In this study, prostate cancer patients whose cancer has not spread to the lymph nodes will receive radiation therapy targeted to the prostate and nearby tissues with or without whole pelvis radiation therapy. PSMA imaging will be used to visualize prostate cancer prior to starting the trial.

The current treatment of high risk and very high risk localized prostate cancer is by radiation therapy (RT) and hormone therapy (ADT). RT uses radiation to kill the cancer cells while hormone therapy lowers the levels of male hormones like testosterone, which the cancer needs to grow. Radiation is targeted to the prostate and nearby tissues, which may or may not include whole pelvis radiation therapy (WPRT). The benefit of whole pelvis radiation therapy is not well understood. Therefore, clinical research is needed to assess the benefits/risks of whole pelvis radiation therapy in prostate cancer treatment. In addition to traditional cancer imaging methods like CT, MRI, and bone scan, new techniques like PSMA imaging are now available to examine prostate cancer. The PSMA scan involves a small amount of radioactive tracer (18F-PSMA-1007) being injected into the vein, which marks the prostate cancer cells for better visualization of the cancer location and spread. Because of its higher accuracy, results of PSMA scans can change how doctors plan cancer treatment, like where they aim radiation and how much they use.

In this study, prostate cancer patients whose cancer has not spread to the lymph nodes will receive radiation therapy. PSMA imaging will be used to visualize prostate cancer prior to starting the trial.

There will be two treatment groups (1) Prostate Only Radiation Therapy (PORT), and Prostate + Whole Pelvis Radiation Therapy (P-WPRT), and all participants will receive hormone therapy as part of standard of care. In addition to comparing the biochemical failure free survival (BFFS) between the two treatment groups, the study will also compare distant metastases free survival (DMFS), toxicity, patient reported outcomes and overall survival (OS).

Inclusion Criteria:

PSMA-N0M0 patients who have a documented history of High Risk localized adenocarcinoma of the prostate are eligible to participate if they meet the following eligibility criteria:

1. Participants capable of giving written informed consent.
2. Male.
3. Age ≥18 years.
4. ECOG ≤2.
5. Patient has histologically proven adenocarcinoma of prostate gland with an assigned Gleason score and Gleason Grade Group.
6. ≥NCCN High-Risk localized disease as per standard imaging investigations including pelvic imaging (CT, MRI) and 99Tc bone scan. High Risk prostate cancer defined as any of the following: cT3-T4 disease OR PSA ≥20 ng/ml OR Gleason grade group 4 or 5.
7. No documentation of regional nodal (N1) or metastatic (M1) prostate cancer on standard imaging (CT, MRI, or 99Tc bone scan).
8. In the opinion of the treating oncologist, patient is fit to undergo radical external beam radiotherapy to the prostate.
9. Patient commits to androgen suppression treatment as per standard of care. 10. Patient is willing to complete symptom and patient reported outcome questionnaires.

11. Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 6 months after the last dose of radiation therapy. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.

Male patients should agree to not donate sperm during the study and for 6 months after completion of radiation therapy.

Exclusion Criteria:

1. Inability to complete the investigational imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.).
2. Any additional medical condition, serious inter-current illness or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study performance, interpretation, or compliance with radiation
3. Patients who have initiated therapy (ADT, systemic therapy, or radiation) for their prostate cancer prior to PSMA-PET imaging.
4. History of inflammatory bowel disease, anal stenosis, colorectal surgery, or repeated endoscopic examinations/interventions related to anorectal diseases.
5. History of prostatectomy or previous pelvic radiotherapy.
6. Previous malignancy within the last five years, except BCC or SCC skin or a malignancy treated curatively with no evidence of disease for ≥5 years.
7. Bilateral hip prostheses will be ineligible for study