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WOLVERINE meta-analysis: MDT linked to progression benefits, not survival gain, in oligometastatic prostate cancer

An individual patient meta-analysis found that although overall survival did not meet significance criteria, MDT plus SOC was associated with benefits across several progression-related endpoints versus SOC.

  • Chad Tang, MD; Alex D Sherry, MD; Hyunsoo Hwang, PhD; David P Farris, MSIS; Giulio Francolini, MD; Vanessa Di Cataldo, MD; et al.

  • February 1, 2026

  • The Lancet Oncology
  • The Lancet Oncology, Volume 27, Issue 2, Pages 181–190
  • 10.1016/S1470-2045(25)00658-8

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Evidence before this study

Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is becoming widely used for the treatment of oligometastatic prostate cancer. Available evidence is limited to phase 2 randomised trials showing benefit from MDT plus standard of care (SOC) compared with SOC for the signal-finding endpoints (eg, progression-free survival). However, there is little evidence of improvement in later endpoints, such as radiographic progression-free survival, castration resistance-free survival, and overall survival. We conducted a systematic review to identify all randomised trials investigating MDT for patients with oligometastatic prostate cancer from Embase, PubMed, CENTRAL, MEDLINE, and databases. Our search included trials evaluating multiple tumour types. General search terms were (oligometa* OR oligo-metasta* OR oligorecurrent) AND cancer AND (surgery OR radiation OR ablation) AND (randomized controlled trial OR controlled clinical trial). This systematic review was conducted from database creation to Nov 3, 2023, and updated on May 4, 2025. Seven randomised trials enrolling men with oligometastatic prostate cancer were identified, of which six randomised patients to MDT plus SOC versus SOC. Two additional trials, RAVENS (which randomised to MDT versus MDT plus Radium 223) and PEACE-V STORM (which randomised men with only lymph node oligometastases to MDT versus MDT plus elective local therapy to the uninvolved lymph nodal chain) were published after our systematic review.

Added value of this study

Our individual patient meta-analysis included seven trials randomising patients with oligometastatic prostate cancer. Six trials comparing MDT plus SOC versus SOC were included in the primary and secondary analysis examining the efficacy of MDT. To the best of our knowledge, WOLVERINE represents the first individual patient meta-analysis using more than two trials, showing that MDT was significantly associated with benefit in progression-free survival, radiographic progression-free survival, and castration resistance-free survival. The association between MDT and overall survival did not meet significance criteria. The benefit of MDT was consistent throughout most studies and in relevant patient and treatment subgroups.

Implications of all the available evidence

To the best of our knowledge, WOLVERINE includes all available clinical trials randomising men with oligometastatic prostate cancer to MDT plus SOC versus SOC during our search window. Our findings offer the highest-level evidence to date supporting the use of MDT in men with oligometastatic prostate cancer. Exploratory subgroup analyses offered additional insights into the value of MDT within relevant patient and treatment subgroups.

Source: The Lancet Oncology

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