A Systematic Review of the Variability in Performing and Reporting Intraprostatic Prostate-specific Membrane Antigen Positron Emission Tomography in Primary Staging Studies

Context: Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths in men worldwide. Men at risk are typically offered multiparametric mag-netic resonance imaging and, if suspicious, a targeted biopsy. However, false -negative rates of magnetic resonance imaging are consistently 18%; therefore, there is growing interest in improving the diagnostic performance of imaging through novel technologies. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is being utilised for PCa staging and, more recently, for intrapro-static tumour localisation. However, significant variability has been observed in how PSMA PET is performed and reported.Objective: In this review, we aim to evaluate how pervasive this variability is in tri-als investigating the performance of PSMA PET in primary PCa workup. Evidence acquisition: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed an optimal search in five dif-ferent databases. After removing duplicates, 65 studies were included in our review. Evidence synthesis: Studies dated back as early as 2016, with numerous different source countries. There was variation in the reference standard for PSMA PET, with some using biopsy specimens or surgical specimens, and in some cases, a combina-tion of the two. Similar inconsistencies were noted when studies selected histolog-ical definitions of clinically significant PCa, while some omitted their definition altogether. The most significant variations in performing PSMA PET were the radio -tracer type, dose, acquisition time after injection, and the PET camera being uti-lised. Substantial variation in the reporting of PSMA PET was noted, with no consistency in defining what constitutes a positive intraprostatic lesion. Across 65 studies, four different definitions were used.Conclusions: This systematic review has highlighted considerable variation in obtaining and performing a PSMA PET study in the context of primary PCa diagno-sis. Given the discrepancy in how PSMA PET was performed and reported, it ques-tions the homogony of studies from centre to centre. Standardisation of PSMA PET is required for this to become a consistently useful and reproducible modality in the diagnosis of PCa.Patient summary: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is being utilised for staging and localisation of prostate cancer (PCa); however, there is significant variability in performing and reporting PSMA PET. Standardisation of PSMA PET is required for results to be consistently useful and reproducible for the diagnosis of PCa.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).