Effects of Relugolix vs Leuprolide on Cardiac Function in Patients With Prostate Cancer

PRIMARY OBJECTIVES: I. To quantify the physiologic alterations in cardiopulmonary function in men receiving 6-month relugolix verse (vs.) 6-month leuprolide with definitive radiation therapy (RT) for unfavorable intermediate risk (UIR) clinically localized prostate cancer (PCa). II. Cardiopulmonary and cardiac measures obtained from: 1) exercise stress cardiac magnetic resonance imaging (MRI) perfusion, and 2) maximal rate of oxygen consumption (VO2), include myocardial perfusion reserve index (MPRI), contractile reserve, myocardial longitudinal relaxation time (T1) signal, longitudinal strain, circumferential strain, VO2 maximum (max), and metabolic equivalents of exercise capacity (METs). SECONDARY OBJECTIVES: I. To quantify the impact of 6-month relugolix vs. leuprolide with definitive RT for UIR PCa on quality of life (QoL) using Expanded Cancer Index Composite (EPIC)-26, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), European (Euro) Qol-5-Dimension 5-level (EQ-5D-5L), and Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (Short Form 8a) patient-reported outcome surveys, or similar tests. II. To quantify the impact of 6-month relugolix vs. leuprolide on composite functional tests of strength and balance using three tests: 1) Timed Up-and-Go, 2) 10-meter walk time, and 3) grip strength. III. To analyze body composition changes in response to 6-month relugolix vs. leuprolide by using abdominal computed tomography (CT) or magnetic resonance imaging (MRI) to quantitate abdominal/visceral fat and lean muscle mass with utilization of SliceOmatic software. EXPLORATORY OBJECTIVES: I. To compare changes in serum steroid profiles (panel of 17 steroid hormone metabolites, Ohio State University Comprehensive Cancer Center \[OSUCCC Pharmacoanalytic Shared Resource \[PhASR\]) before, during and after 6-month relugolix vs. 6-month leuprolide with definitive RT for UIR PCa. II. To compare changes in cardiometabolic biomarkers in the following three categories: 1) glycemic control parameters (fasting glucose, fasting insulin, and connecting \[C\]-peptide), 2) lipid profiles (total cholesterol, triglyceride, low-density lipoprotein \[LDL\], high-density lipoprotein \[HDL\], and leptin/adiponectin ratio), 3) markers of the obesity-associated low-grade chronic inflammatory state (CRP, TGF-beta, and IL-6, and novel related immunoregulators), and targeted or non- targeted metabolomics or proteomics (by OSUCCC NPASR and PSR) depending on procurement of additional funds. III. To compare the time course of recovery for hormonal and cardiometabolic markers after completion of 6-month relugolix vs. 6-month leuprolide with definitive RT for UIR PCa. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive definitive therapy for prostate cancer with ADT (leuprolide via injection once every 3 months, for a total of 6 months) in the absence of disease progression or unacceptable toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing before starting ADT and at 6 months after starting ADT. Patients also undergo blood and urine sample collection throughout the study, as well as completion of quality-of-life questionnaires. ARM 2: Patients receive definitive therapy for prostate cancer with ADT (relugolix orally once daily for a total of 6 months) in the absence of disease progression or unacceptable toxicity and definitive radiotherapy within 90 days of starting ADT. Patients receive gadolinium-based contrast intravenously (IV) and undergo exercise-stress cardiac MRI perfusion and comprehensive exercise physiology testing before starting ADT and at 6 months after starting ADT. Patients also undergo blood and urine sample collection throughout the study, as well as completion of quality-of-life questionnaires. After completion of study treatment, patients are followed up at 1, 3, and 6 months.