The purpose of this prospective cohort study is to investigate the role of Fluciclovine Positron Emission Tomography (PET) in patients with biochemical recurrence of prostate cancer (BCR) and a negative Prostate Specific Membrane Antigen (PSMA) PET, specifically, whether Fluciclovine PET can help detect local recurrence and whether the results of Fluciclovine PET can change management.

PRIMARY OBJECTIVE:

I. To evaluate the detection rate of local recurrence of prostate cancer on Fluciclovine PET in patients with BCR and a negative or equivocal PSMA PET obtained within 30 days prior to the Fluciclovine PET.

SECONDARY OBJECTIVES:

I. To evaluate the correct localization rate of Fluciclovine PET in patients with positive scans.

II. To distinguish the detection rate by site of recurrence (local recurrence in the prostate bed, lymph node involvement, or distant metastatic disease), and stratify by PSA level at the time of the scan and tumor grade

III. To evaluate the change in management based on the results of Fluciclovine PET, relative to intended management based on the result of negative PSMA PET alone, prior to obtaining the Fluciclovine PET.

OUTLINE:

Patients will be imaged with Fluciclovine PET within 30 days of the negative or equivocal PSMA scan.

A short questionnaire inquiring about the intended management will be sent to the referring physician at two timepoints: 1) the first is at the time of screening, prior to the Fluciclovine PET; and 2) the second is after the availability of the results of Fluciclovine PET.

Change in intended management will be recorded. Participants will be followed for 6 months and will be managed by their treating physician as per standard-of-care.

Inclusion Criteria:

• Age >= 18 years.
• Participant or legally authorized representative (LAR) must provide written informed consent before any study-specific procedures or interventions are performed.
• Patients with suspected BCR of prostate cancer after initial treatment, and a negative or equivocal PSMA PET, regardless of the findings on conventional imaging. Initial treatment may include prostatectomy and/or radiation therapy.
• PSA of 0.2 ng/mL or higher within 45 days of the scan.

Exclusion Criteria:

• Uncontrolled serious infection.
• Intercurrent illness or condition that would limit compliance with study requirements.
• Patients who have started any cancer treatment (systemic or radiation therapy) or who have started any supplements or herbal medications intended to treat cancer between the PSMA PET and Axumin PET/CT scans.