Sipuleucel-T With or Without Radiation Therapy in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer

This randomized phase II trial studies how well giving sipuleucel-T with or without radiation therapy works in treating patients with hormone-resistant metastatic prostate cancer. Vaccines may help the body build an effective immune response to kill tumor cells. Radiation therapy uses high energy x rays to kill tumor cells. It is not yet known whether giving sipuleucel-T vaccine is more effective with or without radiation therapy in treating prostate cancer

Inclusion Criteria: * Histologically documented adenocarcinoma of the prostate * Life expectancy of \>= 6 months, Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen or pelvis * Castration resistant prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression despite castrated level of testosterone (\< 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy; disease progression has to be demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below: * PSA: Two consecutive rising PSA values, at least 7 days apart * Measurable disease: \>= 20% increase in the sum of the longest diameters of all measurable lesions or the development of any new lesions; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response * Non-measurable disease: * Soft tissue disease: The appearance of 1 or more lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response * Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression * White blood cell (WBC) \>= 2,500 cells/uL * Absolute neutrophil count (ANC) \>= 1,000 cells/uL * Platelet count \>= 75,000 cells/uL * Hemoglobin (HgB) \>= 9.0 g/dL * Creatinine =\< 2.5 mg/dL * Total bilirubin =\< 2 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT, serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN * Prior chemotherapy with 0-2 regimens is allowed * Prior radiation therapy to prostate or prostate bed is allowed provided it occurred \> 3 months before enrollment to the study Exclusion Criteria: * The presence of liver, or known brain metastases, malignant pleural effusions, or malignant ascites * Moderate or severe symptomatic metastatic disease, defined as a requirement for treatment with opioid analgesics for cancer-related pain within 21 days prior to registration * Eastern Cooperative Oncology Group (ECOG) performance status \> 2 * Treatment with chemotherapy within 3 months of registration * Treatment with any of the following medications or interventions within 28 days of registration: * Systematic corticosteroids; use of inhaled, intranasal, and topical steroids is acceptable * Any other systemic therapy for prostate cancer (except for medical castration) * History of external beam radiation therapy to metastatic sites within 1 year of enrollment to the study * Participation in any previous study involving sipuleucel-T * Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography \> 50%) or spinal cord compression * Concurrent other malignancy with the exception of: * Cutaneous squamous cell and basal carcinomas * Adequately treated stage 1-2 malignancy * Adequately treated stage 3-4 malignancy that has been in remission for \>= 2 years at the time of registration * A requirement for systemic immunosuppressive therapy for any reason * Any infection requiring parenteral antibiotic therapy or causing fever (temperature \> 100.5 degrees Fahrenheit \[F\] or 38.1 degrees Celsius \[C\]) within 1 week prior to registration * Any medical intervention or other condition which, in the opinion of the principal investigator could compromise adherence with study requirements or otherwise compromise the study's objectives