• Must have histologically confirmed prostate cancer.

• Age ≥ 18 years.

• ECOG performance status of 0-1.

• Must have the ability to understand and the willingness to sign a written informed consent document.

• Willing to provide serial blood samples for the study.

• Willing to provide tumor tissue (prostatectomy for primary cohort; prostatectomy or biopsy for exploratory cohort) for correlative studies which will compare ctDNA to tumor specimens.

• Primary Cohort: High-risk localized prostate adenocarcinoma defined as one or more of the following:

• o Clinical stage ≥ cT3a, Grade Group 4 or 5 (Gleason sum 8-10), and PSA ≥ 20

• \*Non-bulky pelvic lymphadenopathy and indeterminate findings on staging imaging (CT, bone scan, PSMA PET CT) are allowed if the surgeon believes RP is appropriate.

• Exploratory Cohort: Men with a diagnosis of prostate adenocarcinoma and one of the following:

‣ Localized prostate adenocarcinoma on active surveillance

⁃ Biochemically-recurrent prostate adenocarcinoma after definitive local therapy

⁃ Hormone-sensitive, metastatic prostate adenocarcinoma

⁃ Metastatic CRPC