Hypofractionated Radiation Therapy or Conventional Radiation Therapy after Surgery in Treating Patients with Prostate Cancer

Inclusion Criteria

• 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) questionnaire
• Only English and French-speaking patients are eligible to participate as these are the only language the EPIC has been validated in
• PRIOR TO STEP 2 REGISTRATION
• The EPIC 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

Exclusion Criteria

• A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7 (Considered for NRG-GU002, principal investigator [PI]: Hurwitz)
• pT2 with a negative surgical margin and PSA < 0.1 ng/mL
• Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration; * Note: The use of finasteride or dutasteride (+/- tamsulosin) for longer periods prior to prostatectomy is acceptable
• Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for > 6 weeks (42 days)
• Neoadjuvant chemotherapy before or after prostatectomy
• Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed
• Previous chemotherapy for any other disease site if given within 3 years prior to step 1
• Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes
• Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 1 registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 1 registration * Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease * Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol * End-stage renal disease (ie, on dialysis or dialysis has been recommended)
• Prior allergic reaction to the study drugs involved in this protocol
• History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason