Dexamethasone Prior to Re-treatment With Enzalutamide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Enzalutamide and Docetaxel

Inclusion Criteria: * Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate * Patients must have metastatic disease radiographically documented by CT/magnetic resonance imaging (MRI) or bone scan; measurable disease is not necessary for inclusion * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Life expectancy of greater than 3 months in the opinion of the investigator * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Hemoglobin \>= 8; transfusion is allowed * Total bilirubin =\< 1.5 x institutional upper limit of normal * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal * Creatinine clearance \>= 30 by Cockcroft-Gault formula * Patients must have progression after prior treatment with Enza at any point in the disease course (pre- or post-chemotherapy) * Patients must have progressed after prior treatment with docetaxel; docetaxel must have specifically been given for castration-resistant metastatic disease * Prior treatment with other second line hormone therapy is allowed (e.g. flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, ARN-509); patients must be off these therapies for at least 4 weeks prior to starting treatment * Prior treatment with Xofigo (223Radium), Provenge, mitoxantrone and cabazitaxel is allowed * Patients must have rising PSA on two successive measurements, at least 2 weeks apart * Patient must be treated with continuous androgen ablative therapy (e.g. goserelin, leuprolide, triptorelin, or degarelix, if he has not had prior surgical castration) and have castrate levels of testosterone (\< 50 ng/dL or 1.7 nmol/L) * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (persistent toxicity \>= grade 1) * Patients who have received any other investigational agents within the last 4 weeks * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Dex or Enza * Any use of systemic corticosteroids in the prior 4 weeks * Uncontrolled diabetes mellitus * History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformations * Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) are ineligible (e.g. gemfibrozil, rifampin, trimethoprim, pioglitazone) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations or geographical condition that would limit compliance with study requirements