Transdermal oestradiol and exercise in androgen deprivation therapy (ESTRACISE): protocol.

OBJECTIVE: To report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise. STUDY DESIGN AND METHODS: The primary endpoint of this open-label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT-induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high-risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT-only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme. RESULTS: The primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT-induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life. CONCLUSION: The ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown. TRIAL REGISTRATION: The protocol has been registered in euclinicaltrials.eu (2023-504704-28-00) and in clinicaltrials.gov (NCT06271551).

Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy-A Randomized, Double-blind, Placebo-controlled Clinical Trial.

We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve prostate cancer patients scheduled for radical prostatectomy were randomized to use 80mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Blinding was maintained throughout the trial. In total, 158 men completed the follow-up, with 96% compliance. Overall, atorvastatin did not significantly lower tumor proliferation index Ki-67 or serum prostate-specific antigen (PSA) compared with placebo. In subgroup analyses, after a minimum of 28 d of atorvastatin use, Ki-67 was 14.1% lower compared with placebo (p = 0.056). Among high-grade cases (International Society of Urological Pathology Gleason grade 3 or higher), atorvastatin lowered PSA compared with placebo: median change -0.6 ng/ml; p = 0.024. Intraprostatic inflammation did not differ between the study arms (p = 0.8). Despite a negative overall result showing no effect of statins on Ki67 or PSA overall, in post hoc exploratory analyses, there appeared to be benefit after a minimum duration of 28 d. Further studies are needed to verify this. PATIENT SUMMARY: Cholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure.