Extremely Hypofractionated Intensity Modulated Stereotactic Body Radiotherapy for the Treatment of Prostate Cancer With Rising PSA After Radical Prostatectomy

Eligibility Criteria

• * 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