Efficacy and Safety of Combination Androgen-Receptor Signaling Inhibitors, Denosumab, and Local Radiotherapy for Poly-Metastatic Prostate Cancer.

BACKGROUND: The Treatment of Metastatic Castration-Sensitive Prostate Cancer (mCSPC) has dramatically changed over the past decade. To improve oncological outcomes, pharmacological treatments have evolved to include two-or three-drug combinations, and the efficacy of local radiation therapy (LRT) at the prostate combined with denosumab chemotherapy has been discussed. AIMS: This study aimed to provide an interim evaluation of the combination of androgen receptor signaling inhibitors denosumab, LRT, and metastasis-directed therapy (MDT) for prostate cancer with multiple bone metastases (poly-PCa). METHODS: We are currently conducting a single-arm prospective study to evaluate the combination of enzalutamide, LRT, denosumab, and MDT in terms of improving oncological outcomes in patients with poly-PCa. The primary endpoints were prostate-specific antigen (PSA)-based progression-free survival (PFS) and radiographic PFS (rPFS). RESULTS: Twenty patients have been enrolled in the study to date. The median follow-up period thus far is 18.0 months (interquartile range, 14.0-25.8 months). The 1-year PFS rate is 84.4% at present, and the rPFS rate is 100%. Seventeen patients (85.0%) achieved a PSA reduction of ≥ 90% versus their baseline values at enrollment, and 10 (50.0%) maintained PSA levels of < 0.2 ng/mL. CONCLUSION: This treatment strategy is expected to improve the oncological outcomes of patients with poly-PCa. A more comprehensive report of this study with more patients and a longer observation period is forthcoming.