The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Mechanical Engineering, National University of Singapore, Kent Ridge, Singapore.
Prostate Cancer Prostatic Dis. 2018 Nov;21(4):451-460. doi: 10.1038/s41391-018-0059-4. Epub 2018 Jul 9.
Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US Food and Drug Administration safety warning. This study aims to perform a systematic review and meta-analysis on previous studies to determine whether ADT is associated with TEs in men with PCa.
Medline, Embase, and Cochrane Library databases were searched for relevant studies. These studies comprised those that compared ADT versus control to treat PCa, reported TEs as outcome, and were published before January 2018. Multivariate adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) were calculated using random- or fixed-effects models.
Five retrospective population-based cohort studies involving 170,851 ADT users and 256,704 non-ADT users were identified. Deep venous thrombosis (DVT) was found significantly associated with gonadotropin-releasing hormone (GnRH) agonists alone (HR = 1.47, 95% CI: 1.07-2.03; P = 0.017; I = 96.3%), GnRH agonists plus oral antiandrogen (AA) (HR = 2.55, 95% CI: 2.21-2.94; P < 0.001; I = 0.0%), and AA alone (HR = 1.49, 95% CI: 1.13-1.96; P = 0.004; I = 0.0%), but not with orchiectomy (HR = 1.80, 95% CI: 0.93-3.47; P = 0.079; I = 94.8%). In addition, pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 2.26, 95% CI: 1.78-2.86; P < 0.001; I was unavailable) and orchiectomy (HR = 2.12, 95% CI: 1.44-3.11; P < 0.001; I = 57.2%). This relationship was also supported with subgroup analyses based on different continents and races.
GnRH agonists alone, GnRH plus AA, and AA alone cause excess DVT in men with PCa after controlling the demographic and disease characteristics and other confounding factors, although statistically significant difference was not observed in orchiectomy group. Additionally, GnRH agonists alone and orchiectomy can increase the incidence of PE.
雄激素剥夺疗法（ADT）是否会导致前列腺癌（PCa）男性发生过多的血栓栓塞事件（TE）仍存在争议，这也是美国食品和药物管理局发出安全警告的原因。本研究旨在对以往的研究进行系统回顾和荟萃分析，以确定 ADT 是否与 PCa 男性的 TEs 相关。
检索了 Medline、Embase 和 Cochrane 图书馆数据库，以寻找相关研究。这些研究包括比较 ADT 与对照组治疗 PCa、将 TEs 作为结局并在 2018 年 1 月之前发表的研究。使用随机或固定效应模型计算多变量调整后的风险比（HR）和相关 95%置信区间（CI）。
确定了 5 项回顾性基于人群的队列研究，涉及 170851 名 ADT 使用者和 256704 名非 ADT 使用者。发现促性腺激素释放激素（GnRH）激动剂单独使用时与深静脉血栓形成（DVT）显著相关（HR=1.47，95%CI：1.07-2.03；P=0.017；I=96.3%），GnRH 激动剂加口服抗雄激素（AA）（HR=2.55，95%CI：2.21-2.94；P<0.001；I=0.0%）和 AA 单独使用（HR=1.49，95%CI：1.13-1.96；P=0.004；I=0.0%），但与睾丸切除术（HR=1.80，95%CI：0.93-3.47；P=0.079；I=94.8%）无关。此外，GnRH 激动剂单独使用与肺栓塞（PE）显著相关（HR=2.26，95%CI：1.78-2.86；P<0.001；I 不可用）和睾丸切除术（HR=2.12，95%CI：1.44-3.11；P<0.001；I=57.2%）。这一关系也得到了基于不同大洲和种族的亚组分析的支持。
在控制人口统计学和疾病特征以及其他混杂因素后，GnRH 激动剂单独使用、GnRH 加 AA 和 AA 单独使用会导致 PCa 男性发生过多的 DVT，尽管在睾丸切除术组未观察到统计学上的显著差异。此外，GnRH 激动剂单独使用和睾丸切除术可增加 PE 的发生率。
