Current and emerging clinical applications of PSMA-PET diagnostic imaging for prostate cancer

Abstract

Prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PCa) cells and several PSMA ligands for PET imaging (PSMA-PET) are now available worldwide. ⁶⁸Ga-PSMA-11 has already received American Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval, and PSMA-PET is currently suggested by several international guidelines to investigate PCa in different clinical settings. In primary PCa, PSMA-PET has been shown to be superior to cross-sectional imaging for the detection of pelvic lymph nodes and distant metastases with subsequent clinical management changes. Additionally, it might also have a role in intraprostatic tumor localization, especially when combined with multiparametric MRI. In a setting of PCa recurrency higher detection rates were observed when compared to all other available imaging techniques, especially at low PSA values. Furthermore, PSMA-PET consistently led to a shift in clinical management, thus increasing the proportion of radiotherapy, surgery, or other focal therapies at the expense of systemic options and/or no treatment. In oligometastatic disease after radical surgery, PSMA-PET may be relevant in guiding a metastases-directed therapy approach, as preliminary data seem to suggest a benefit in terms of progression-free survival after treatment of PSMA-PET positive lesions. As a staging and gatekeeping technique, it represents a reliable whole-body imaging procedure in combination with second-line therapy of castration-resistant PCa (CRPC) as well as pivotal when assessing patients eligible for radioligand therapy such as ¹⁷⁷Lu-PSMA. This critical review aims at providing a comprehensive overview of the latest literature on the current (or emerging) main indications as well as a general outlook of the recommended interpretation criteria while reading PSMA-PET imaging.