PROSTATE-IQ: Parallel RandOmized STudy of Personalized Apalutamide Treatment and Evaluation to Improve Quality of Life in Post-Operative Radiation With Androgen Axis Suppression. A Phase III Multi-center Study for Men With Detectable PSA After Prostatectomy for Prostate Cancer.

1. Personalize treatment for prostate cancer based on how aggressive the disease is and 2. Learn if apalutamide-based treatment can help to reduce fatigue and other side effects of treatment in participants who are being treated with radiation therapy for prostate cancer, as compared to standard therapy.

Primary Objective: ARTERA LOW COHORT (less aggressive disease) 1\) To compare fatigue at 9 months, as assessed by FACIT-F, between participants assigned to six months of apalutamide monotherapy versus six months of GnRH-based ADT. HIGHER RISK COHORT (more aggressive disease) 1\) To compare fatigue at 24 months, as assessed by FACIT-fatigue, between participants assigned to six months of GnRH-based ADT plus apalutamide monotherapy versus 24 months of GnRH-based ADT. Secondary Objectives for both Cohorts: 1. To compare patient-reported quality of life for the two treatment arms (Arm 1 vs. 2 for Artera-Low Cohort and Arm 3 vs. 4 for Artera-High Cohort) as measured by FACT-P and EPIC-26. 2. To compare physician-reported toxicity for the two treatment arms as measured by CTCAE v 5. 3. To compare patient-reported activity levels for the two treatment arms as measured by the leisure-time activity questionnaire. 4. To compare patient activity and sleep for the two treatment arms as measured by participant wearable health bands. 5. To compare cognitive function for the two treatment arms as measured by PROMIS-CF and the Symbol Digit Modality test. 6. To compare mental health for the two treatment arms as measured by the Health Anxiety and Depression Scale. 7. To compare changes in HgA1c and Lipid profiles over time between the two treatment arms. 8. To compare time to testosterone recovery between treatment arms. 9. To compare time to next therapy between treatment arms. 10. To compare progression-free survival, metastasis-free survival, cancer specific mortality and overall survival between treatment arms. 11. To compare risk of major acute coronary event between treatment arms. 12. In the subset of patients who agree to optional body composition measurements, to compare change in body composition including visceral fat and skeletal muscle mass between treatment arms. Exploratory Objectives for both Cohorts: 1. In the subset of participants who agree to correlative studies, to evaluate the association between fatigue and circulating inflammatory cytokines. 2. In the subset of participants who agree to germline testing, to determine if inherited variants in steroidogenic genes influence individual body composition toxicity with androgen signaling inhibition. 3. To evaluate how germline variants interact with tumor intrinsic properties (via Artera) to determine the overall benefit patients derive from finite, intense androgen signaling inhibition in the post-operative setting. 4. To investigate the relationship between plasma exosomes, Artera tissue pattern, and the germline to somatic interaction. 5. To study the overlap between body composition toxicity and risk for coronary artery disease as measured by radiographic coronary calcifications and lab markers of coronary artery disease. 6. To evaluate the association between radiation plan metrics and patient-reported urinary and bowel functional changes.