Conventional Androgen Deprivation Therapy (ADT) With or Without Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and ADT

Inclusion Criteria:

* In order to ensure a homogenous population at study entry, a bone scan and not a PET will be used to ensure M0 high risk prostate cancer. A bone scan is to be done up to 6 months prior to the start of initial ADT therapy or up to one month after initiation of ADT to rule out bony metastatic disease.
* Histologically confirmed prostate cancer
* PSA\> undetectable (any value at or above the lower limit of detection for the assay used) after radiation and at least 6, but not more than 12 months of conventional ADT (LHRH agonist or antagonist with or without oral anti androgens, excluding abiraterone acetate and apalutamide) in patients with non-metastatic high risk or N1 prostate cancer

  * High risk is defined per the NCCN guidelines - clinical, radiographic, or pathological (biopsy proven) T3 or higher, Gleason 8-10, PSA \> 20 ng/mL, the presence of intraductal, ductal, or cribriform features with any Gleason score, and can be N0 or N1
  * A month is defined as 28 days
* Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Subject must have the ability to understand and willingness to sign the written informed consent document.
* Age ≥18 at the time of consent
* ECOG Performance Status ≤ 2 (Appendix A)
* Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 3 months of registration.
* System Laboratory Value
* Hematological:

  * Platelet count (plt)1 ≥ 100,000/ µL
  * Hemoglobin (Hgb)1 ≥ 9 g/dL
  * Absolute neutrophil count (ANC) ≥ 1000 cells/µL
* Renal:

  --CrCl2 ≥ 45 mL/min
* Hepatic and Other:

  * Bilirubin3 ≤ 1.5 × upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) \< 2.5 × ULN
  * Alanine aminotransferase (ALT) \< 2.5 × ULN
  * Serum Albumin \> 3.0 g/dL
  * Serum potassium ≥ 3.5 mmol/L
* Coagulation:

  --International Normalized Ratio (INR) or Prothrombin Time (PT)
* Activated Partial Thromboplastin Time
* (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin)

  * Independent of transfusion and/or growth factors within 3 months prior to randomization
  * Cockcroft-Gault formula will be used to calculate creatinine clearance
  * In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin; if direct bilirubin is ≤1.5 × ULN, subject may be eligible
* 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.
* Ability to understand and comply with study procedures for the entire length of the study as determined by the site investigator or protocol designee
* Medications known to lower the seizure threshold (section 5.4.4) must be discontinued or substituted prior to C1D1 of study treatment for patients on Arm 2
* Able to swallow pills

Exclusion Criteria:

* Prior radical prostatectomy (excluding TURP and simple prostatectomy)
* History of any of the following:

  * Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign 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
* Known current evidence of any of the following:

  * Uncontrolled hypertension. Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy
  * Gastrointestinal disorder affecting absorption
  * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  * Known active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral DNA must be obtained in subjects with positive hepatitis B core antibody prior to first treatment start.
  * Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
  * Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular steroids or inhaled corticosteroids are permitted.
  * Any condition that, in the opinion of the site investigator, would preclude participation in this study
  * Baseline moderate or severe hepatic impairment (ChildPugh Class B or C)
* Patients who are currently receiving treatment with a prohibited medication according to Section 5.4 (Tables 2 and 3), must discontinue that medication prior to starting treatment and must not restart for the duration of the study if randomized to ARM 2.
* Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness or social situations that would limit compliance with study requirements
* Individuals with a history of another malignancy are not eligible if the cancer is under active treatment or the cancer can be seen on radiology scans or if they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years.