Prostate cancer (PCa) is the second most common malignancy worldwide, accounting alone for over 29% of cancers diagnosis in 2023 and leading to approximately over 350,000 deaths. Consequently, there exists a worldwide challenge to understand what the possible prevention strategies and the best treatments could be.1 For this reason, the Council of the European Union has recently proposed to strengthen cancer prevention through early detection, by improving cancer screening and ensuring access to screening programmes.2 At the moment, PCa screening is mainly based on digital rectal examination (DRE), prostate specific antigen (PSA) level and subsequent histological evaluation by transrectal ultrasound (TRUS)-guided biopsy for diagnosis.3 In particular, according to Gleason score (GS), PCa can be classified into clinically non-significant PCa (non-csPCa, GS = 6) and clinically significant PCa (csPCa, GS = 7-10), leading to diverse management and subsequent prognosis. With regards to the diagnostic workup of PCa, the European Association of Urology (EAU) guidelines recommend multiparametric magnetic resonance imaging (mpMRI) as standard of care imaging in biopsy-naïve patients, suggesting systematic biopsies to lesions with a prostate imaging reporting and data system (PI-RADS) score greater than 3.4 Numerous important studies have demonstrated that mpMRI correlates with histopathological PCa characteristics and have proved its superiority in terms of diagnostic accuracy with respect to transrectal biopsy.5 Despite that, other evidences suggest that mpMRI still misses csPCa in more than 13% of the cases, with high rate of false positive lesions with PI-RADS >4 and discordant results of positive predictive value (PPV) and specificity among studies.6,7 In addition, recent trends demonstrate that mpMRI-based fusion biopsy could miss some lesions located in the central and transition zones of prostate gland and thus, approximately 20% of patients could undergo unnecessary biopsies due to a false-positive PSA test.8 Another important aspect to take into consideration is the inter-reader variability of MRI due to operator's experience, which can lead to significant diagnostic misinterpretation especially in doubtful cases, such as PI-RADS 3 lesions.9,10 These limitations highlight the need for a “next-generation imaging” as a new tool for diagnostic evaluation of PCa. In this context, PET/CT with Prostate Specific Membrane Antigen (PSMA; PSMA-PET) has rapidly emerged as a useful resource complementing mpMRI role in the diagnostic management of PCa.11

The aim of our current contribution is to provide an overview and an update over the current literature on imaging detection of csPCa, with a particular focus on mpMRI, PET-CT and their comparison.