Transdermal Estradiol Patches Show Promise as Effective Alternative to LHRHa in Metastatic Prostate Cancer Treatment

Transdermal estradiol (tE2) patches combined with androgen receptor pathway inhibitors (ARPIs) demonstrated similar PSA responses to LHRHa plus ARPIs in metastatic prostate cancer. The STAMPEDE trial supports tE2 patches as a viable, cost-effective alternative for androgen deprivation therapy (ADT) with a distinct safety profile. This approach offers patients more treatment options with fewer cardiovascular risks compared to oral estrogen therapies.

Transdermal Estradiol Patches Show Promise as Effective Alternative to LHRHa in Metastatic Prostate Cancer Treatment

A recent study presented at the 2025 Genitourinary Cancers Symposium (ASCO GU) examined the use of transdermal estradiol (tE2) patches in combination with androgen receptor pathway inhibitors (ARPIs) for the treatment of metastatic prostate cancer. This research, based on findings from the phase 2 STAMPEDE trial (NCT00268476), found that the combination of tE2 patches and ARPIs resulted in prostate-specific antigen (PSA) responses that were comparable to those seen with luteinizing hormone-releasing hormone analogues (LHRHa) plus ARPIs. These results suggest that tE2 patches could serve as a viable alternative to traditional androgen deprivation therapy (ADT) in the management of prostate cancer, offering distinct benefits in terms of toxicity profiles and administration methods.

The STAMPEDE trial, which ran from October 2020 to March 2023, enrolled 79 patients with histologically confirmed M1 prostate cancer. These patients were randomly assigned to receive either LHRHa plus ARPIs (41 patients) or tE2 patches plus ARPIs (38 patients). The study aimed to compare the efficacy and safety of these two treatment combinations. At baseline, both groups were similar in terms of median age (69 years) and PSA levels (47 ng/ml for the LHRHa+ARPI group and 39 ng/ml for the tE2+ARPI group).

The primary outcome of the study was the proportion of patients who achieved a PSA nadir (the lowest level of PSA) of 0.2 ng/ml or less within the first six months of treatment. Results showed that 61% of patients in the LHRHa+ARPI arm and 61% of patients in the (Transdermal Estradiol) tE2+ARPI arm achieved this PSA target. Additionally, PSA90 rates (the percentage of patients who had a 90% reduction in PSA) were similar between the two groups, with 93% of LHRHa+ARPI patients and 95% of tE2+ARPI patients reaching this level. Both groups also had a 100% PSA50 rate, meaning all patients saw a 50% reduction in PSA.

In terms of testosterone suppression, which is a key aspect of ADT, 91% of patients in the (Transdermal Estradiol) tE2+ARPI group had testosterone levels of 1.7 ng/ml or less after 12 weeks of treatment. This indicates that tE2 patches were effective in reducing testosterone to castrate levels, a crucial part of prostate cancer treatment.

When it came to safety, the (Transdermal Estradiol) tE2+ARPI combination exhibited a different toxicity profile compared to LHRHa+ARPI. Among patients receiving LHRHa, 54% experienced hot flashes of any grade, while only 18% of patients in the tE2 group reported this side effect. Gynecomastia (breast tissue enlargement) was more common in the tE2 group, with 45% of patients experiencing it, compared to just 10% in the LHRHa group. Hypertension occurred in 20% of LHRHa-treated patients, but only 5% of those in the tE2 group. Pruritis (itchiness) was reported by 21% of tE2-treated patients and 5% of LHRHa-treated patients.

The tE2 patches used in the study delivered 100 mcg of estradiol per 24 hours, with patients changing the patches twice weekly. This transdermal method was chosen over oral estrogen therapies because it avoids the cardiovascular thromboembolic risks associated with oral administration while still effectively suppressing testosterone. As noted by presenting author Nicholas David James of The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, estrogen has long been recognized as a potent anti-cancer treatment, dating back to the 1940s. By using tE2 patches, the study aimed to harness estrogen’s therapeutic effects while minimizing its side effects.

The findings from this study suggest that (Transdermal Estradiol) tE2 patches, in combination with ARPIs, are not only effective at suppressing PSA levels and testosterone but also provide an option for patients who might prefer an alternative to LHRHa therapy, either for reasons of cost or side effect profile. The treatment is particularly appealing due to its affordability, making it an attractive choice for patients who may need to self-pay for their medications. No unexpected adverse events were observed in the study, and researchers concluded that tE2 patches are a safe and effective treatment option for men undergoing ADT for metastatic prostate cancer.

In conclusion, the combination of (Transdermal Estradiol)  tE2 patches and ARPIs offers a promising alternative to traditional LHRHa therapy for metastatic prostate cancer. With similar PSA responses, a different toxicity profile, and a more convenient method of administration, this treatment could provide patients with more choices and flexibility in their prostate cancer management.