University Clinic Carl Gustav Carus, Urology, Dresden, Germany.
Tampere University Hospital and University of Tampere, Urology, Tampere, Finland.
Eur Urol. 2015 Mar;67(3):482-91. doi: 10.1016/j.eururo.2014.02.014. Epub 2014 Feb 20.
Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo.
To investigate ZA for the prevention of BMs in high-risk localised PCa.
DESIGN, SETTING, AND PARTICIPANTS: Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≥20 ng/ml, node-positive disease, or Gleason score 8-10.
Standard PCa therapy alone or combined with 4mg ZA intravenously every 3 mo for ≤4 yr.
BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups.
A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4±0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p=0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n=1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p=0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients.
ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr.
Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr.
The ZEUS trial is registered in the Dutch trial register www.trialregister.nl and the ISRCTN register at http://www.controlled-trials.com/ISRCTN66626762.
患有高危局限性前列腺癌（PCa）的患者有发生骨转移（BMs）的风险。唑来膦酸（ZA）可显著降低去势抵抗性转移性 PCa 患者的骨骼并发症发生率，与安慰剂相比。
研究 ZA 在高危局限性 PCa 中的作用。
设计、地点和参与者：一项随机、开放标签的多国研究，纳入至少具有以下一项特征的患者：前列腺特异性抗原（PSA）≥20ng/ml、淋巴结阳性疾病或 Gleason 评分 8-10。
单独接受标准 PCa 治疗或联合静脉注射 4mg ZA 每 3 个月一次，最长 4 年。
使用局部评估的骨成像程序（BIPs）评估 BMs，随后进行盲法中心审查。比较治疗组之间的 BMs、BMs 时间、总生存期和不良事件。
共有 1433 名随机患者中的 1393 名按意向治疗（ITT）进行了疗效分析，在 4±0.5 年时，1040 名患者有 BIP-BM 结果。在 ZA 组中，当地泌尿科医生/放射科医生诊断出 88 名 515 名患者（17.1%）的 BIP-BMs，在对照组中诊断出 89 名 525 名患者（17.0%）（卡方检验：p=0.95），两组之间的比例差异为 0.1%（95%置信区间[CI]，-4.4 至 4.7）有利于对照组。在 ITT 人群（n=1393）中，中位随访 4.8 年后，ZA 组的 BMs 估计比例为 14.7%，对照组为 13.2%（对数秩检验：p=0.65）。骨扫描的低热点被确认为转移灶，需要额外的影像学检查。仅对部分患者进行了 BIP 的中心审查。
在 4 年时，每 3 个月给予 ZA 被证明对高危局限性 PCa 患者的 BMs 预防无效。
在 4 年时，每 3 个月给予 ZA 被证明对高危非转移性 PCa 患者的骨转移预防无效。
ZEUS 试验在荷兰试验注册中心 www.trialregister.nl 和 ISRCTN 登记处进行登记，网址为 http://www.controlled-trials.com/ISRCTN66626762。
