Earlier this month, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology for Prostate Cancer to include transdermal estradiol as an androgen deprivation therapy (ADT) option for patients with localized and regional prostate cancer receiving radiation therapy. Transdermal estradiol is FDA-approved for estrogen-replacement indications, including the treatment of menopausal symptoms, but it is not FDA-approved for prostate cancer. Reboot Rx has been working with clinical experts to help translate the evidence on the repurposed use of transdermal estradiol into clinical practice.
“This NCCN update is an important development and addresses one of the major barriers to broader use of transdermal estradiol for patients with prostate cancer,” said Laura Kleiman, PhD, Founder and CEO of Reboot Rx, a nonprofit focused on drug repurposing in oncology. “It helps raise awareness of the evidence and gives clinicians greater confidence in considering transdermal estradiol for appropriate patients.”
The NCCN Guidelines update follows the Langley et al. 2026 publication in The New England Journal of Medicine (NEJM). This phase 3 randomized trial evaluated transdermal estradiol patches compared with luteinizing hormone-releasing hormone (LHRH) agonists, a standard of care ADT, in patients with locally advanced prostate cancer. Transdermal estradiol patches were noninferior to LHRH agonists for 3-year metastasis-free survival and offered a different side-effect profile.
LHRH agonists suppress testosterone and reduce estrogen. This estrogen depletion can lead to side effects such as hot flashes and loss of bone mineral density. On the other hand, transdermal estradiol patches suppress testosterone without reducing estrogen. In patients with prostate cancer, transdermal estradiol patches are associated with fewer hot flashes and less loss of bone mineral density than LHRH agonists, but a higher incidence of gynecomastia.
“The addition of transdermal estradiol to NCCN prostate cancer guidelines means there is another option to consider for ADT based on the individual preferences of patients,” said Ruth Langley, PhD, FRCP, Professor of Oncology & Clinical Trials at University College London and first author of the NEJM study. “Transdermal estradiol is a strong example of how repurposing an existing generic drug can expand treatment options for patients and provide lower-cost alternatives.”
While guideline inclusion is an important step toward clinical use, additional efforts are needed to support informed clinical decision-making, particularly because transdermal estradiol is not FDA-approved for prostate cancer. Reboot Rx is continuing to work with clinicians and other healthcare stakeholders to understand the remaining barriers to its use in clinical practice and support implementation.
Reboot Rx is a nonprofit dedicated to advancing affordable cancer treatments by repurposing generic drugs. The organization synthesizes and evaluates published clinical evidence on repurposed generic drugs for cancer in consultation with clinical experts, advances new clinical research through strategic partnerships, and develops and disseminates evidence-based information for clinicians, health systems, and other healthcare decision-makers.
Transdermal estradiol is one of several repurposed treatment opportunities Reboot Rx has identified and is working to advance. This year, the organization released two publicly available clinician resources: one on aspirin for patients with stage II–III PI3K-altered colorectal cancer and another on 5-alpha reductase inhibitors (5-ARIs) for patients with prostate cancer on active surveillance. Reboot Rx continues to pursue additional promising treatments. Learn more at rebootrx.org.
Transdermal estradiol is not FDA-approved for the treatment of prostate cancer. This press release is intended for informational purposes only and is not intended to provide medical advice. Clinicians should make individual prescribing decisions for their patients based on the patient’s clinical presentation and the clinician’s own medical decision-making.
