Androgen Receptor Signaling and Prostate-Specific Membrane Antigen Expression

Inclusion Criteria:

• Patients age 40 or higher with prostate cancer that has been previously treated withprimary definitive local therapies (prostatectomy with or without salvage radiation,or primary prostate radiation) and subsequently experiencing rising PSA meetingcriteria for biochemical failure (PSA >0.2 ng/dL x2 following prostatectomy, or PSA > 2 + nadir value following primary radiation).

• PSMA PET/CT (Ga68, piflutolastat F-18, or other FDA-approved tracer) during time ofbiochemical recurrence, and within 6 weeks of registration, showing at least onelesion suspicious for recurrent prostate cancer based on size and/or SUV.

• Testosterone >100 ng/dL within 6 months prior to enrollment with no interveninghormonal therapies.

• Assigned by treating physician to receive standard-of-care AR antagonistmonotherapy, using FDA-approved apalutamide, darolutamide, or enzalutamide.

Exclusion Criteria:

• High disease burden, significant symptoms of disease, or other clinical situationrequiring medical/surgical castration and/or docetaxel during the time of the study.

• Not suitable for AR antagonist therapy (e.g. inability to swallow pills, pooradherence, advanced liver disease, prohibitive co-payment without available patientassistance funding, contraindicated drug-drug interaction).

• Older-generation AR antagonists (e.g. bicalutamide) are not allowed on study.