Over the last years, prostate magnetic resonance imaging (MRI) has gained a key role in the primary diagnosis of clinically significant prostate cancer (csPCa). While a negative MRI can avoid unnecessary prostate biopsies and the overdiagnosis of indolent cancers, a positive examination triggers biopsy samples targeted to suspicious imaging findings, thus increasing the diagnosis of csPCa with a sensitivity and negative predictive value of around 90%. The limitations of MRI, including suboptimal positive predictive values, are fueling debate on how to stratify biopsy decisions and management based on patient risk and how to correctly estimate it with clinical and/or imaging findings. In this setting, "next-generation imaging" imaging based on radiolabeled Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is expanding its indications both in the setting of primary staging (intermediate-to-high risk patients) and primary diagnosis (e.g., increasing the sensitivity of MRI or acting as a problem-solving tool for indeterminate MRI cases). This review summarizes the current main evidence on the role of prostate MRI and PSMA-PET as tools for the primary diagnosis of csPCa, and the different possible interaction pathways in this setting.
