Radiation Therapy With or Without Apalutamide in Treating Patients With Recurrent Prostate Cancer, the BALANCE Trial

Inclusion Criteria

• •Pathologically (histologically) proven diagnosis of prostate adenocarcinoma; prostatectomy must have been performed within 10 years prior to Step 1 registration and any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
• •Post-prostatectomy patients with a detectable serum PSA (\>= 0.1, but =\< 1.0 ng/mL) at study entry (within 90 days of Step 1 registration) and at least one of the following:
• •* Gleason score 7-10 (International Society of Urological Pathology \[ISUP\] grade group 2 to 5)
• •* ISUP grade group:
• •* Grade group 1 = Gleason score =\< 6,
• •* Grade group 2 = Gleason score 3 + 4 = 7,
• •* Grade group 3 = Gleason score 4 + 3 = 7,
• •* Grade group 4 = Gleason score 8,
• •* Grade group 5 = Gleason scores 9 and 10
• •* \>= T3a disease
• •* Persistent elevation of PSA after prostatectomy measured within 90 days after surgery (PSA never became undetectable) of \> 0.04 but \< 0.2 ng/mL (PSA nadir)
• •pN0 or pNx
• •History/physical examination within 90 days prior to Step 1 registration
• •Karnofsky performance status of 70-100 within 90 days prior to Step 1 registration
• •Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on Decipher GRID platform; Note: if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation and for GenomeDx to provide the subtyping needed for stratification
• •Prior androgen deprivation therapy (luteinizing hormone-releasing hormone \[LHRH\] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to Step 1 registration and given for =\< 90 days duration
• •* For example: patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date
• •* Please note: finasteride or dutasteride must be stopped before treatment starts but prior usage will not affect eligibility
• •Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors within 90 days prior to Step 1 registration
• •Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors within 90 days prior to Step 1 registration
• •Serum albumin \>= 3.0 g/dL within 90 days prior to Step 1 registration
• •Glomerular filtration rate (GFR) \>= 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine within 90 days prior to Step 1 registration
• •Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) (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 is eligible) within 90 days prior to Step 1 registration
• •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5 x ULN within 90 days prior to Step 1 registration
• •Testosterone \> 50 ng/dL within 90 days prior to Step 1 registration
• •Concomitant medications known to lower the seizure threshold discontinued or substituted at least 4 weeks (30 days) prior to Step 1 registration
• •The patient must agree 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 agree 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
• •The patient must agree not to donate sperm during the study treatment and for 3 months after receiving the last dose of study drug
• •The patient or a legally authorized representative must provide study-specific informed consent prior to study entry