WOLVERINE Study Shows The Benefits of Metastases Directed Therapy

The WOLVERINE study is a major analysis combining patient data from seven phase 2 trials, published in The Lancet Oncology. It looked at 574 men with oligometastatic prostate cancer (meaning up to five spots of cancer spread), mostly to bones or lymph nodes. Six of those trials (472 men) directly compared adding metastasis-directed therapy (MDT) to standard care (SOC) versus SOC alone. Median follow-up was about 41 months.

SOC was usually hormone therapy like ADT, sometimes with stronger drugs called ARPIs (Darolutamide, Enzalutamide, Apalutamide and similar). MDT meant targeted radiation (mostly SABR) or surgery to hit all visible cancer spots. Trials included STOMP, ORIOLE, and others. The main goals were to check progression-free survival (PFS) and overall survival (OS). They also tracked time to new scans showing growth (rPFS) and time before the cancer stops responding to hormone therapy (CRFS).

MDT plus SOC worked much better for delaying progression. PFS risk dropped by more than half: trial HR 0.44 (p<0.0001), patient HR 0.45 (p<0.0001). Median PFS went from 21 months with SOC to 35 months with MDT—a 14-month gain. rPFS improved too: trial HR 0.60 (p=0.0039), patient HR 0.59 (p<0.0001). CRFS got better: trial HR 0.58 (p=0.019), patient HR 0.58 (p=0.017), pushing median time to hormone resistance from 63 to 72 months.

These wins held up across groups, like new metastases versus ones that came back later, or hormone-sensitive versus resistant cancer. Even when SOC included ARPIs, MDT added extra delay. For OS, results trended positive but missed full proof: trial HR 0.63 (p=0.051), patient HR 0.64 (p=0.057). (Note about OS: take into account the heterogeneity of ages, fitness levels, and comorbidities in the study population.)
Four-year survival was 87% with MDT versus 75% without.

Side effects stayed low, like in the original trials, serious radiation issues in just 5-10% of cases, no big jump in other problems.

WOLVERINE delivers high-reliability level 1a evidence as a systematic review with individual patient data meta-analysis of seven phase 2 RCTs (low Cochrane RoB 2.0 risk), offering robust pooled outcomes superior to summary-statistic analyses.

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