Apalutamide in Treating Patients With Prostate Cancer Who Are in Active Surveillance

Inclusion Criteria:

* Have signed an informed consent document
* Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
* Written authorization for use and release of health and research study information has been obtained
* Life expectancy \>= 10 years (as determined by the treating physician)
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
* Histologically confirmed adenocarcinoma of the prostate as documented by a minimum 12 core prostate biopsy completed within 1-year of enrollment (note: most recent prostate biopsy must have demonstrated prostatic adenocarcinoma)
* Favorable risk prostate cancer as defined by:

  * Very low-risk:

    * Clinical stage T1c disease
    * PSA density (PSAD) \< 0.15 ng/mL
    * Gleason score 6
    * =\< 2 core biopsies with =\< 50% involvement of any biopsy core with cancer, or unilateral disease =\< 2 core biopsies with any percentage involvement OR
  * Low risk:

    * Clinical stage =\< T2a
    * PSA \< 15 ng/mL
    * Gleason score 6 OR
  * Low-intermediate risk:

    * Clinical stage T1c
    * PSA \< 15 ng/ml
    * Gleason 3+4 present in =\< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy
    * Gleason 6 disease in all other cores / sites
* Willing and qualified for active surveillance at Johns Hopkins or the University of Washington
* Serum testosterone \>= 150 ng/dL
* Able to swallow the study drugs whole as a tablet
* Hemoglobin \>= 9.0 g/dL, (at screening), independent of transfusion and/or growth factors within 3 months prior to registration
* Platelet count \>= 100,000 x 10\^9/uL (at screening) independent of transfusion and/or growth factors within 3 months prior to registration
* 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) (at screening) (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 × ULN (at screening)
* Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
* Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:

* Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
* Prior use of ARN-509 (apalutamide)
* Have known allergies, hypersensitivity, or intolerance to ARN-509 (apalutamide) or its excipients
* Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

  * Hormonal therapy (e.g. leuprolide, goserelin, triptorelin)
  * Cytochrome P450 (CYP)-17 inhibitors (e.g. abiraterone, ketoconazole)
  * Antiandrogens (e.g. bicalutamide, nilutamide)
  * Second generation antiandrogens (e.g. enzalutamide)
  * Immunotherapy (e.g. sipuleucel-T, ipilimumab)
  * Chemotherapy (e.g. docetaxel, cabazitaxel)
* Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
* History of any of the following:

  * Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to registration, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  * Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration
  * Any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:

  * Uncontrolled hypertension
  * Gastrointestinal disorder affecting absorption
  * Active infection (e.g. human immunodeficiency virus \[HIV\] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
  * Any condition that in the opinion of the investigator, would preclude participation in this study
* The use of drugs known to lower the seizure threshold, including: atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone), bupropion, lithium, meperidine, pethidine, phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine), and tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
* The use of strong CYP3A4 inhibitors, including: itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice (or grapefruits)

  * Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide
* Strong CYP3A4 inducers, including: phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, efavirenz, tipranavir, St. John's wort

  \*\*Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide
* Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule