Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer

Inclusion Criteria: 1. Biopsy confirmed diagnosis of prostate adenocarcinoma (primary small cell carcinoma of the prostate is not allowed, however adenocarcinoma with neuroendocrine differentiation is allowed) 2. Age 18 3. Presence of 1-5 visible metastases (by NaF PET-CT or PSMA PET-CT including diagnostic CT of the chest, abdomen, and pelvis) 1. At least one metastasis must be M1a-b 2. Visceral metastases are not allowed 3. Patients may have any number of pelvic nodal metastases (but largest must be \<2 cm) 4. Metastases must be amenable to treatment with SBRT 5. Biopsy of one metastasis must be attempted, unless unsafe to perform. If biopsy is not diagnostic, or unsafe to perform, then a secondary imaging modality (for example, MRI) must also be consistent with metastatic disease (unless PSMA PET-CT was used as initial staging). 4. Patient must be fit to undergo radical prostatectomy, SBRT to all visible sites of metastases, ADT, 5. Total testosterone \>200 ng/dL prior to ADT (optimal time to measure total testosterone is between 8 and 9 am) 6. Adequate performance status (ECOG 0-1) 7. Clinical laboratory values at screening: 1. Hemoglobin 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization 2. Platelet count 100,000 x 109/ L independent of transfusion and/or growth factors within 3 months prior to randomization 3. Serum albumin 3.0 g/dL 4. GFR 45 mL/min 5. Serum potassium 3.5 mmol/L 6. Serum total bilirubin 1.5 ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 ULN, measure direct and indirect bilirubin and if direct bilirubin is 1.5 ULN, subject may be eligible) 7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<2.5 ULN 8. 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: 1. Any evidence of spinal cord compression (radiological or clinical) 2. Prior pelvic malignancy 3. Prior pelvic radiation 4. Concurrent malignancy aside from superficial skin cancers or superficial bladder tumors 5. Inability to undergo prostatectomy, radiotherapy, or ADT 6. Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed) 7. Inflammatory bowel disease or active collagen vascular disease 8. History of any of the following: 1. Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy) 2. 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 9. Current evidence of any of the following: 1. Uncontrolled hypertension 2. Gastrointestinal disorder affecting absorption 3. Active infection (eg, human immunodeficiency virus \[HIV\] or viral hepatitis) 4. Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily 5. Any condition that in the opinion of the investigator would preclude participation in this study 6. Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be co-administered, abiraterone acetate dose frequency will be adjusted). 7. 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. 8. Baseline severe hepatic impairment (ChildPugh Class B \& C) 10. Presence of visceral metastases (i.e., stage M1c)