TOPLINE:

A phase 3 study found that transdermal oestradiol (tE2) patches were non-inferior to luteinising hormone-releasing hormone (LHRH) agonists for 3‑year metastasis‑free survival in patients with locally advanced non-metastatic prostate cancer. They were also associated with reduced incidences of hot flashes but a higher incidence of gynaecomastia.

METHODOLOGY:

• Researchers conducted a phase 3, non-inferiority, randomised trial including 1360 men (median age, 72 years) with locally advanced (metastasis stage M0 and nodal stage N0 or N+) prostate cancer from PATCH and STAMPEDE-1 trial networks between 2007 and 2022.
• Patients were randomly assigned to receive either tE2 patches (100 μg of oestradiol every 24 hours; n = 721) or LHRH agonists (injected subcutaneously every 4 or 12 weeks; n = 639).
• Overall, 85% of patients had a tumour stage of T3, and 65% had a nodal stage of N0. The median prostate-specific antigen level during trial enrolment was 24.4 ng/mL.
• The primary outcome was 3-year metastasis-free survival. A prespecified non-inferiority margin of 4 percentage points corresponded to a target hazard ratio (HR) of 1.31, derived from the observed 3‑year metastasis‑free survival in the LHRH agonist cohort. Secondary outcomes included castrate levels of testosterone (< 1.7 nmol/L), overall survival, and safety.

TAKEAWAY:

• The observed 3-year metastasis-free survival was 87.1% with tE2 patches and 85.9% with LHRH agonists, with a HR for confirmed metastasis or death from any cause of 0.96 (upper limit of one-sided 95% CI, 1.11), meeting the criterion for non-inferiority.
• Among patients who continued the assigned treatment, castrate levels of testosterone were sustained during the first year after randomisation in 85% of those in each group, with similar proportions found at 3, 6, and 12 months.
• The observed 5-year overall survival was 81.1% with tE2 patches and 79.2% with LHRH agonists, with a HR for death of 0.90 (95% CI, 0.75-1.07), favouring tE2 patches.
• Hot flashes of grade 2 or higher occurred less frequently with tE2 patches than with LHRH agonists (8% vs 37%), whereas gynaecomastia of grade 2 or higher occurred more frequently with tE2 patches (37% vs 9%).

IN PRACTICE:

"Given these findings, tE2 patches can be considered an alternative choice for testosterone suppression in men with metastasis stage M0 and nodal stage N0 or N+ prostate cancer," the authors of the study wrote.

SOURCE:

This study was led by Ruth E. Langley, PhD, MRC Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology, London, England. It was published online on March 25, 2026, in The New England Journal of Medicine.

LIMITATIONS:

This trial was limited by the introduction of prostate radiotherapy as the standard of care and changes in the duration of androgen-deprivation therapy and systemic treatments. The median duration of treatment differed because patients switched from tE2 therapy to LHRH agonists for toxicity or progression, which may have influenced safety and long‑term outcome comparisons. Comparative data on the recovery of testosterone levels were not available, and data on quality-of-life measures were collected but have not yet been analysed.

DISCLOSURES:

This study received support through grants from Cancer Research UK and the UK Medical Research Council. Nine authors declared serving as consultants or receiving travel fees and having other ties with various sources. Full disclosures are available along with the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.