Maximizing diagnostic yield: A systematic review and deep dive into PSMA PET scan protocol variations for prostate cancer.

Prostate-specific membrane antigen (PSMA) PET has become a highly accurate imaging modality for prostate cancer (PCa), demonstrating superior diagnostic performance. However, substantial variability exists in imaging protocols beyond standard time-point acquisition, and the clinical value of these variations remains unclear. The aim of this study is to systematically review and compare PSMA PET protocols in PCa patients, focusing on detection rates and potential advantages, using extracted data from published studies. A systematic review was conducted in PubMed and Scopus through August 2025 for studies evaluating various PSMA PET protocols, including early, delayed, diuretic-aided, and hybrid/multiphasic imaging. Eligible studies included original research comparing these approaches with standard imaging. Ninety-seven studies (n = 8,428 patients) were included. Early imaging improved visualization of prostate bed and peri‑bladder lesions, increasing detection of local recurrence by 9-12% and enhancing tumor-to-background ratios up to fourfold, particularly in biochemical recurrence (BCR) with low PSA levels. Late imaging (2-4 h post-injection) consistently increased lesion contrast, detected additional lesions (up to 38.5%), and altered staging in up to 66.7% of cases, especially in equivocal or low-PSA settings. Diuretic-aided protocols reduced urinary artifacts, improved diagnostic confidence (63% to 91%), and revealed previously obscured lesions. Hybrid and multiphasic protocols demonstrated incremental gains in sensitivity and specificity, particularly in selected BCR populations, though benefits were context-dependent. Additional PSMA PET acquisitions provide complementary, scenario-specific diagnostic advantages but yield modest overall incremental benefit. Their judicious use, particularly in low-PSA BCR, equivocal findings, and pelvic disease, is recommended.