Transdermal Estradiol Patches in Locally Advanced Prostate Cancer.

With tE2, testosterone is suppressed, and the side effects of estrogen depletion due to LHRH agonists and the thromboembolic side effects of oral estrogen are mitigated.

使用tE2可以抑制睾酮，并减轻LHRH激动剂引起的雌激素缺乏副作用以及口服雌激素的血栓栓塞副作用。

Methods

In this phase 3, noninferiority, randomized trial, we assigned men with locally advanced (M0 and N0 or N+) prostate cancer to receive tE2 patches (100 μg of estradiol every 24 hours) or LHRH agonists.

在这项 III 期、非劣效性、随机试验中，我们将局部晚期（M0 和 N0 或 N+）前列腺癌的男性患者分配接受 tE2 贴片（每24小时100微克雌二醇）或 LHRH 激动剂治疗。

The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratioof 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group.

主要结果是3年无转移生存率。非劣效性边界为4个百分点；这对应于从LHRH激动剂组观察到的3年无转移生存率推导出的目标风险比为1.31。

Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety.

次要结果包括去势水平的睾酮（<1.7纳摩尔/升），总生存和安全性。

Results

Between 2007 and 2022, we recruited 1360 patients at 75 U.K. centers.

在2007年至2022年间，我们在英国的75个中心招募了1360名患者。

The median age of the patients was 72 years (interquartile range, 68 to 77); 85% had a T3 tumor stage and 65% an N0 nodal stage.

患者的中位年龄为72岁（四分位数范围，68至77岁）；85%的患者肿瘤分期为T3期，65%的患者淋巴结分期为N0期。

Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratiofor confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval[CI], 1.11, which met the criterion for noninferiority).

观察到的3年无转移生存率为87.1%使用tE2和85.9%使用LHRH激动剂（确认转移或死亡的风险比为0.96；单侧95%置信区间[CI]的上限为1.11，满足非劣效性标准）。

Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group.

在继续接受指定治疗的患者中，随机化后第一年期间，每组均有85%的患者维持了去势水平的睾酮。

Observed 5-year overall survivalwas 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratiofor death, 0.90; 95% CI, 0.75 to 1.07).

观察到的5年总生存率为使用tE2的患者为81.1%，使用LHRH激动剂的患者为79.2%（死亡风险比为0.90；95%置信区间，0.75至1.07）。

During treatment, hot flashes occurred in 44% of the patients who received tE2 and 89% of those who received LHRH agonists (grade ≥2 events, 8% and 37%, respectively) and gynecomastia in 85% and 42% (grade ≥2 events, 37% and 9%).

治疗期间，44%接受tE2治疗的患者和89%接受LHRH激动剂治疗的患者出现了热潮红（≥2级事件分别为8%和37%），以及85%和42%的患者出现了男性乳房发育（≥2级事件分别为37%和9%）。

Conclusions

In patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidenceof hot flashes but a higher incidenceof gynecomastia.

在局部晚期前列腺癌患者中，tE2在3年无转移生存方面不劣于LHRH激动剂，热潮红的发生率较低，但男性乳房发育的发生率较高。

(Funded by Cancer Research U.K. and the U.K.

(由英国癌症研究慈善机构和英国

Research Institute Medical Research Council; PATCH ClinicalTrials.gov number, NCT00303784; STAMPEDE-1 ClinicalTrials.gov number, NCT00268476.).

医学研究委员会资助; PATCH临床试验注册号, NCT00303784; STAMPEDE-1临床试验注册号, NCT00268476.)