Castration-resistant prostate cancer patients with rising prostatic specific antigen (PSA) are eligible for this study. 11C-Choline PET/CT will be used to identify metastatic lesions. Patients with <=3 metastatic lesions will receive stereotactic body radiotherapy (SBRT) as definitive treatment. Blood draws will be taken to monitor the development of anti-prostate cancer immunity

Inclusion Criteria:

• Patients must be receiving standard of care SBRT as outlined in the Universal Content Management (UCM) Procedure Manual (http://mayocontent.mayo.edu/radoncology/categories/index.html)
• Age ≥ 18 years.
• Metastatic castration-refractory prostate cancer patients with ≤ 3 lesions identified on standard imaging and/or choline PET/CT within 60 days of registration
• Castrate levels of testosterone
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2 (Appendix I).
• Life expectancy > 6 months

Exclusion Criteria:

Emergent cord compression for spinal metastases

• Severe, active co-morbidity, defined as follows:

  1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
  2. Transmural myocardial infarction within the last 6 months prior to registration
  3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
  5. Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease.
  6. HIV positive with Cluster Differentiation 4 (CD4) count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
  7. End-stage renal disease (i.e., on dialysis or dialysis has been recommended).

• Metastases located within 3 cm of the previously irradiated structures:

  1. Spinal cord previously irradiated to > 40 Gy
  2. Brachial plexus previously irradiated to > 50 Gy
  3. Small intestine, large intestine, or stomach previously irradiated to > 45 Gy
  4. Brainstem previously irradiated to > 50 Gy
  5. Lung previously irradiated with prior V20Gy > 30%

Patients must be receiving standard of care SBRT