History of histologically confirmed, clinical localized adenocarcinoma of the prostate treated with radical prostatectomy with definitive intent

Presence of any ONE of the following: * Adverse pathologic features at the time of prostatectomy (positive surgical margin, pathologic T-stage 3-4 disease, pathologic Gleason score 8-10 disease, OR presence of tertiary Gleason grade 5 disease) * Documentation of rising prostate-specific antigen on at least two consecutive draws, with the magnitude of prostate-specific antigen exceeding 0.03 ng/mL * Intermediate- or high-risk Decipher genomic classifier score * Identification of prostate cancer in \>= 1 lymph node at the time of prostatectomy (pN+ disease)

CT scan and MRI of the pelvis within 120 days prior to enrollment \[note: (a) if patient has medical contraindication to MRI, an exemption will be granted and enrollment can proceed; (b) for patients with PSA \< 1.0 ng/mL, the treatment planning CT can substitute for a diagnostic CT scan; (c) a low-field, radiation planning MRI can replace the diagnostic MRI if the patient refuses or cannot obtain a high-field MRI\]

Bone scan OR advanced nuclear imaging study within 120 days prior to enrollment for patients with PSA \> 1.0 ng/mL

Age \>= 18

Karnofsky performance status (KPS) \>= 70 and/or Eastern Cooperative Oncology Group (ECOG) =\< 2

Ability to understand, and willingness to sign, the written informed consent

Patients with any evidence of distant metastases. Note, evidence of lymphadenopathy below the level of the renal arteries can be deemed loco regional per the discretion of the investigator

Patients with neuroendocrine or small cell carcinoma of the prostate

Prior pelvic radiotherapy

History of Crohn's disease, ulcerative colitis, or ataxia telangiectasia