A Randomized Phase III Trial of Hypofractionated Post-prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-prostatectomy Radiation Therapy (COPORT)

• PRIOR TO STEP 1 REGISTRATION

• Adenocarcinoma of the prostate treated primarily with radical prostatectomy

‣ Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy

• One of the following pathologic T-classifications: pT2 or pT3

‣ Patients with positive surgical margins are eligible

• One of the following pathologic N-classifications: pN0, pNX

‣ If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus (vs.) extended lymph node dissection) should be noted whenever possible

• No clinical evidence of regional lymph node metastasis

‣ Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration

⁃ Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =\< 1 cm in the short axis

• A post-radical prostatectomy study entry PSA \>= 45 days after prostatectomy and within 30 days prior to step 1, \< 2.0 ng/mL

• No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration

‣ Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass

⁃ Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor

• No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration

‣ Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis

• Zubrod performance status 0-1 within 60 days prior to step 1 registration

• The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration

• Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire

• Only English and French-speaking patients are eligible to participate

• PRIOR TO STEP 2 REGISTRATION

• The EPIC-26 must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization