Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer

Inclusion Criteria:

* Confirmed diagnosis of prostate adenocarcinoma after radical prostatectomy (primary small cell carcinoma of the prostate is not allowed, however adenocarcinoma with neuroendocrine differentiation is allowed)
* Presence of 1-5 visible metastases (by PSMA PET-CT)

  * At least one metastasis must be M1a-b
  * Visceral metastases are not allowed
  * Patients may have any number of pelvic nodal metastases (but largest must be \< 2 cm)
  * Metastases must be amenable to treatment with SBRT
  * Biopsy of one metastasis must be attempted, unless unsafe to perform
* Patient must be fit to undergo SBRT to all visible sites of metastases, ADT
* Total testosterone \> 150 ng/dL prior to ADT (optimal time to measure total testosterone is between 8 and 9 am)
* 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
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors within 3 months prior to randomization
* Serum albumin \>= 3.0 g/dL
* Glomerular filtration rate (GFR) \>= 45 mL/min
* Serum potassium \>= 3.5 mmol/L
* Serum total bilirubin =\< 1.5 x upper limits 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
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5 x ULN
* Medications known to lower the seizure threshold 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 aside from salvage prostate radiation
* Concurrent malignancy aside from superficial skin cancers or superficial bladder tumors
* Inability to undergo radiotherapy, or ADT
* 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
  * Active infection (eg, human immunodeficiency virus \[HIV\] or viral hepatitis)
  * Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
  * Any condition that in the opinion of the investigator would preclude participation in this study
  * Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be co-administered, abiraterone acetate dose frequency will be adjusted). \[SAFETY: Warning against use with CYP2C8 inhibitors with narrow therapeutic index is also pertinent to be included as it is also part of United States Prescribing Information (USPI): In a CYP2C8 drug-drug interaction trial in healthy subjects, the area under curve (AUC) of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA\]
  * 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 (ChildPugh Class B \& C)
* Presence of visceral metastases (i.e., stage M1c)