Background Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was carried out based on aggregate data (AD) from all available studies. Methods Overall survival (OS) and failure-free survival data from completed Systemic Treatment Options for Cancer of the Prostate reviews of Doc, ZA and AAP and from recent trials of ZA and Cel contributed to this comprehensive AD-NMA. The primary outcome was OS. Correlations between treatment comparisons within one multi-arm, multi-stage trial were estimated from control-arm event counts. Network consistency and a common heterogeneity variance were assumed. Results We identified 10 completed trials which had closed to recruitment, and one trial in which recruitment was ongoing, as eligible for inclusion. Results are based on six trials including 6204 men (97% of men randomised in all completed trials). Network estimates of effects on OS were consistent with reported comparisons with ADT alone for AAP [hazard ration (HR) = 0.61, 95% confidence interval (CI) 0.53-0.71], Doc (HR = 0.77, 95% CI 0.68-0.87), ZA + Cel (HR = 0.78, 95% CI 0.62-0.97), ZA + Doc (HR = 0.79, 95% CI 0.66-0.94), Cel (HR = 0.94 95% CI 0.75-1.17) and ZA (HR = 0.90 95% CI 0.79-1.03). The effect of ZA + Cel is consistent with the additive effects of the individual treatments. Results suggest that AAP has the highest probability of being the most effective treatment both for OS (94% probability) and failure-free survival (100% probability). Doc was the second-best treatment of OS (35% probability). Conclusions Uniquely, we have included all available results and appropriately accounted for inclusion of multi-arm, multi-stage trials in this AD-NMA. Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer. AAP appears to be the most effective treatment, but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials. To fully account for patient variability across trials, changes in prognosis or treatment effects over time and the potential impact of treatment on progression, a network meta-analysis based on individual participant data is in development.

中文翻译：

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对于患有转移性、激素初治前列腺癌的男性来说，最佳的全身治疗是什么？STOPCAP 系统评价和网络荟萃分析。

背景 我们之前的前列腺癌系统治疗选择系统评价显示，当醋酸阿比特龙加泼尼松龙/泼尼松 (AAP) 或多西紫杉醇 (Doc)，而不是唑来膦酸 (ZA) 治疗时，患有转移性激素初治前列腺癌的男性患者的生存率有所提高。添加到雄激素剥夺疗法（ADT）中。试验证据还表明，将塞来昔布 (Cel) 与 ZA 和 ADT 联合使用具有益处。为了确定最佳治疗方法，根据所有可用研究的汇总数据 (AD) 进行了网络荟萃分析 (NMA)。方法 Doc、ZA 和 AAP 已完成的《前列腺癌全身治疗方案》综述以及最近的 ZA 和 Cel 试验中的总生存期 (OS) 和无失败生存数据为本次综合性 AD-NMA 做出了贡献。主要结局是 OS。一项多组、多阶段试验中治疗比较之间的相关性是根据对照组事件计数来估计的。假设网络一致性和共同的异质性方差。结果 我们确定了 10 项已结束招募的已完成试验和一项正在进行招募的试验，符合纳入条件。结果基于 6 项试验，包括 6204 名男性（所有已完成的试验中 97% 的男性被随机分配）。对 OS 影响的网络估计与报告的 AAP 与单独 ADT 的比较一致 [风险比 (HR) = 0.61，95% 置信区间 (CI) 0.53-0.71]，Doc（HR = 0.77，95% CI 0.68-0.87） 、ZA + Cel（HR = 0.78，95% CI 0.62-0.97）、ZA + Doc（HR = 0.79，95% CI 0.66-0.94）、Cel（HR = 0.94 95% CI 0.75-1.17）和 ZA（HR = 0.90 95% CI 0.79-1.03）。ZA+Cel的效果与各个治疗的相加效果一致。结果表明，AAP 最有可能成为 OS（94% 概率）和无失败生存（100% 概率）最有效的治疗方法。Doc 是第二好的 OS 治疗方法（概率为 35%）。结论 独特的是，我们在本次 AD-NMA 中纳入了所有可用的结果，并适当考虑了多组、多阶段试验的纳入。我们的结果支持 AAP 或 Doc 与 ADT 一起用于患有转移性激素初治前列腺癌的男性。AAP 似乎是最有效的治疗方法，但尚不清楚其程度如何以及这是否是由于 AAP 真正增加的益处或各个试验的不同特征所致。为了充分考虑试验中患者的变异性、预后或治疗效果随时间的变化以及治疗对进展的潜在影响，基于个体参与者数据的网络荟萃分析正在开发中。