A new phase 2 study from the STAMPEDE trial suggests that transdermal estradiol (tE2) patches may be a safer and equally effective alternative to traditional luteinizing hormone-releasing hormone analogues (LHRHa) for patients with metastatic prostate cancer receiving androgen receptor pathway inhibitors (ARPIs). The trial compared the ability of these two hormone suppression strategies to reduce prostate-specific antigen (PSA) levels, a key marker of treatment response in prostate cancer.

The study found that PSA responses were similar between the two groups:

The PSA90 response rate (patients achieving a 90% reduction in PSA) was comparable between tE2 and LHRHa.
The PSA50 response rate (50% PSA reduction) was identical across both treatment groups.
This suggests that tE2 patches are just as effective as LHRHa in suppressing testosterone and controlling cancer growth when combined with ARPIs.

Beyond similar effectiveness, tE2 patches demonstrated a better safety profile in some areas:

Fewer hot flashes and lower rates of hypertension compared to patients receiving LHRHa, indicating better tolerance.

Better bone health: Previous research suggests that estradiol may help preserve bone density, a key concern for prostate cancer patients undergoing long-term androgen deprivation therapy (ADT).

Lower treatment costs: Transdermal estradiol may offer a cheaper and more accessible option compared to injectable or implanted LHRHa therapies.

However, breast tissue enlargement (gynecomastia) was more common in patients receiving tE2, a known side effect of estrogen-based therapies.

For decades, LHRHa has been the standard of care for hormone suppression in prostate cancer, despite its significant side effects, including increased cardiovascular risks, osteoporosis, and metabolic issues. The STAMPEDE trial’s findings suggest that transdermal estradiol patches may be a viable alternative—one that maintains efficacy while potentially improving quality of life for patients.

Further studies are needed to confirm long-term safety and survival benefits, but these findings open the door for new treatment strategies that could redefine androgen suppression therapy in metastatic prostate cancer.

Source.