Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
JAMA Oncol. 2016 Apr;2(4):500-7. doi: 10.1001/jamaoncol.2015.4917.
Androgen-deprivation therapy (ADT) through surgical castration is equally effective as medical castration in controlling prostate cancer (PCa). However, the adverse effect profiles of both ADT groups have never been compared.
To provide a comparative effectiveness analysis of the adverse effects of gonadotropin-releasing hormone agonists (GnRHa) vs bilateral orchiectomy in a homogeneous population.
DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort of 3295 men with metastatic PCa between January 1995 and December 2009 66 years or older was selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database.
Orchiectomy or GnRHa.
Any fractures, peripheral arterial disease, venous thromboembolism, cardiac-related complications, diabetes mellitus, and cognitive disorders. To minimize treatment group biases, the inverse probability of treatment was weighted using the propensity score. Multivariable competing risk regression models were performed with the adjustment of all-cause mortality. Secondary analyses examined the effect of increasing duration of GnRHa treatment. Multivariable logistic regression models examined expenditures.
Overall, 3295 men with a primary diagnosis of metastatic PCa treated with GnRHa or orchiectomy were identified between years 1995 and 2009, and in adjusted analyses, patients who received a bilateral orchiectomy had significantly lower risks of experiencing any fractures (hazard ratio [HR], 0.77; 95% CI, 0.62-0.94; P = .01), peripheral arterial disease (HR, 0.65; 95% CI, 0.49-0.87; P = .004), and cardiac-related complications (HR, 0.74; 0.58-0.94; P = .01) compared with those treated with GnRHa. No statistically significant difference was noted between orchiectomy and GnRHa for diabetes and cognitive disorders. In individuals treated with GnRHa for 35 months or more, the increased risk for GnRHa compared with orchiectomy was noted for fractures (HR, 1.80), peripheral arterial disease (HR, 2.25), venous thromboembolism (HR, 1.52), cardiac-related complications (HR, 1.69), and diabetes mellitus (HR, 1.88) (P ≤ .01 for all). At 12 months after PCa diagnosis, the median total expenditures was not significantly different between GnRHa and orchiectomy.
Gonadotropin-releasing hormone agonist therapy is associated with higher risks of several clinically relevant adverse effects compared with orchiectomy.
通过手术去势的雄激素剥夺疗法（ADT）在控制前列腺癌（PCa）方面与医学去势同样有效。然而，这两种 ADT 组的不良反应谱从未被比较过。
在同质人群中提供促性腺激素释放激素激动剂（GnRHa）与双侧睾丸切除术不良影响的比较效果分析。
设计、设置和参与者：从监测、流行病学和最终结果（SEER）-医疗保险相关数据库中选择了 1995 年 1 月至 2009 年 12 月间年龄在 66 岁或以上的 3295 名转移性 PCa 男性的基于人群的队列。
睾丸切除术或 GnRHa。
任何骨折、外周动脉疾病、静脉血栓栓塞、心脏相关并发症、糖尿病和认知障碍。为了最小化治疗组偏差，使用倾向评分对治疗的逆概率进行加权。使用全因死亡率进行了多变量竞争风险回归模型分析。次要分析检查了 GnRHa 治疗时间延长的效果。多变量逻辑回归模型检查了支出。
总体而言，在 1995 年至 2009 年间，对接受 GnRHa 或睾丸切除术治疗的 3295 名转移性 PCa 患者进行了原发性诊断，在调整后的分析中，接受双侧睾丸切除术的患者发生任何骨折的风险显著降低（风险比 [HR]，0.77；95% CI，0.62-0.94；P=0.01）、外周动脉疾病（HR，0.65；95% CI，0.49-0.87；P=0.004）和心脏相关并发症（HR，0.74；0.58-0.94；P=0.01）与接受 GnRHa 治疗的患者相比。睾丸切除术与 GnRHa 治疗在糖尿病和认知障碍方面无统计学差异。在接受 GnRHa 治疗 35 个月或更长时间的患者中，与睾丸切除术相比，GnRHa 治疗的骨折（HR，1.80）、外周动脉疾病（HR，2.25）、静脉血栓栓塞（HR，1.52）、心脏相关并发症（HR，1.69）和糖尿病（HR，1.88）的风险增加（所有 P 值均≤0.01）。在 PCa 诊断后 12 个月，GnRHa 和睾丸切除术之间的中位总支出无显著差异。
与睾丸切除术相比，促性腺激素释放激素激动剂治疗与更高的几种临床相关不良事件风险相关。
