TY - JOUR T1 - Transdermal Estradiol Patches in Locally Advanced Prostate Cancer. AU - Langley,Ruth E, AU - Gilbert,Duncan C, AU - Mangar,Stephen, AU - Rosen,Stuart, AU - Bourmaki,Ellie, AU - Rush,Hannah L, AU - Kananga Sundaram,Subramaniam, AU - Alhasso,Abdulla, AU - Kockelbergh,Roger, AU - Abdel-Aty,Hoda, AU - Amos,Claire L, AU - Brown,Louise, AU - Brown,Simon, AU - Carvalho,Charlene, AU - Chan,Kitty, AU - Collins,Gerald, AU - Cross,William, AU - Deighan,John, AU - Dixit,Sanjay, AU - Duong,Trinh, AU - Dyer,James, AU - Gale,Joanna, AU - Gillessen,Silke, AU - Griffiths,Anna, AU - Laniado,Marc, AU - Lydon,Anna, AU - McPhail,Neil, AU - MacNair,Archie, AU - Madaan,Sanjeev, AU - Marshall,John, AU - Matheson,David, AU - Millman,Robin, AU - Mohamed,Wael, AU - Murphy,Laura, AU - Narahari,Krishna, AU - Parker,Christopher, AU - Panades,Miguel, AU - Pope,Alvan, AU - Raval,Arpita, AU - Robinson,Angus, AU - Russell,Martin, AU - Scrase,Christopher, AU - Sydes,Matthew, AU - Turo,Rafal, AU - Venkitaraman,Ram, AU - Wade,Simona, AU - Kynaston,Howard, AU - Attard,Gerhardt, AU - James,Nicholas D, AU - Clarke,Noel, AU - Parmar,Mahesh K, AU - Nankivell,Matthew, AU - ,, Y1 - 2026/03/25/ PY - 2026/4/22/medline PY - 2026/3/25/pubmed PY - 2026/3/25/entrez SP - 1595 EP - 1607 JF - The New England journal of medicine JO - N Engl J Med VL - 394 IS - 16 N2 - 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. (Funded by Cancer Research U.K. and the U.K. Research Institute Medical Research Council; PATCH ClinicalTrials.gov number, NCT00303784; STAMPEDE-1 ClinicalTrials.gov number, NCT00268476.). SN - 1533-4406 UR - https://www.unboundmedicine.com/prime/citation/41880608/Transdermal_Estradiol_Patches_in_Locally_Advanced_Prostate_Cancer. DB - PRIME DP - Unbound Medicine ER -