Seek and Find: Current Prospective Evidence for Prostate-specific Membrane Antigen Imaging to Detect Recurrent Prostate Cancer

Context: Men with biochemically relapsed prostate cancer face a clinical conundrum. Depending on the detected distribution of disease, treatment goals may range from cure with focal therapy to palliative with systemic therapy to expectant observation. Retrospective studies of prostate-specific membrane antigen (PSMA)-based imaging demonstrate higher disease detection rates than conventional imaging. Objective: This review focuses on available prospective evidence for diagnostic use of PSMA-based imaging to accurately restage recurrent prostate cancer and explores the potential clinical impact, near future uses, and challenges for PSMA-based imaging in this setting. Evidence acquisition: PubMed and EMBASE databases were searched for prospective studies with primary, secondary, or exploratory endpoints evaluating PSMA-based imaging for patients with recurrent prostate cancer published in English in the past 10 yrs. Evidence synthesis: We reviewed 48 prospective studies evaluating the role of PSMA positron emission tomography (PET) in recurrent prostate cancer. These studies establish the diagnostic accuracy and safety of PSMA PET using the Ga-68-PSMA-11 and (FDCFPyL)-F-18 radiotracers even at lower prostate-specific antigen (PSA) levels (0.5 <= PSA < 1.0 ng/m: disease detection rate 51-78%). The use of PSMA PET has been shown to result in changes in management in up to two-thirds of patients. Conclusions: There is now higher-level regulatory-quality prospective evidence for PSMA-based imaging for the detection of recurrent prostate cancer. There is prospective evidence of superiority over cross-sectional imaging and bone scintigraphy, as well as for the alterations in disease management as a result of PSMA-based imaging. Patient summary: When the prostate-specific antigen (PSA) level is rising after primary therapy, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is excellent at detecting and localizing prostate cancer, even at low PSA levels. Those who benefit best from treatment modifications based on PSMA PET findings are yet to be defined. (C) 2021 Published by Elsevier B.V. on behalf of European Association of Urology.