Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer

Summary

Background: * There are several ways to treat prostate cancer. Researchers want to see how well a certain kind of imaging helps detect prostate cancer. They also want to see if a particular drug combination used before surgery will benefit people with prostate cancer that hasn't spread in the body (non-metastatic). The combination will be androgen deprivation therapy and enzalutamide. * The combination of androgen deprivation therapy and enzalutamide has been shown to make patients with advanced (metastatic disease) live longer. The investigators want to see if using it earlier can increase cure rate of surgery and identify genetic or molecular characteristics that are associated with better outcomes. Objectives: \- To develop better ways of detecting prostate cancer before and after pre-operative treatment. Eligibility: \- Men at least 18 years old with non-metastatic prostate cancer. They must be candidates for a radical prostatectomy. Design: * Participants will be screened with medical history, physical exam, and blood tests. They will have scans and X-rays. * Before starting the study drugs, participants will have: * Vital signs taken, medical history, and blood tests. * Electrocardiogram (ECG) heart test, with patches stuck on the skin. * Small piece of tumor removed (biopsy) using image guidance from magnetic resonance imaging (MRI) and ultrasound. * 3T multi-parametric magnetic resonance imaging (mpMRI). Participants will lie on a table that slides into a metal cylinder. A probe will be inserted in the rectum. They will be in the scanner for about 60 minutes, lying still. The scanner makes loud knocking sounds. Participants will get earplugs. * Participants will take the 2 study drugs for 6 months. * Enzalutamide is taken as 4 pills once a day. * Androgen deprivation therapy is given by injection 2 times over 6 months. * During these 6 months, participants will visit the clinic monthly. They will have physical exam, vital signs, and blood drawn. * After finishing the study drugs, participants will have another 3T mpMRI. Then they will have prostate removal surgery.

Timeline

Start

2015-06-03

Primary completion

2019-12-01

Completion

2024-06-11

Publications

• Wilkinson S, Ku AT, Lis RT, King IM, Low D, Trostel SY, Bright JR, Terrigino NT, Baj A, Summerbell ER, Heyward KE, Kartal S, Fenimore JM, Li C, Singler C, Vo B, Jansen CS, Ye H, Whitlock NC, Harmon SA, Carrabba NV, Atway R, Lake R, Takeda DY, Kissick HT, Pinto PA, Choyke PL, Turkbey B, Dahut WL, Karzai F, Sowalsky AG. Localized high-risk prostate cancer harbors an androgen receptor activity-low subpopulation susceptible to HER2 inhibition. J Clin Invest. 2025 Sep 4;135(22):e189900. doi: 10.1172/JCI189900. eCollection 2025 Nov 17.
• Rathi N, Blake Z, Hyman J, Nemirovsky DR, Gelikman DG, Hesswani C, Koller C, Nethala D, Mendhiratta N, Kenigsberg AP, Noun J, Dahut W, Karzai FY, Linehan WM, Pinto PA, Turkbey B, Gurram S. Castration Levels of Testosterone Results in Atrophy of Androgen-sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism. Urology. 2025 Feb;196:313-320. doi: 10.1016/j.urology.2024.10.006. Epub 2024 Oct 18.
• Karzai F, Walker SM, Wilkinson S, Madan RA, Shih JH, Merino MJ, Harmon SA, VanderWeele DJ, Cordes LM, Carrabba NV, Bright JR, Terrigino NT, Chun G, Bilusic M, Couvillon A, Hankin A, Williams MN, Lis RT, Ye H, Choyke PL, Gulley JL, Sowalsky AG, Turkbey B, Pinto PA, Dahut WL. Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response. Clin Cancer Res. 2021 Jan 15;27(2):429-437. doi: 10.1158/1078-0432.CCR-20-2344. Epub 2020 Oct 6.
• Gold SA, VanderWeele DJ, Harmon S, Bloom JB, Karzai F, Hale GR, Marhamati S, Rayn KN, Mehralivand S, Merino MJ, Gulley JL, Bilusic M, Madan RA, Choyke PL, Turkbey B, Dahut W, Pinto PA. mpMRI preoperative staging in men treated with antiandrogen and androgen deprivation therapy before robotic prostatectomy. Urol Oncol. 2019 Jun;37(6):352.e25-352.e30. doi: 10.1016/j.urolonc.2019.01.012. Epub 2019 Apr 15.

Drugs

Indications