This clinical trial evaluates whether positron emission tomography-magnetic resonance imaging (PET-MRI) using the radioactive drug radiohybrid prostate-specific membrane antigen (rhPSMA)-7.3 may help in detecting higher grade or stage disease in men with low and favorable intermediate risk prostate cancer who are candidates for active surveillance. A PET scan is a test that uses a radioactive drug and a computer to create images of how organs and tissues in the body are functioning. The radioactive drug used in this study, rhPSMA-7.3, attaches to the abnormal cells in the body at a different rate than normal cells which allows the scanner to create a detailed picture of how the body is working. An MRI scan uses strong magnets and computers to create detailed images of the soft tissue in your body. A multiparametric (mp)MRI is a type of MRI scan that creates a more detailed picture of the prostate gland. Using rhPSMA-73 with PET-MRI and mpMRI may be more effective in detecting higher grade or stage disease in men with low and favorable intermediate risk prostate cancer.

PRIMARY OBJECTIVE:

I. Measure the rate of rhPSMA-7.3-PET-MRI identified Gleason Grade Group (GG) 3-5 disease on pathology or locally advanced disease. A threshold rate of 15% detection will be considered clinically significant.

SEONDARY OBJECTIVE:

I. Assessment of safety.

EXPLORATORY OBJECTIVES:

I. Determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for rhPSMA-PET-MRI to detect prostate cancer in the prostate stratified by Gleason Grade Groups.

II. Correlate PET MRI findings with surgical specimens for those men who undergo surgical treatment (including assessment of pathological stage).

III. Define whether gene expression of PSMA (FOLH1) as defined on the Decipher messenger ribonucleic acid (mRNA) expression platform relates to signal intensity on PSMA scan.

IV. Determine whether Decipher genomic classifier scores, luminal / basal scores or androgen receptor activity scores relate to signal intensity on PSMA scans.

OUTLINE:

Patients receive rhPSMA-7.3 intravenously (IV) then undergo PET-MRI and mpMRI of the prostate on study. Patients also undergo Decipher test at screening and MRI-PET prostate biopsy or radical prostatectomy within 90 days per standard of care.

Inclusion Criteria:

• Healthy men (Eastern Cooperative Oncology Group [ECOG] 0-1), >= 18 years old with at least 10 year life expectancy
• Histologically proven Gleason Grade Group 1 or 2 adenocarcinoma of the prostate
• Last prostate cancer containing biopsy performed within 3-15 months (mo.) prior to screening. Biopsy must have been >= 10 core biopsy and informed by prior mpMRI
• Prostate cancer categorized as low risk or favorable risk by National Comprehensive Cancer Network (NCCN) criteria (low risk is defined as T1c-T2a, prostate-specific antigen [PSA] < 10ng/ml, Gleason Grade Group 1 [Gleason 3+3=6] disease) and favorable intermediate risk as having no more than one of the following intermediate risk features, clinical T2b-T2c disease, PSA 10-20ng/ml, Gleason Grade Group 2 [Gleason score 3+4=7])
• Decipher genomic classifier score from prior biopsy >= 0.45
• Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written informed consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures
• Concurrent diseases and malignancies are permitted
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on the study
• Willing to undergo prostate biopsy prior to non-surgical treatment of prostate cancer and within 90 days of PET-MRI imaging

Exclusion Criteria:

• Prior radiotherapy, surgery, chemotherapy, or hormonal therapy for prostate cancer
• NCCN very low risk category (T1c and Gleason Grade Group 1 [Gleason score 3+3=6], PSA < 10 ng/mL, fewer than 3 prostate biopsy cores positive, =< 50% cancer in any core, PSA density < 0.15 ng/mL/g)
• Decipher score < 0.45
• Prior bladder outlet procedure (i.e,. holmium laser enucleation of the prostate [HoLEP], transurethral resection of the prostate [TURP], Urolift, Rezum)
• Prohibited medications: use of 5 alpha reductase inhibitor or androgen deprivation therapy (i.e., leuprolide, relugolix) within 1 month of screening
• Contra-indication or relative contra-indication to MRI (i.e., pacemaker)
• History of hip replacement
• Subject has received investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening

A read will completed for the PET portion of the examination by a nuclear medicine trained radiologist who is blinded to the mpMRI portion of the exam.