Zoledronic Acid Improves Clinical Outcomes in Patients with Bone Metastatic Hormone-naive Prostate Cancer in a Multicenter Clinical Trial

Aim: To assess whether zoledronic acid (ZOL) adds to the effect of combined androgen blockade (CAB) in patients with hormone-naive bone metastatic prostate cancer. Patients and Methods: Patients were treated with either a combination of CAB (luteinizing hormone-releasing hormone agonist and bicalutamide) and ZOL (CAB-Z group) or CAB-alone (historical control patients, CAB-C group). ZOL was injected intravenously at 4 mg every 4 weeks. One hundred and five and 100 patients among 205 enrolled patients were assigned to the CAB-Z group and CAB-C group, respectively. The time to prostate-specific antigen (PSA) failure in patients in the CAB-Z group was compared to that in the CAB-C group. The primary end-point of the study was the time-to-PSA failure. Results: PSA and serum N-telopeptide of type I collagen (NTx) levels were examined before treatment and every 3 months after treatment. PSA failure occurred in 42 (40.0%) patients in the CAB-Z group and 48 (48.0%) patients in the CAB-C group. The biochemical recurrence-free rate was significantly lower in patients in the CAB-C group (p=0.004, by log-rank test). The categorical biopsy Gleason score pre-treatment serum NTx and treatment with ZOL were shown to be independent predictors of PSA failure-free survival time (p=0.040, p=0.005 and p=0.026, respectively). Conclusion: ZOL given with CAB as initial treatment delays the time-to-PSA failure in patients with hormone-naive bone metastatic prostate cancer.