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