PSMA PET/CT–Targeted Biopsy in Men with Negative or Equivocal Multiparametric MRI and Exploratory Dynamic Total-Body PET: The FUPERMAN Study

Prostate-specific membrane antigen (PSMA) PET/CT may enhance detection of clinically significant prostate cancer (csPCa) in men with negative or equivocal multiparametric MRI (mpMRI), a setting where diagnostic uncertainty persists. This study assessed the diagnostic performance of PSMA PET/CT–guided targeted biopsy (PET-TB) versus systematic biopsy (SB) and explored the value of semiquantitative (SUV_max) and dynamic total-body PET parameters in predicting csPCa. <b>Methods:</b> This is a prospective, single-center study that enrolled 63 men with PI-RADS 2–3 mpMRI findings between March 2023 and July 2025. All underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT followed by transperineal prostate biopsy. A subset of 11 patients underwent dynamic total-body PET. The primary endpoint was detection of csPCa (International Society of Urological Pathology score of ≥2). We compared diagnostic yields of PET-TB and SB, evaluated predictors via logistic regression, and analyzed dynamic PET data using kinetic modeling. <b>Results:</b> PET-TB detected significantly more csPCa than did SB (37% vs. 21%; <i>P</i> = 0.021), achieving a sensitivity of 96%, a specificity of 49%, a positive predictive value of 57%, and a negative predictive value of 95%. Combining PET-TB with SB increased the csPCa detection rate to 41%. SUV_max independently predicted csPCa (odds ratio, 51.2; 95% CI, 5.6–2713.9; <i>P</i> = 0.015), with a threshold of 11.4 yielding 100% specificity. In dynamic PET analysis, csPCa showed irreversible kinetics, and <i>K_i</i>/<i>k</i>₃ parameters improved lesion discrimination beyond SUV, especially in equivocal (PRIMARY score 3) lesions. <b>Conclusion:</b> PSMA PET/CT–guided targeted biopsy enhances csPCa detection in men with negative or equivocal mpMRI, with added predictive value from SUV_max and dynamic PET metrics. These promising findings should be validated in larger multicenter trials.