Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)

Inclusion Criteria: * Histologically confirmed prostate cancer * PSA ≥ 0.1 after radical prostatectomy (value w/in 3 months of registration) AND at least 1 unfavorable risk factor listed below. * Gleason 8-10 * PSA \> 0.5 * Pathologically positive lymph nodes * pT3 or pT4 * PSA doubling time (DT) \< 10 months * Negative margins * Persistent PSA after RP (PSA never dropped below 0.1 after RP) * Local/regional recurrence on imaging * Decipher "High risk" (a Medicare-reimbursed test for risk of metastases after prostatectomy) * Candidate for salvage radiation and ADT treatment * 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. * 18 ≤ Age ≤ 95 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) ≥ 100,000/ µL * Hemoglobin (Hgb) ≥ 9 g/dL * Absolute neutrophil count (ANC) ≥ 1000 cells/µL * Renal: --GFR1 ≥ 45 mL/min * Hepatic and Other: * Bilirubin2 ≤ 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) * Cockcroft-Gault formula will be used to calculate creatinine clearance (see study procedure manual SPM) * 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 (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry (Section 5.5) * Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be discontinued prior to study entry * Able to swallow pills Exclusion Criteria: * Use of post-prostatectomy ADT for \> 30 continuous days prior to registration (ADT defined as use of GnRH agonist, with or without an anti-androgen). However, patients with testosterone recovery after post-prostatectomy ADT are eligible (testosterone recovery defined as total testosterone \> 190 ng/dL) regardless of how long they have been on ADT. * Prior pelvic radiation unless additional radiation can be safely delivered according to the treating physician * PSA \> 15 ng/mL in screening * 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 (e.g., 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 (e.g., human immunodeficiency virus \[HIV\] or viral hepatitis) * Any chronic medical condition requiring a dose of corticosteroid higher than 10 mg prednisone/prednisolone once daily * Any condition that, in the opinion of the site investigator, would preclude participation in this study * Moderate or severe hepatic impairment (Child Pugh Class B or C) * 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 * Confirmed bone metastases on imaging