PROSTATE-IQ: Parallel RandOmized STudy of Personalized Apalutamide Treatment and Evaluation to Improve Quality of Life in Post-Operative Radiation With Androgen Axis Suppression. A Phase III Multi-center Study for Men With Detectable PSA After Prostatectomy for Prostate Cancer.

Inclusion Criteria:

1. Histologically confirmed prostate cancer.

2. PSA ≥ 0.1 after radical prostatectomy.

3. Candidate for salvage radiation and ADT treatment, as determined by treatingphysician.

4. Age >18 at the time of consent.

5. ECOG Performance Status ≤ 2.

6. Demonstrate adequate organ function as defined in the table below. All screeninglabs to be obtained within 90 days of registration. System Laboratory Value Hematological: Platelet count (plt) = ≥ 100,000/µL Hemoglobin (Hgb) = ≥ 9 g/dL Renal: eGFR = ≥ 30 mL/min using MDRD Formula Hepatic and Other: Bilirubin2 = ≤1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) = ≤ 2.5 x ULN Alanine aminotransferase (ALT) = ≤ 2.5 x ULN Serum Albumin = > 3.0 g/dLSerum potassium = ≥ 3.5 mmol/L 2In subjects with Gilbert's syndrome, if totalbilirubin is >1.5 x ULN, measure direct and indirect bilirubin; if direct bilirubinis ≤ 1.5 x ULN, subject may be eligible.

7. Ability to understand and comply with study procedures for the entire length of thestudy as determined by the site investigator or protocol designee.

8. Ability to understand English or Spanish language as determined by the siteinvestigator or protocol designee. Since the primary outcome is a questionnaireavailable in English and Spanish.

9. Written informed consent and HIPAA authorization for release of personal healthinformation prior to registration. NOTE: HIPAA authorization may be included in theinformed consent or obtained separately. Participants must have the ability tounderstand and willingness to sign the written informed consent document.

Exclusion Criteria:

1. Use of post-prostatectomy testosterone suppression prior to registration (use ofGnRH agonist or antagonist, with or without an anti-androgen). However, participantswith testosterone recovery after post-prostatectomy testosterone suppression areeligible (testosterone recovery defined as total testosterone > 190 ng/dL)regardless of how long their testosterone was suppressed.

2. History of any of the following:

• Seizure or known condition that may pre-dispose to seizure (e.g. prior strokewithin 1 year prior to randomization, brain arteriovenous malformation,Schwannoma, meningioma, or other benign CNS or meningeal disease which mayrequire treatment with surgery or radiation therapy).

• Severe or unstable angina, myocardial infarction, symptomatic congestive heartfailure, arterial or venous thromboembolic events (eg, pulmonary embolism,cerebrovascular accident including transient ischemic attacks), or clinicallysignificant ventricular arrhythmias within 6 months prior to randomization. Anycondition that in the opinion of the investigator, would preclude participationin this study.

3. Current evidence of any of the following:

• Uncontrolled hypertension (consistently >160 systolic or >100 diastolic)

• Gastrointestinal disorder affecting absorption

• Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis).

• Any condition that in the opinion of the investigator, would precludeparticipation in this study.

4. Participants with a prior or concurrent malignancy whose natural history ortreatment does not have the potential to interfere with the safety or efficacyassessment of the investigational regimen are eligible for this trial.

5. Confirmed extrapelvic or bone disease

6. Medications known to lower the seizure threshold (listed in section 5 below) must bediscontinued or substituted 4 weeks prior to C1D1 of study treatment forparticipants on arms receiving apalutamide.