Kaur Harmanpreet, Siemens D Robert, Black Angela, Robb Sylvia, Barr Spencer, Graham Charles H, Othman Maha
Department of Biomedical and Molecular Sciences, Queen's University.
Department of Urology, Kingston General Hospital.
Can Urol Assoc J. 2017 Jan-Feb;11(1-2):33-38. doi: 10.5489/cuaj.3936.
Androgen-deprivation therapy (ADT) is the mainstay of systemic therapy for advanced prostate cancer (PCa), but has significant adverse effects, including increasing concern for cardiovascular (CV) and thromboembolic (TE) complications. This study carefully investigates any relationship between ADT use and hypercoagulability as a possible mechanism of these adverse effects.
We performed a prospective, longitudinal study in a cohort of patients with advanced PCa initiating ADT (n=18). Controls included men with biochemical failure after local therapy on watchful waiting (n=10), as well as healthy controls (n=8). Global hemostasis was evaluated using the sensitive global hemostasis assay, thromboelastography (TEG). Patients were evaluated at baseline and every three months for a minimum of 12 months.
The results of the TEG studies demonstrated 14/18 (78%) of advanced PCa patients had evidence of a hypercoagulable state before initiating therapy. Significant baseline hypercoagulability was documented in this cohort compared to the two control groups. ADT did not appear to exacerbate hypercoagulability over time as a whole: only 10/18 (56%) patients had TEG findings consistent with hypercoagulability at the end of study. However, 3/18 17% PCa patients initiating ADT had significantly new hypercoagulable TEG changes on treatment compared to baseline.
This prospective pilot study demonstrates a complex interaction between ADT and hypercoagulable state in men with advanced PCa. TEG abnormalities were mostly associated with volume of cancer as compared to ADT use; however, it is possible that ADT may lead to hypercoagulability in a subset of men, suggesting that sensitive monitoring of coagulation of men on ADT could help identify those at risk of developing CV/TE complications. Study limitations include the relatively small cohort of men followed after initiating ADT and these results require confirmation in a larger trial to rule out subtle effects on hypercoagulability.
雄激素剥夺疗法（ADT）是晚期前列腺癌（PCa）全身治疗的主要方法，但具有显著的不良反应，包括对心血管（CV）和血栓栓塞（TE）并发症的日益关注。本研究仔细调查了ADT的使用与高凝状态之间的关系，将其作为这些不良反应的一种可能机制。
我们对一组开始接受ADT的晚期PCa患者（n = 18）进行了一项前瞻性纵向研究。对照组包括接受局部治疗后生化指标失败且进行观察等待的男性（n = 10）以及健康对照组（n = 8）。使用敏感的整体止血检测方法血栓弹力图（TEG）评估整体止血情况。在基线时以及之后每三个月对患者进行评估，至少持续12个月。
TEG研究结果显示，14/18（78%）的晚期PCa患者在开始治疗前有高凝状态的证据。与两个对照组相比，该队列中有显著的基线高凝状态。总体而言，ADT似乎并未随时间加剧高凝状态：在研究结束时，只有10/18（56%）的患者TEG结果与高凝状态一致。然而，3/18（17%）开始接受ADT的PCa患者在治疗期间与基线相比有显著的新的高凝TEG变化。
这项前瞻性试点研究表明，晚期PCa男性患者中ADT与高凝状态之间存在复杂的相互作用。与使用ADT相比，TEG异常大多与癌症体积相关；然而，ADT可能会导致一部分男性出现高凝状态，这表明对接受ADT治疗的男性进行凝血的敏感监测有助于识别那些有发生CV/TE并发症风险的人。研究局限性包括开始接受ADT后随访的男性队列相对较小，这些结果需要在更大规模的试验中得到证实，以排除对高凝状态的细微影响。
