Transdermal Estradiol Patches in Locally Advanced Prostate Cancer

[madman]

* 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.

https://www.nejm.org/doi/full/10.1056/NEJMoa2511781?query=featured_home

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.

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METHOD

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%).

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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.)

 

[madman]

https://www.urologytimes.com/view/estradiol-and-adt-lessons-from-lived-experience

Estradiol and ADT: Lessons from Lived Experience​

In this opening segment, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss the origins, goals, and challenges of the Estradiol Initiative.


In this Rx Review video series from Urology Times, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss the Estradiol Initiative, a movement advocating for transdermal estradiol as a standard-of-care option for androgen deprivation therapy (ADT) in men with advanced prostate cancer. Drawing on extensive research, clinical experience, and their own long-term personal use, they argue that transdermal estradiol provides testosterone suppression and disease control equivalent to conventional LHRH-based ADT while offering markedly better quality of life, including fewer hot flashes, less fatigue, improved mood and sleep, and preservation of bone health. They emphasize that historical concerns about estrogen-related cardiovascular risk stem from oral delivery methods and are not seen with transdermal administration, a distinction supported by data from the PATCH trials. The speakers also highlight the therapy’s low cost, compatibility with modern combination regimens, and potential to reduce financial and skeletal complications associated with standard ADT. Despite barriers such as off-label status, lack of industry sponsorship, and lingering clinician skepticism, they contend that education and guideline inclusion are essential to ensure patients have informed access to this effective and patient-centered therapy option.

 

[madman]

https://www.urologytimes.com/view/economic-and-educational-barriers-to-estradiol-therapy-in-prostate-cancer

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Economic and Educational Barriers to Estradiol Therapy in Prostate Cancer​

In part 2 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, explore the historical, clinical, and systemic barriers to using transdermal estradiol as a treatment for prostate cancer, while highlighting its potential benefits.

Transdermal estradiol is emerging as a promising, patient-centered therapy for prostate cancer, yet its adoption is hindered by historical perceptions, clinical workflow norms, and systemic barriers. In part 2 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, explore the historical, clinical, and systemic barriers to using transdermal estradiol as a treatment for prostate cancer, while highlighting its potential benefits. Schellhammer begins by outlining the historical context: VA studies from the 1950s and 1960s demonstrated that oral estrogen could effectively control prostate cancer but carried significant cardiovascular and thromboembolic risks. These findings largely discredited estrogen therapy, a perception that persists today, in part because the biology of enterohepatic circulation and differences between oral and transdermal estrogen are not well appreciated.

 

[madman]

https://www.urologytimes.com/view/estradiol-patches-in-prostate-cancer-evidence-and-impact

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Estradiol Patches in Prostate Cancer: Evidence and Impact​

In part 3 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss emerging evidence supporting transdermal estradiol as an effective and potentially superior alternative to traditional LHRH analogue ADT for advanced prostate cancer.

Work from the Estradiol Initiative highlight transdermal estradiol as a promising alternative to traditional androgen deprivation therapy (ADT) for advanced prostate cancer. In part 3 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss emerging evidence supporting transdermal estradiol as an effective and potentially superior alternative to traditional LHRH analogue ADT for advanced prostate cancer. A key barrier to adoption has been concern about survival benefit, which they address by referencing long-term data from the PATCH trial. This large study, involving more than 1600 patients since 2007, demonstrates that transdermal estradiol provides equivalent time to metastasis and overall therapeutic efficacy compared with standard LHRH-based ADT.

 

[madman]

https://www.urologytimes.com/view/managing-gynecomastia-in-men-using-transdermal-estradiol

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Managing Gynecomastia in Men Using Transdermal Estradiol​

In part 4 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, focus on concerns about the adverse events of transdermal estradiol, particularly gynecomastia.

Transdermal estradiol is emerging as an alternative therapy for men experiencing adverse events from standard androgen deprivation treatments. In part 4 of a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, focus on concerns about the adverse events of transdermal estradiol, particularly gynecomastia, and how these concerns should be communicated to clinicians and patients. Schellhammer notes that gynecomastia and nipple or breast tenderness are often raised as immediate objections by physicians. When framed negatively—such as telling men they will “grow breasts”—this adverse event can prematurely end shared decision-making, despite potential benefits like relief from hot flashes.

Thread 'Gynecomastia: Approach to Evaluation and Management of a Common Disorder'

Dec 14, 2023

Dr. Sathya Krishnasamy gave a comprehensive overview of gynecomastia, covering its definition, prevalence, hormonal regulation, pathogenesis, differentials, and management options. He discussed the role of androgen receptor and aromatase in breast development, as well as the impact of various drugs, tumors, and environmental factors on gynecomastia. The session also included a case study and highlighted the importance of a thorough evaluation to determine the underlying cause, along with potential treatment options.


Highlights:

• ...

• madman
• gynecomastia evaluation and management
• Replies: 33
• Forum: Testosterone Side Effect Management

 

[madman]

https://www.urologytimes.com/view/why-guideline-support-is-key-to-estradiol-adoption-in-prostate-cancer

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Why Guideline Support Is Key to Estradiol Adoption in Prostate Cancer​

In the final installment in a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss strategies for establishing transdermal estradiol as a recognized therapy for men undergoing androgen deprivation therapy for prostate cancer.

For men on long-term prostate cancer therapy, quality of life matters. In the final installment in a 5-part series, Richard Wassersug, PhD, and Paul F. Schellhammer, MD, FACS, discuss strategies for establishing transdermal estradiol as a recognized therapy for men undergoing androgen deprivation therapy (ADT) for prostate cancer. They emphasize the need to present compelling evidence to patients, physicians, payers, and licensing authorities, highlighting that no pharmaceutical companies currently produce estradiol products specifically licensed for men. Schellhammer shares his personal experience with intermittent estradiol therapy during clinical trials, noting its positive impact on quality of life compared with traditional LHRH analogues.

 

[madman]

Thread 'Transdermal estradiol for androgen suppression in locally advanced prostate cancer'

Nov 8, 2024

Transdermal estradiol for androgen suppression in locally advanced prostate cancer​

Duncan Gilbert, MA, MRCP, FRCR, PhD, University College London, London, UK, discusses the Phase III PATCH trial (ISRCTN70406718), which investigated transdermal estradiol as an alternative to traditional androgen suppression (LH-RH analogues) in men with locally advanced, treatment-naive prostate cancer. Patients from the STAMPEDE trial (ISRCTN78818544) were additionally recruited and results from the locally advanced cohort were presented. Patients were randomized...

• madman
• advanced pca; transdermal estradiol; lh-rh
• Replies: 5
• Forum: Prostate Related Issues