Department of Urology, University of Washington School of Medicine, 3515 E. Spring St, Seattle, WA 98122.
Urol Oncol. 2020 Dec;38(12):912-917. doi: 10.1016/j.urolonc.2020.07.004. Epub 2020 Sep 6.
Androgen deprivation therapy (ADT), a mainstay of therapy for advanced prostate cancer (CaP), may raise patients' risk of cardiovascular disease (CVD) and related adverse events. The new androgen receptor (AR)-targeted agents are associated with hypertension and cardiovascular events. The most common non-CaP cause of death in men with CaP is CVD. The purpose of this review is to raise awareness of the metabolic and CV risks of ADT and to encourage proper monitoring of patients treated with hormonal agents.
To review the cardiovascular and metabolic risk profiles of hormonal agents in managing patients with advanced CaP, the author searched PubMed, meeting abstracts, and clinicaltrials.gov from 1941 through early 2020 using search terms such as locally advanced CaP guidelines, gonadotropin-releasing hormone (GnRH) agonist/antagonist, ADT, CaP, CVD, abdominal obesity metabolic syndrome, and cerebrovascular disorder. The author ultimately selected 42 of the most relevant publications for inclusion in this paper.
Data regarding cardiovascular risk in patients with CaP on ADT are inconsistent, though there may be evidence of less risk in GnRH antagonists than GnRH agonists in men with pre-existing CVD. Observational post hoc studies generally show higher risks for GnRH agonists than GnRH antagonists. A review of 6 phase 3 trials found that patients treated with GnRH antagonists had lower cardiovascular risk than those treated with agonists during the first year of ADT, and these differences were especially significant among men with pre-existing CVD. Additionally, a small prospective randomized phase 2 study, as well as a large phase 3 trial, showed that there were significantly more major adverse cardiovascular events in patients treated with a GnRH agonist compared to a GnRH antagonist. In addition, the AR-targeted agents in conjunction with ADT have been shown to have more hypertension and/or cardiovascular risk than ADT plus placebo in numerous phase 3 trials.
Whether there is a difference in CVD risk between GnRH agonists and antagonists is the subject of an ongoing phase 3 trial with cardiovascular endpoints. Addition of newer AR-targeted agents may confer additional risk over ADT alone. Clinicians treating advanced CaP should be aware of underlying comorbidities of their patients before choosing either conventional ADT or adding AR-targeted agents. Physicians should monitor patients for hypertension, diabetes, and cardiovascular side effects that may require intervention in order to minimize downstream adverse events and should communicate with other colleagues on the patient's health care team to ensure the best outcomes.
去势治疗（ADT）是治疗晚期前列腺癌（CaP）的主要方法，可能会增加患者患心血管疾病（CVD）和相关不良事件的风险。新型雄激素受体（AR）靶向药物与高血压和心血管事件相关。在患有 CaP 的男性中，非 CaP 最常见的死亡原因是 CVD。本综述的目的是提高对 ADT 的代谢和心血管风险的认识，并鼓励对接受激素治疗的患者进行适当监测。
为了回顾管理晚期 CaP 患者时激素药物的心血管和代谢风险概况，作者在 1941 年至 2020 年初使用了“局部晚期 CaP 指南”、“促性腺激素释放激素（GnRH）激动剂/拮抗剂”、“ADT”、“CaP”、“CVD”、“腹部肥胖代谢综合征”和“脑血管疾病”等搜索词，在 PubMed、会议摘要和 clinicaltrials.gov 上进行了搜索，并检索了相关出版物。作者最终选择了 42 篇最相关的出版物纳入本文。
关于 ADT 治疗的 CaP 患者的心血管风险的数据不一致，但对于已有 CVD 的男性，GnRH 拮抗剂的风险可能低于 GnRH 激动剂。观察性事后研究通常表明 GnRH 激动剂的风险高于 GnRH 拮抗剂。对 6 项 3 期试验的回顾发现，与 GnRH 激动剂治疗组相比，GnRH 拮抗剂治疗组在 ADT 的第一年心血管风险较低，在已有 CVD 的男性中，这些差异尤为显著。此外，一项小型前瞻性随机 2 期研究和一项大型 3 期试验表明，与 GnRH 拮抗剂相比，接受 GnRH 激动剂治疗的患者发生重大不良心血管事件的发生率显著更高。此外，在许多 3 期试验中，与 ADT 加安慰剂相比，AR 靶向药物联合 ADT 显示出更多的高血压和/或心血管风险。
GnRH 激动剂和拮抗剂在 CVD 风险方面是否存在差异是一项正在进行的 3 期临床试验的主题，该试验有心血管终点。添加新型 AR 靶向药物可能会在单独使用 ADT 的基础上增加额外的风险。治疗晚期 CaP 的临床医生在选择常规 ADT 或添加 AR 靶向药物之前，应了解患者的潜在合并症。医生应监测患者的高血压、糖尿病和心血管副作用，这些副作用可能需要干预，以尽量减少下游不良事件，并与患者医疗团队的其他同事沟通，以确保最佳结果。
