Hormone Therapy (Apalutamide) and Image-guided Stereotactic Body Radiation Therapy for the Treatment of Patients With Prostate Cancer, HEATWAVE Trial (HEATWAVE)

Inclusion Criteria: Confirmed diagnosis of prostate adenocarcinoma Age ≥ 18 Classified as having National Comprehensive Cancer Network unfavorable intermediate risk prostate cancer (i.e., [a] 2 of the following: PSA 10-20 ng/mL, clinical T category 2b-2c, or International Society of Urological Pathology [ISUP] grade group 2; [b] OR any 1 of [a] with ISUP grade group 3 disease; OR [c] any 1 of [a] with 50% or more cores on systematic biopsy showing prostate cancer) Have a Decipher genomic classifier score Have at least one dominant intraprostatic lesion visible on multiparametric MRI (Prostate Imaging-Reporting and Data System [PI-RADS] version 2.1 score 4 or 5) Have underwent a prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) Have total testosterone >= 150 ng/dL Adequate performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization (at screening) Platelet count ≥ 100,000 x 10^9/uL independent of transfusion and/or growth factors within 3 months prior to randomization (at screening) Serum albumin ≥ 3.0 g/dL (at screening) Glomerular filtration rate (GFR) ≥ 45 mL/min (at screening) Serum potassium ≥ 3.5 mmol/L (at screening) Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible) (at screening) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN (at screening) Medications known to lower the seizure threshold (see list under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study entry Exclusion Criteria: Any evidence of spinal cord compression (radiological or clinical) Prior pelvic malignancy Prior pelvic radiation Concurrent malignancy other than adequately treated basal cell or squamous cell skin cancer, non-muscle invasive bladder cancer (NMIBC), or any other cancer in situ currently without evidence of recurrence or progression Inability to undergo radiotherapy, or hormonal therapy Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed) Inflammatory bowel disease or active collagen vascular disease History of any of the following: Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy) Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization Current evidence of any of the following: Uncontrolled hypertension Gastrointestinal disorder affecting absorption Known active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis) Any condition that in the opinion of the investigator would preclude participation in this study Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate may be considered Baseline moderate and severe hepatic impairment (Child Pugh class B & C)