Department of Urology, Brigham and Women's Hospital, Boston, MA.
Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA.
Urol Oncol. 2024 Dec;42(12):447.e1-447.e9. doi: 10.1016/j.urolonc.2024.05.026. Epub 2024 Jul 12.
Intermittent androgen deprivation therapy (iADT) alleviates some side effects of continuous (c) ADT in patients with prostate cancer (PC), but its relative impact on ADT-associated comorbidities is uncertain. We assessed real-world use of iADT and cADT and associated risk of cardiovascular and endocrine/metabolic events in patients with nonmetastatic (nm) PC.
This retrospective longitudinal cohort study included patients with nmPC initiating systemic ADT with gonadotropin-releasing hormone agonists (goserelin, histrelin, leuprolide, and triptorelin) or antagonists (degarelix) in the US Surveillance, Epidemiology and End Results-Medicare database (2010-2017), who had ≥ 36 months of continuous insurance coverage, unless death occurred, and did not receive chemotherapy or next-generation hormonal therapies during follow-up (through 2019). Risk of major adverse cardiovascular events (MACE [myocardial infarction, stroke, cardiomyopathy/heart failure, pulmonary embolism, ischemic heart disease, all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, and osteoporosis) were examined between cohorts. Inverse probability of treatment-weighted Cox regression models estimated adjusted hazard ratios (HRs) of the outcomes.
Of 10,655 eligible patients, 2,095 (19.7%) received iADT and 8,560 (80.3%) cADT. Median follow-up was 43.9 and 48.4 months and median ADT duration (excluding iADT gaps) was 22.0 and 13.5 months for the iADT and cADT cohorts, respectively. Patients receiving cADT had a lower risk of MACE vs. iADT (HR 0.90; 95% confidence interval [CI] 0.83-0.96). No difference in risk of endocrine/metabolic events was observed (HR 0.97; 95% CI 0.92-1.03). Subgroup analysis found that the difference in MACE was maintained in patients with a history of cardiovascular disease (HR 0.90; 95% CI 0.83-0.98) and eliminated in patients without (HR 0.94; 95% CI 0.82-1.08).
Patients with nmPC who received cADT had a lower risk of MACE and similar risk of endocrine/metabolic events vs. those who received iADT. Further research assessing both regimens is needed to inform treatment decisions.
间歇性雄激素剥夺疗法（iADT）可缓解前列腺癌（PC）患者连续（c）ADT 的一些副作用，但它对 ADT 相关合并症的相对影响尚不确定。我们评估了非转移性（nm）PC 患者中 iADT 和 cADT 的实际应用情况，以及与心血管和内分泌/代谢事件相关的风险。
这项回顾性纵向队列研究纳入了美国监测、流行病学和最终结果-医疗保险数据库（2010-2017 年）中接受促性腺激素释放激素激动剂（戈舍瑞林、亮丙瑞林、曲普瑞林）或拮抗剂（地加瑞克）开始全身 ADT 的 nmPC 患者，这些患者至少有 36 个月的连续保险覆盖期，除非死亡，且在随访期间（截至 2019 年）未接受化疗或下一代激素治疗。检查了主要不良心血管事件（MACE[心肌梗死、中风、心肌病/心力衰竭、肺栓塞、缺血性心脏病、全因死亡率]）和内分泌/代谢事件（糖尿病、高胆固醇血症、骨折和骨质疏松症）在队列之间的发生风险。通过逆概率治疗加权 Cox 回归模型估计了结局的调整后的危险比（HR）。
在 10655 名合格患者中，2095 名（19.7%）接受了 iADT，8560 名（80.3%）接受了 cADT。中位随访时间分别为 43.9 和 48.4 个月，iADT 和 cADT 队列的中位 ADT 持续时间（不包括 iADT 间隙）分别为 22.0 和 13.5 个月。与 iADT 相比，接受 cADT 的患者发生 MACE 的风险较低（HR 0.90；95%置信区间[CI]0.83-0.96）。未观察到内分泌/代谢事件风险的差异（HR 0.97；95%CI0.92-1.03）。亚组分析发现，在有心血管疾病病史的患者中，MACE 的差异仍然存在（HR 0.90；95%CI0.83-0.98），而在无病史的患者中则消除（HR 0.94；95%CI0.82-1.08）。
与接受 iADT 的患者相比，接受 cADT 的 nmPC 患者发生 MACE 的风险较低，而发生内分泌/代谢事件的风险相似。需要进一步评估两种方案的研究，为治疗决策提供信息。
