Transdermal estradiol (tE2) delivered via patch demonstrates comparable efficacy to luteinizing hormone-releasing hormone (LHRH) agonists in managing high-risk, locally advanced non-metastatic prostate cancer. The findings, presented at the European Society for Medical Oncology (ESMO) 2024 Congress, suggest tE2 could be a valuable alternative for androgen suppression, offering a different side effect profile and potentially improving patient choice.
Efficacy and Safety Profile
The open-label phase 3 study included 1360 patients initiating androgen deprivation therapy. Ruth E. Langley, PhD, of University College London, the lead investigator, highlighted that tE2 effectively reduces testosterone levels without the estrogen-depletion effects commonly associated with LHRH agonists, such as osteoporosis, adverse metabolic profiles, and hot flushes. The transdermal delivery method also circumvents the thromboembolic risks linked to oral estrogen by avoiding first-pass hepatic metabolism.
The primary outcome, metastasis-free survival (MFS), was comparable between the two treatment arms. The 3-year MFS rate was 86% in the LHRH agonist group and 87% in the tE2 group. Overall survival also showed no significant difference between the groups. However, notable differences emerged in the incidence of specific side effects. Hot flushes were more prevalent in the LHRH agonist group (89%) compared to the tE2 group (44%), while gynecomastia was more common with tE2 (85% vs 42%). Both groups achieved similar sustained castration rates of testosterone (≤1.7 nmol/L over 1 year).
Study Design and Patient Population
The study population comprised 1082 participants from the PATCH trial (NCT00303784) and 278 from the STAMPEDE trial (NCT00268476). Eligible patients had histologically confirmed newly diagnosed high-risk non-metastatic prostate cancer (locally advanced or node-positive) or relapsing prostate cancer with specific PSA criteria (PSA ≥4 ng/mL and doubling time <6 months; PSA ≥20 ng/mL; or node-positive disease).
Patients were randomized to receive either an LHRH agonist (n=639) or tE2 patches (n=721) delivering 100 mcg of estradiol every 24 hours, changed twice weekly for at least two years.
Clinical Implications and Future Directions
Dr. Langley emphasized the importance of offering patients choices in their treatment plans, stating, "There is no detriment in terms of prostate cancer outcomes or overall survival in starting androgen suppression with tE2. Importantly, tE2 provides choice for patients in terms of expected side effects and routes of administration, allowing for personalized treatment plans." She further suggested that tE2 should be considered a standard of care ADT option in patients with non-metastatic disease.
These findings provide clinicians with an additional tool for managing high-risk prostate cancer, potentially improving patient satisfaction and adherence through personalized treatment strategies.
