Estradiol patches match standard hormone injections in prostate cancer

Suppressing testosterone with oestrogen skin patches worked as well as the standard hormone injections for men with locally advanced prostate cancer: in the phase 3 PATCH trial, three-year metastasis-free survival was 87.1% with transdermal estradiol and 85.9% with LHRH-agonist injections, meeting the trial's threshold for non-inferiority [s1]. The patches caused fewer hot flushes but more breast swelling, making the finding less about which treatment is better than about giving men a genuine choice between two side-effect profiles [s1].

Androgen-deprivation therapy — lowering testosterone to slow prostate cancer — is usually delivered with LHRH-agonist injections, which drive down the sex hormones and bring hot flushes, bone thinning and metabolic effects [s1]. Oestrogen can suppress testosterone too, and was largely abandoned decades ago because oral oestrogen caused dangerous blood clots. Delivering it through the skin was expected to keep the testosterone-lowering effect while avoiding that clot risk, and PATCH set out to test whether it also matched the cancer control of standard injections [s1]. Part of the appeal is that LHRH agonists produce the effects of oestrogen depletion — hot flushes and bone thinning among them — which keeping oestrogen in the body with a patch was expected to lessen [s1].

What they did

PATCH was a phase 3 randomised non-inferiority trial run within the STAMPEDE-1 platform, recruiting 1,360 men at 75 U.K. centres between 2007 and 2022 [s1]. Participants had locally advanced prostate cancer, defined as disease that had spread beyond the gland locally or to nearby lymph nodes but not to distant organs, and were assigned to either transdermal estradiol patches, delivering 100 micrograms of estradiol every 24 hours, or LHRH-agonist injections [s1][s2]. The median age was 72 years, 85% had a T3 tumour and 65% had no nodal spread [s1]. The primary outcome was three-year metastasis-free survival, with a pre-specified non-inferiority margin of 4 percentage points [s1]. In practice that meant the patches had to be shown to give up no more than 4 points of three-year metastasis-free survival to be judged an acceptable alternative — a threshold they cleared [s1].

A non-inferiority design does not try to show a new treatment is better; it asks whether it is not meaningfully worse than the standard, which is the right question when the appeal of the alternative is tolerability or cost rather than efficacy.

What it showed

Three-year metastasis-free survival was 87.1% with the patches and 85.9% with injections, a hazard ratio for metastasis or death of 0.96 with an upper limit of the one-sided 95% confidence interval of 1.11 — well inside the pre-specified margin, so the patches were declared non-inferior [s1]. Testosterone fell to castrate levels and stayed there through the first year in 85% of men in each group, confirming the patches suppress the hormone as reliably as injections [s1]. That biochemical result is the mechanistic check underneath the survival numbers: it shows the patches were not merely as safe but as effective at shutting down the testosterone that feeds the cancer [s1]. Five-year overall survival was likewise similar: 81.1% with estradiol and 79.2% with injections, a hazard ratio for death of 0.90 (95% confidence interval, 0.75 to 1.07) [s1]. On both the cancer-control and survival measures, then, the two approaches came out level, which is what turns the decision toward side effects and practicality rather than efficacy.

The side-effect trade

Where the two treatments diverged was tolerability, and not in one direction. Hot flushes occurred in 44% of men on the patches and 89% of those on injections, with moderate-or-worse flushes in 8% versus 37% [s1]. But breast swelling, or gynaecomastia, went the other way: it affected 85% of the estradiol group and 42% of the injection group, with moderate-or-worse swelling in 37% versus 9% [s1]. So the patches trade the flushes and, in principle, some of the bone and metabolic harms of oestrogen deprivation for a much higher rate of breast tenderness and enlargement. Neither profile is obviously preferable; which matters more is a question for the individual man, a theme that runs through the side effects of prostate-cancer treatment more broadly.

What to watch

PATCH is a notably independent trial — funded by Cancer Research UK and the Medical Research Council rather than a drug manufacturer, and testing an old, off-patent hormone with no commercial champion [s1]. That makes it exactly the kind of question industry rarely funds, and the answer is useful precisely because it widens choice rather than selling a product. The trial studied men with locally advanced disease, so it does not directly address hormone therapy in metastatic prostate cancer or in the many cases now managed by active surveillance without any hormone therapy at all. The longer-term cardiovascular and bone outcomes that motivated the switch to skin-delivered oestrogen will need continued follow-up to confirm, but on cancer control the case is now made.

Sources

• [s1] Langley RE, Gilbert DC, Mangar S, et al. Transdermal Estradiol Patches in Locally Advanced Prostate Cancer. New England Journal of Medicine. 25 March 2026.
• [s2] ClinicalTrials.gov. Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH, NCT00303784). U.S. National Library of Medicine.