, staging imaging, castration sensitive/resistance status, and treatment with/without ADT.
Presented by: Chad Tang, MD, Associate Professor, Radiation Oncology, MD Anderson Cancer Center, Houston, TX
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
Related content: Metastasis-Directed Therapy Improves Outcomes in Oligometastatic Prostate Cancer in WOLVERINE Study - Chad Tang