3.1.7. Prior radiation therapy to prostate or prostate bed is allowed provided it occurred > 3 months before enrollment to the study. 3.2 Exclusion Criteria 3.2.1 The presence of liver, or known brain metastases, malignant pleural effusions, or malignant ascites. 3.2.2 Moderate or severe symptomatic metastatic disease defined as a requirement for treatment with opi oid analgesics for cancer-related pain within 21 days prior to registration. 3.2.3 Eastern Cooperative Oncology Group (ECOG) performance status > 2 (see Appendix 1). 3.2.4 Treatment with chemotherapy within 3 months of registration. 3.2.5 Treatment with any of the following medications or interventions within 28 days of registration:  Systemic corticosteroids. Use of inhaled, intranasal, and topical steroids is acceptable.  Any other systemic therapy for prostate cancer (except for medical castration). 3.2.6 History of external beam radiation therapy to metastatic sites within 1 year of enrollment to the study. 3.2.7 Participation in any previous study involving sipuleucel-T. 3.2.8 Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression. 3.2.9 Concurrent other malignancy with the exception of: a) cutaneous squamous cell and basal carcinomas, b) adequately treated stage 1-2 malignancy , c) adequately treated stage 3-4 malignancy that has been in remission for ≥ 2 years at the time of registration. 3.2.10 A requirement for systemic immunosuppressive therapy for any reason. 3.2.11 Any infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5°F or 38.1°C) within 1 week prior to registration. 3.2.12 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. 3.3 Inclusion of Women and Minorities Prostate cancer is exclusively disease of men. The study is open anyone regardless of race and ethnicity. Efforts will be made to extend the accrual to a representative population, but in a trial which will accrue approximately 50 subjects, a balance must be struck between subject safety considerations and limitations on the number of individuals exposed to potentially toxic or ineffective treatments on the one hand and the need to explore racial, and ethnic aspects of clinical research on the other. If differences in outcome that correlate to racial or ethnic identity are noted, accrual may be expanded or additional studies may be performed to investigate those differences more fully. Page 16 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 4.0 Screening and Registration Procedures 4.1 Screening Procedures Diagnostic or laboratory studies performed exclusively to determine eligibility for this trial will be done only after obtaining written informed consent. Studies or procedures that were for clinical indications (not exclusively to determine study eligibility) may be used for baseline values, even if the studies were done before informed consent was obtained. Reference is made to Section 10.0 – Study Calendar. 4.2 Informed Consent The investigational nature and objectives of the trial, the procedures and treatments involved and their attendant risks and discomforts, and potential alternative therapies will be carefully explained to the subject and a signed informed consent will be obtained. Documentation of informed consent for screening will be maintained in the subject’s research chart and medical record. 4.3 Registration Requirements/Process Registration Process To register a patient, the treating physician should contact the protocol nurse or the responsible Clinical Research Associate (CRA) in Clinical Trial Office (CTO) to complete the eligibility/registration form. The protocol nurse or CRA will contact the Data Coordinating Center at the City of Hope (626-256-4673, ext. 64267 or e-mail dcc@coh.org), EMAIL a copy of the completed eligibility checklist, required pre-study tests (per protocol – and may include laboratory, CT and pathology reports), signed Informed Consent, signed Patients' Bill of Rights and HIPAA authorization form to dcc@coh.org. The patient registration process will be handled by the Department of Clinical Research Information Support (CRIS) Data Coordinating Center (DCC) at City of Hope. Documentation of current IRB approval must be on file with the DCC prior to registration of patients on this study for participating institution. The steps below are to be taken when registering a patient:  The research staff must assure they have the most current and updated version of the protocol and informed consent prior to enrolling a patient. If a question arises, please contact the Data Coordinating Center at 626-256-4673 extension 64267 or via email at dcc@coh.org.  The study staff must assure that all prestudy laboratory tests, scans and x-rays have been completed prior to registration according to the study calendar  The study staff must assure that the patient has signed an approved informed consent prior to registration/randomization, including the Experimental Subject Bill of Rights and appropriate HIPAA authorization.  The study staff must confirm that the patient meets all inclusion and exclusion eligibility criteria for the protocol. The eligibility checklist (provided by the COH DCC) must be completed in its entirety.  Patients must be registered prior to initiation of treatment but no more than 2 weeks prio r to planned start of treatment. A patient failing to meet all protocol requirements may not be registered.  Once a patient is eligible, all the pre-study requirements have been fulfilled, and the informed consent obtained, the research nurse or the data manager (study coordinator) will inform the Page 17 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 C OH Data Coordinating Center at (626) 256-4673, extension 64267; email dcc@coh.org and FAX (fax number 626 256-8794) a copy of the patient’s signed informed consent, , completed eligibility checklist and corresponding source documentation confirming eligibility (including pathology reports, lab reports, x-ray reports, etc.). The City of Hope Data Coordinating Center will:  Review all materials/source documentation to ensure the patient is eligible.  Ensure the consent form is valid and is signed correctly by all parties. If additional information is needed or should there be any questions, the Data Coordinating Center will immediately contact the participating institution and registration will not occur until all issues are resolved.  If there are questions regarding exceptions to the eligibility criteria, please contact he study Principal Investigator, as well as the COH DCC. Documentation of IRB approval of exception will need to be submitted as well as the COH DCC.  The patient will be registered and randomized centrally at City of Hope.  Confirmation of Registration/Randomization will be emailed/faxed to the study staff noting the p atient’s study number as well as assigning the randomization arm within 24 hours post receipt of a complete eligibility packet.  The COH DCC will call the research nurse or data manager (study coordinator) and verbally confirm the registration (if needed).  If the patient does not receive protocol therapy following registration, the patient’s registration on the study may be cancelled. The COH DCC should be notified of cancellations as soon as possible.  The COH DCC will log into the Electronic Data Capture (EDC) system and enter the patient’s study numbe r. 4.4 Randomization Randomization will be performed by the Department of Biostatistics 5.0 Treatment Program 5.1 Treatment Overview Treatment will be performed on an outpatient basis. Patients randomized to Arm A will we treated with standard Sipuleucel - T. Leukapheresis will be performed at the contracted, designated Dendreon facility and Sipuleucel-T infusion will be performed at the City of Hope infusion clinic approximately 72 hours after leukapheresis. This process will be repeated every 2 weeks times three. Patients randomized to Arm B will undergo 2 weeks of radiation therapy to single metastatic site followed by 7 days of rest followed by treatment with Sipuleucel- T on an identical schedule as Arm A (see study schema) Delays in leukapheresis of up to 2 weeks for each cycle are acceptable regardless of cause. Page 18 of 50 IRB Protocol No.