Inclusion Criteria:

* Histologically confirmed high risk prostate adenocarcinoma
* Pathologic stages T1c-T4, N0-Nx-N1, M0-1 as staged by the pathology report (AJCC Criteria 8th Edition \[Ed\].)
* One or more high risk features including Gleason 8-10, T3-T4, prostate specific antigen (PSA) ≥ 20
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patients must sign institutional review board (IRB) approved study specific informed consent
* Patients must complete all required pre-entry tests
* Patients must be at least 18 years old
* Oligometastatic prostate cancer defined as disease in up to 5 distant or regional areas

Exclusion Criteria:

* Previous pelvic radiation
* Prior androgen suppression therapy for prostate cancer for more than 6 months
* Active rectal diverticulitis, Crohn's disease affecting the rectum or ulcerative colitis (non-active diverticulitis and Crohn's disease not affecting the rectum are allowed)
* Prior systemic chemotherapy for prostate cancer
* History of proximal urethral stricture requiring dilatation
* Current and continuing anticoagulation with warfarin sodium (Coumadin), heparin, low-molecular weight heparin, clopidogrel bisulfate (Plavix), or equivalent (unless it can be stopped to manage treatment related toxicity, to have a biopsy if needed, or place markers)
* Major medical, addictive or psychiatric illness which in the investigator's opinion, will prevent the consent process, completion of the treatment and/or interfere with follow-up. (Consent by legal authorized representative is not permitted for this study)
* Evidence of any other cancer within the past 5 years and \< 50% probability of a 5 year survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell cancer of the skin is allowed)
* History of myocardial infarction or decompensated congestive heart failure (CHF) within the last 6 months

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/04/2024. Questions regarding updates should be directed to the study team contact.