This phase I trial studies stereotactic body radiation therapy (SBRT) in treating patients with prostate cancer that is likely to come back or spread (high-risk) undergoing surgery. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Delivering radiotherapy before prostatectomy by SBRT is more convenient, conformal, and may spare normal tissues better than delivering radiotherapy after prostatectomy.

PRIMARY OBJECTIVES:

I. To assess feasibility of pre-operative stereotactic body radiotherapy (SBRT) in prostate cancer patients at high risk for recurrence after prostatectomy.

SECONDARY OBJECTIVES:

I. To assess safety and acute toxicity of SBRT followed by prostatectomy. This will be based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and patient reported quality of life (Expanded Prostate Cancer Index Composite [EPIC] and International Prostate Symptom Score [IPSS] questionnaires).

II. Investigation of the radiobiology of SBRT in prostate cancer using resected prostate tumor tissue.

III. Evaluation of the nature of the immune response to prostate cancer generated by SBRT.

OUTLINE:

Patients undergo 3 fractions of SBRT over 1-2 weeks, 2-4 weeks prior to radical prostatectomy.

After completion of the study treatment, patients are followed up at 0 to 4 weeks, and every 3 months for 1 year.

Inclusion Criteria:

• Histologically confirmed primary non-metastatic adenocarcinoma of the prostate

• Patient desires and is medically fit to undergo prostatectomy

• Karnofsky performance status (KPS) >= 70

• Patients on androgen deprivation therapy (ADT) are allowed

• For confirmation of high risk local failure status, patients will have any one of the following:

  • Computed tomography (CT) or magnetic resonance imaging (MRI) demonstrating seminal vesicle invasion (SVI) or extraprostatic extension (EPE) within 1 year of enrollment into the study
  • Pre-biopsy prostate-specific antigen (PSA) >= 20
  • Gleason score 7-10 (Gleason 7 must be 4+3), presence of any Gleason 5 (even if a tertiary score) as determined at diagnostic biopsy
  • Gleason score 7 and > 50% of biopsy cores positive for prostate cancer
  • Clinical stage >= T3 (staging by imaging acceptable)

• An image-guided biopsy (via Artemis Ultrasound with MRI co-registration) is encouraged but not required if not performed as standard of care biopsy

Exclusion Criteria:

• Distant metastases, based upon:

  • CT scan or MRI of the abdomen/pelvis or prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) within 120 days prior to registration and
  • Bone scan or PSMA PET/CT within 120 days prior to registration; if the bone scan is suspicious, a plain x-ray and/or MRI must be obtained to rule out metastasis prior to registration

• Patient is unable or unwilling to sign consent

• Patient is considered low-risk and would not have received adjuvant radiation therapy (RT) outside of this study