A prospective interim clinical study evaluated a strategy combining enzalutamide (an androgen-receptor signaling inhibitor), denosumab, local radiotherapy (LRT) to the prostate, and metastasis-directed therapy (MDT) for men with poly-metastatic prostate cancer (≥4 bone metastases).

Twenty patients were enrolled, with an 18-month median follow-up. One-year progression-free survival (PFS) was 84.4%, radiographic PFS was 100%, and 85% achieved ≥90% reduction in PSA levels. Half of the cohort maintained PSA <0.2 ng/mL, a strong surrogate for improved overall survival.

Enzalutamide was specifically favored for its tolerability, while denosumab was added for its proven effect in delaying skeletal events in bone-metastatic prostate cancer. LRT offers both local control and the prevention of severe genitourinary complications. Despite a single-arm design, this combination matched or outperformed historical controls from the ARCHES, ENZAMET, and PEACE-1 trials where lower metastatic burdens were often enrolled.

The study demonstrates feasibility and safety of using aggressive multi-modal therapy in poly-metastatic prostate cancer, supporting the trend toward more comprehensive, upfront approaches in high-volume disease. Ongoing research is needed to confirm these findings and define patient selection

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