近日，英国伦敦大学学院Ruth E. Langley团队报道了经皮雌二醇贴剂治疗局部晚期前列腺癌的疗效与安全性。这一研究成果于2026年3月25日发表在《新英格兰医学杂志》上。

透皮雌二醇（tE2）可替代促黄体激素释放激素（LHRH）激动剂，作为前列腺癌患者的雄激素剥夺疗法。使用tE2可抑制睾酮水平，同时减轻LHRH激动剂所致的雌激素耗竭相关副作用以及口服雌激素的血栓栓塞副作用。

在这项3期、非劣效性、随机试验中，研究组将局部晚期（M0且N0或N+）前列腺癌男性患者分配至接受tE2贴剂（每24小时释放100μg雌二醇）或LHRH激动剂治疗。主要结局为3年无转移生存率。非劣效性界值为4个百分点；根据LHRH激动剂组观察到的3年无转移生存率推算，对应的目标风险比为1.31。次要结局包括睾酮达到去势水平（<1.7 nmol/L）、总生存期和安全性。

2007年至2022年间，研究组在英国75个中心招募了1360例患者。患者中位年龄为72岁（四分位距：68至77岁）；85%为T3期肿瘤，65%为N0期淋巴结状态。tE2组观察到的3年无转移生存率为87.1%，LHRH激动剂组为85.9%（确诊转移或死亡的风险比为0.96；单侧95%置信区间上限为1.11，符合非劣效性标准）。在继续接受指定治疗的患者中，两组在随机化后第一年内均有85%的患者维持了睾酮去势水平。tE2组观察到的5年总生存率为81.1%，LHRH激动剂组为79.2%（死亡风险比为0.90；95%置信区间：0.75至1.07）。治疗期间，潮热发生率在tE2组为44%，LHRH激动剂组为89%（≥2级事件分别为8%和37%）；男性乳房发育发生率分别为85%和42%（≥2级事件分别为37%和9%）。

研究结果表明，在局部晚期前列腺癌患者中，就3年无转移生存率而言，tE2不劣于LHRH激动剂，且tE2组潮热发生率较低，但男性乳房发育发生率较高。

附：英文原文

Title: Transdermal Estradiol Patches in Locally Advanced Prostate Cancer

Author: Ruth E. Langley, Duncan C. Gilbert, Stephen Mangar, Stuart Rosen, Ellie Bourmaki, Hannah L. Rush, Subramaniam Kananga Sundaram, Abdulla Alhasso, Roger Kockelbergh, Hoda Abdel-Aty, Claire L. Amos, Louise Brown, Simon Brown, Charlene Carvalho, Kitty Chan, Gerald Collins, William Cross, John Deighan, Sanjay Dixit, Trinh Duong, James Dyer, Joanna Gale, Silke Gillessen, Anna Griffiths, Marc Laniado, Anna Lydon, Neil McPhail, Archie MacNair, Sanjeev Madaan, John Marshall, David Matheson, Robin Millman, Wael Mohamed, Laura Murphy, Krishna Narahari, Christopher Parker, Miguel Panades, Alvan Pope, Arpita Raval, Angus Robinson, Martin Russell, Christopher Scrase, Matthew Sydes, Rafal Turo, Ram Venkitaraman, Simona Wade, Howard Kynaston, Gerhardt Attard, Nicholas D. James, Noel Clarke, Mahesh K. Parmar, Matthew Nankivell

Issue&Volume: 2026-03-25

Abstract:

Background

Transdermal estradiol (tE2) is an alternative to luteinizing hormone–releasing hormone (LHRH) agonists as androgen-deprivation therapy in patients with 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.

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. The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratio of 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group. Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety.

Results

Between 2007 and 2022, we recruited 1360 patients at 75 U.K. centers. 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. Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratio for confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval [CI], 1.11, which met the criterion for noninferiority). Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group. Observed 5-year overall survival was 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratio for death, 0.90; 95% CI, 0.75 to 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%).

Conclusions

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

DOI: NJ202603250000003

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2511781