Statin Induced Cholesterol Lowering Effect on Prolonged Castration Inhibition (Castration-Resistance Delay) May Navigate the Prostate Cancer Spread or Progress after Androgen Deprivation Therapy: Randomized double-blind phase 3 clinical study protoco

Introduction Cardioprotective statins keep cholesterol low in the blood. High blood cholesterol raises the risk of recurrent prostate cancer in patients with post-prostatectomy survivors with cardiac disease. The statins perform mainly two functions: 1. Statins prolong the time period to begin castration resistance during androgen deprivation therapy for prostate cancer; 2. Statins may biosense or navigate the prostate cancer spread as the predictor of the enhanced patient outcome. The present study protocol will test the statin action on delaying castration-resistance in a randomized placebo-controlled manner. Objectives and Aim: In present study, the protocol will have two objectives: 1. to test the castration-resistance delay efficacy of administered statins vs placebo before the development of castration resistance during androgen deprivation therapy in primary metastatic or recurrent prostate cancer; 2. to navigate the statin intervention effects such as low prostate cancer mortality and cholesterol-lowering to improve the patient outcomes better Materials and Methods: The protocol of random placebo-controlled double-blind trial on 500 males with metastatic or recurrent prostate cancer subjects will be included for androgen deprivation therapy (ADT). These males will receive daily dose of recommended low-doses or high doses of hydrophilic or hydrophobic statins vs placebo with no statins in randomized males in both statin or placebo-control groups. During whole study period until cancer persists or termination of trial. As lipid biomarkers, serum lipid profile (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides) will serve as cholesterol-lowering predictor of treatment response during ADT as primary outcome. The initial castration-resistance after ADT will be biosensing indicator of primary outcome. Simultaneous treatment response will be measured by AI-assisted digital MRI/PET images. Additional comparable benefit of statins may be on improved LONGLIVE lifestyle (less cardiovascular morbidity, normal blood sugar, circulating cell-free DNA, urine lipidome). Patient Ethics: The proposed protocol will be subject to approval of the study by local institution ethical committee set up at proposed institution such as Government Medical College, Saharanpur UP, India. All male participants will read the consent form and sign the informed consent form before their entry in the study as blinded participant beginning to end of study. The results will be published for the primary endpoints, anonymous summary metadata and statistical code. All these reports will be made available to all with no participant information. Clinical Study Registration Number: ICMR/IITR-GMC Academy 2024/PC-003