In this study, participants will have standard Androgen Deprivation Therapy and undergo standard external beam radiation therapy to the prostate and at-risk lymph nodes by Intensity Modulated Radiation Therapy. The subsequent *boost* radiation therapy to the prostate alone will be given using the CyberKnife, rather than using the standard Intensity Modulated Radiation Therapy. This study will also see how CyberKnife affects the quality of the participant's life.

In this study, participants will have standard androgen deprivation therapy and undergo standard radiation therapy to the prostate and at-risk lymph nodes by intensity-modulated radiation therapy (IMRT). The subsequent *boost* radiation therapy to the prostate alone will be given using the CyberKnife, rather than using the standard Intensity Modulated Radiation Therapy. This study will also see how CyberKnife affects the quality of the participant's life.

Inclusion Criteria:

1. Histologically proven adenocarcinoma of the prostate

   1. Gleason score (2-10)
   2. Biopsy within six months of date of registration
   3. Patient age >18 years

2. Clinical stage (American Joint Committee on Cancer 7th Edition)

   a. T-stage determined by physical exam (Digital Rectal Exam Required)

   i. MRI findings (e.g. extracapsular extension) can be used to determine T-staging

   b. N-stage determined using abdominopelvic CT scan and/or MRI

   c. M-stage determined by physical exam, CT and/or MRI, and bone scan (must be M0, excepting Lymph nodes)

   Please note: a SPECT bone scan including a CT of the abdomen and pelvis or an F18 Fluciclovine PET/CT fulfills protocol criteria for both the abdominopelvic CT and bone scan.

3. Patients must belong to one of the following risk groups:

   • PSA > 20 and < 150 and/or
   • Gleason 8-10 and/or
   • > clinical T3a and/or
   • Clinical N1

   OR

   • PSA 10 - 20 AND
   • Gleason 7 AND
   • Clinical T2b - T2c

4. Patient is receiving, or planning to receive standard androgen deprivation therapy and initial IMRT to the prostate and positive or at-risk lymph nodes.

5. Prostate volume greater than 20 cc and less than 100 cc

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

7. Patient has agreed to complete questionnaires

8. Signed IRB approved informed consent

9. Patient eligible to have an MRI

10. Must be able to tolerate the confinement of an MRI procedure

Exclusion Criteria:

1. No prior prostate surgery (including TURP) or prostate cancer treatment with the exception of androgen deprivation therapy
2. No prior radiotherapy to the pelvis
3. No implanted hardware (including metal) or other material that would prohibit appropriate treatment planning or treatment delivery
4. No metastatic disease, with the exception of lymph node positive disease
5. No chemotherapy for a malignancy in the last 5 years.
6. No history of an invasive malignancy (other than basal or squamous skin cancers) in the last 5 years.
7. No heart pacemaker, No metallic foreign body (metal sliver) in the eye, No aneurysm clip in the brain
8. No history of a pelvic or horseshoe kidney
9. No diagnosis of inflammatory bowel disease