Embraced when discovered by Huggins in 1940, âhormone therapyâ (androgen deprivation therapy (ADT)) for advanced prostate cancer, using oral estradiol (E2) was abandoned following data revealing good cancer specific but poor overall survival. Replaced by Luteinizing Hormone Releasing Hormone analogues (LHRHa), testosterone (T), but also E2, were suppressed to castrate levels. Toxicities resulted, remaining clinically and financially burdensome. The Phase III PATCH (Prostate Adenocarcinoma Trans-Cutaneous Hormones) trial, re-explores benefits and toxicities of E2 (transdermally) vs LHRHa. Transdermal E2 offers single medication effective both as ADT yet simultaneously mitigating toxicity. PATCH has enabled new hypotheses concerning sex hormone deficiency to be addressed.
Summaries of sub-studies include: Cognitive: previously well men in the 3-12 months of LHRHa ADT achieving castrate T were divided into 2 groups, impaired/not, (they, family/friends were asked re changes consistent with cognitive impairment). They underwent complex neuro-psychometric testing, positron emission tomography scanning and structural/functional magnetic resonance imaging. Odour: 10 men starting LHRHa ADT provided axillary sweat on t-shirts worn over 2 successive nights pre and 3 months post-treatment. Non-cancer controls provided samples for comparison. Sweat samples were frozen at -80'C until rated simultaneously for masculinity, attractiveness and intensity by adult females. Bone: Dual Energy Xray Absorpiomery (DEXA), Computed Tomography (CT) scans performed at corresponding time points were identified (n = 20). Bone mineral density (BMD), bone volume fraction (BVF) metrics and finite-element analysis (FEA) for digital strength is underway.
Cognitive: Preliminary results suggest memory, executive function deficits plus diffuse cortical neuroinflamation.Odour: data are currently being analyzed.Bone: Comparisons made between BMD, BVF and FEA bone strength, potentially suggest superiority of CT to assess fracture risk.
Conclusion PATCH reflects potential for addressing hypotheses additional to main primary and secondary end-points of a large clinical trial through design and performance of novel sub-studies
Clinical trial identification
All authors have declared no conflicts of interest.