The investigators are attempting to determine if a new form of imaging called 18F-DCFPyL PET/CT is helpful to physicians in deciding how to manage suspected prostate cancer recurrence. This imaging uses a Positron Emission Tomography/Computed Tomography (PET/CT) scan using a radioactive tracer 18F-DCFPyL that is concentrated in prostate cancer cells and can potentially identify cancer cells throughout the body. The combination of 18F-DCFPyL PET/CT can potentially identify areas of prostate cancer recurrence not seen with usual imaging [bone scan, computed tomography (CT) thorax, abdomen and pelvis, plus multi-parametric magnetic resonance imaging (MRI)].

The study will evaluate the utility of investigational restaging with 18F-DCFPyL PET/CT following conventional imaging (bone scan, CT thorax, abdomen and pelvis plus multi-parametric pelvic MRI) in detecting the prevalence of metastatic disease among men with biochemical recurrence after radical radiotherapy treatment to the prostate. Men treated with primary radiation with external beam or brachytherapy will be eligible. Eighty (80) eligible consenting patients with biochemical recurrence and potentially suitable for local salvage or targeted ablative therapies will be registered and imaged with conventional imaging (bone scan, CT thorax, abdomen and pelvis plus multi-parametric pelvic MRI) followed by investigational restaging with 18F-DCFPyL PET/CT. Characterizing sites of disease identified by the combination of 18F-DCFPyL PET/CT with conventional imaging versus 18F-DCFPyL PET/CT alone will be used to explore the potential of 18F-DCFPyL PET/CT as a single restaging study in men with biochemical recurrence. While further investigation and treatment after restaging will be at the discretion of the investigator and the patient, the actual treatment/management, treatment outcomes and quality of life will be recorded in an electronic database at 6, 12, 24 and 36 months after re-staging. Such longitudinal analyses of management and outcomes will be useful in characterizing the disease trajectory, response to treatment and quality of life for patients whose recurrent disease is managed based on comprehensive restaging using the combination of conventional imaging and 18F-DCFPyL PET/CT.

Inclusion Criteria:

• Previous external beam radiotherapy or brachytherapy for localized disease (T1-T2, Gleason < 7 and PSA < 20) or (T1-2, Gleason 8, prostatic specific antigen (PSA)<10)
• Interval to biochemical failure more than 12 months from last radical therapeutic intervention
• Biochemical failure confirmed on at least 3 consecutive PSA measurements each taken at least 1 month apart
• PSA at time of enrollment more than nadir+2.0ng/ml (Phoenix definition of biochemical failure)
• Karnofsky performance status 70 or better [Eastern Cooperative Oncology Group (ECOG) 0,1]
• Total serum testosterone level >1nmol/l (if prior treatment with hormone therapy)

Exclusion Criteria:

• CT or bone scan within 6 months of enrollment
• Patients whose prior radiotherapy was delivered with palliative intent
• Patients with known metastatic disease
• Extensive co-morbidities precluding potential ablative salvage procedures
• Prior history of invasive non-cutaneous malignant disease unless disease free for at least 5 years
• Already on systemic anticancer treatment (androgen deprivation or chemotherapy)
• Inability to comply with the imaging requirements e.g. inability to lie supine for one hour
• Allergy or contraindication to MRI or CT contrast agents or PET tracer to be used as part of the imaging
• Insufficient renal function [estimated glomerular filtration rate (eGFR) < 30 mL/min]