Prostate-specific membrane antigen (PSMA) is a promising molecular target for prostate cancer (PCa) that has allowed the development of a novel diagnostic approach to PCA in the primary and recurrent settings.

To summarize available data and recommendations regarding the use of PSMA in newly diagnosed and recurrent PCa via a narrative review.

A literature review was conducted using MEDLINE (via PubMed) and Scopus. The search strategy included meta-analyses, reviews, and original studies on staging and restaging with ⁶⁸Ga-PSMA positron emission tomography (PET)/computed tomography (CT).

Studies comparing PSMA-targeted imaging and conventional imaging suggest superior performance of PSMA-targeted imaging in primary and recurrent PCa, albeit with several clinically relevant limitations. Pretreatment ⁶⁸Ga-PSMA PET/CT allowed more accurate PCa staging in compared to routine practice for high-risk cases, and identified a number of otherwise unknown metastatic lesions. In biochemically recurrent PCa, PSMA PET can reveal sites of recurrence with greater sensitivity and specificity than conventional imaging, potentially detecting a major proportion of occult disease. This review will help providers in applying the most up-to-date and relevant literature to (1) determine which patients truly have oligometastatic disease and (2) ascertain who is most likely to experience a meaningful response to local consolidation in the biochemical recurrence setting.

Data on PSMA diagnostic studies in primary and recurrent PCa highlight the accuracy and clinical application of PSMA PET. While this review and the evidence to date might lead to a perception of superiority in metastasis directed therapy, fundamental lack of phase III clinical trials with clinically meaningful outcomes are yet to be determined.

PSMA (prostate-specific membrane antigen) scans have shown great promise for initial evaluation of prostate cancer (PCa) and in detection of PCa recurrence. The benefits are more apparent for initial staging of PCa. There are more limited clinical trial results for PCa recurrence on how best to use this new technique to guide cancer treatment.