MDRT in Prostate Cancer Treated With Long-term Androgen Deprivation Therapy in the STAMPEDE Trial (METANOVA)

Inclusion Criteria:

• Participant must be ≥ 18 years of age.

• Participant must have an ECOG performance status ≤ 1.

• Histologic confirmation of prostate adenocarcinoma of the prostate gland, withevidence of metastasis on imaging by conventional imaging (MRI, CT, or 99mTc bonescan) or PSMA PET/CT. Biopsy of sites of metastasis is strongly encouraged, but notrequired.

• There must be at least 10-15 unstained slides from 2 cores of the highest tumorcellularity available.

• Newly diagnosed disease with no prior treatment(surgery, radiation or systemictreatment, ie hormone therapy or chemotherapy) to the primary disease.

• Participants may have started LHRH agonist or antagonist therapy, alone as longas it was not started more than 30 days before the participant is enrolled onthis study.

• In participants who undergo only conventional imaging, oligometastatic disease isdefined as 1-5 discrete metastatic sites in the bone and/or extra-pelvic lymph node (LN) stations.

• Extra-pelvic LN stations are superior to the regional/pelvic LN stations.Pelvic LN stations commence at the bifurcation of the aorta and bifurcation ofthe proximal inferior vena cava to the common iliac veins.

• Radiographic criteria for a LN to be considered a metastatic focus isdefined as short-axis diameter in the axial plane of ≥ 1.0 cm, withirregular border and/or heterogeneous morphology

• In participants who undergo PSMA PET/CT (in the presence or absence of conventionalimaging), oligometastatic disease is defined as 1-10 PSMA avid bone lesions and/orextra-pelvic LN stations. The MI-RADS reporting system will be followed to guidePSMA PET interpretation

• In participants extra-pelvic nodal (M1a) disease only by PSMA PET/CT and M0 byconventional imaging (i.e. extra-pelvic LN did not meet size criteria by CT),participant must meet 2 of 3 following criteria in order to be eligible:

1. PSA ≥ 40

2. Evidence of cN1 disease (pelvic LN)

3. Decipher score ≥ 0.89

• Adequate organ and marrow function to receive treatment per treating physician

• Medically fit for treatment and agreeable to follow-up.

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

Participants with the presence of any of the following:

• Castration resistant prostate cancer (CRPC).

• Evidence of visceral or intracranial metastases.

• Participant receiving any other investigational agents for cancer.

• Participant is participating in a concurrent treatment protocol for cancer.

• Unable to lie flat during or tolerate PET/MRI, PET/CT or SBRT.

• Prior definitive treatment to the primary prostate cancer or pelvis.

• Participant with uncontrolled intercurrent illness including, but not limited toongoing or active infection, symptomatic congestive heart failure, unstable anginapectoris, cardiac arrhythmia, uncontrolled diabetes (HgA1c > 10), active pituitaryor adrenal dysfunction, or psychiatric illness/social situations that would limitcompliance with study requirements

• History of another active malignancy within the previous 2 years, except fornon-melanoma skin cancer, non-muscle invasive bladder cancer, or a malignancy thatis considered cured with minimal risk of recurrence

• Active Crohn's disease or ulcerative colitis despite medical management.

• Refusal to sign informed consent.

• Any condition that in the opinion of the investigator would preclude participationin this study