A Study to Evaluate Hypofractionated Proton Therapy or IMRT for Recurrent, Oligometastatic Prostate Cancer

This phase II trial studies the side effects of radiation therapy (hypofractionated proton beam therapy or IMRT) for the treatment of prostate cancer that has come back (recurrent) or that has spread to a limited number of sites (oligometastatic) following primary localized treatment. Hypofractionated proton beam radiation therapy delivers smaller doses of radiation therapy over time and may kill more tumor cells and have fewer side effects. IMRT uses high energy x-rays to kill tumor cells and shrink tumors. This trial is being done to find out if a shorter course of radiation therapy is better with fewer side effects for patients with recurrent prostate cancer.

PRIMARY OBJECTIVE:

I. To assess late \>= grade 3 gastrointestinal (GI) and/or genitourinary (GU) toxicity of interest with the hypofractionated regimen with proton beam therapy or intensity-modulated radiation therapy (IMRT) (late defined as 3 to 24 months after protocol radiation therapy \[RT\]).

SECONDARY OBJECTIVES:

I. Late grade \>= 2 GI and/or GU toxicities of interest within 24 months after the protocol RT, using the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0.

II. Acute grade \>= 3 GI and/or GU toxicities of interest during and within 3 months after the protocol RT, using the CTCAE v4.0.

III. Compare the rates of late \>= grade 3 GI and/or GU toxicity between the 2 treatment schedules.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo proton beam radiation therapy 5 days a week over 3 weeks. Patients undergo positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood sample collection throughout the study.

ARM II: Patients undergo IMRT 5 days a week over 5 weeks. Patients undergo PET scan, CT scan, MRI, and blood sample collection throughout the study.

After completion of study, patients are followed up at 3-6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months.

Eligibility Criteria:
Inclusion Criteria:

* Male; age \>= 18 years
* Histological confirmation of prostate adenocarcinoma
* Recurrent prostate cancer after prior receipt of primary radiotherapy to the prostate (can also include treatment of splenic vessels \[SVs\] and lymph nodes \[LNs\]) or salvage RT to the prostate fossa (can also include prior pelvic RT)
* Oligometastatic extent of disease

  * Recurrent disease involving lymph nodes as diagnosed with choline positron emission tomography (PET)/computed tomography (CT) or other advanced PET imaging (prostate-specific membrane antigen \[PSMA\] or flucyclovine)
  * Limited to pelvic and/or retroperitoneal/para-aortic lymph nodes
* Zubrod performance score (PS) =\< 1
* Signed informed consent

Exclusion Criteria:

* Bone or visceral metastases present
* Lymph node metastases beyond the pelvis and/or retroperitoneum
* Contraindications to RT (e.g., uncontrolled inflammatory bowel disease)
* Contraindications to androgen suppression
* Concurrent antineoplastic agents (chemotherapy)
* Previous or concurrent malignancy other than non-melanoma skin cancer within 5 years of diagnosis of prostate cancer
* Inability to start the radiation portion of the protocol treatment within 6 months after study enrollment
* Medical or psychiatric conditions that preclude informed decision-making or compliance with the protocol treatment or follow-up