Imaging Prostate Cancer: Clinical Utility of Prostate-Specific Membrane Antigen
David Kuppermann, Jeremie Calais, Leonard S. Marks
Abstract
PURPOSE: Our goal was to review the pathway and pertinent materials leading to approval of prostate-specific membrane antigen (PSMA) scanning by the U.S. Food and Drug Administration (FDA). MATERIALS AND METHODS: Beginning with the pivotal trials and working backward, we summarize the evolution of PSMA scanning, beginning with the discovery of the molecule, the mechanism of action to identify prostate cancer, the route to the present-day test and some of the major publications leading to each step of the sequence. From the thousands of PSMA articles listed on PubMed®, the present review is focused on the 4 large U.S. trials incorporating university studies of the gallium-68 compound and commercial studies of the fluorine-18 compound. The review further focuses on the role of PSMA scanning for both initial staging of prostate cancer and diagnosis of recurrent prostate cancer. RESULTS: F-DCFPyL) was approved on the basis of multisite registration trials (CONDOR and OSPREY). Sensitivity and specificity of PSMA scanning exceeds that of any other imaging method currently available for initial staging of prostate cancer and diagnosis of recurrent disease. The accuracy of PSMA scanning is attributed to the great image contrast (high signal-to-noise ratio), a property deriving from the high PSMA tracer uptake by prostate cancer cells. That property can be estimated quantitatively by a metric, the standardized uptake value. A follow-on PSMA compound, the theranostic lutetium-177, is currently pending FDA approval for treatment of metastases. CONCLUSIONS: PSMA scanning is a disruptive technology that promises to transform the way prostate cancer is initially staged, recurrence is diagnosed and some advanced cases are treated.