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 (SUVmax) and dynamic total-body PET parameters in predicting csPCa.

Methods

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.

Results

PET-TB detected significantly more csPCa than did SB (37% vs. 21%; P = 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%. SUVmax independently predicted csPCa (odds ratio, 51.2; 95% CI, 5.6-2713.9; P = 0.015), with a threshold of 11.4 yielding 100% specificity. In dynamic PET analysis, csPCa showed irreversible kinetics, and Ki /k 3 parameters improved lesion discrimination beyond SUV, especially in equivocal (PRIMARY score 3) lesions.

Conclusion

PSMA PET/CT-guided targeted biopsy enhances csPCa detection in men with negative or equivocal mpMRI, with added predictive value from SUVmax and dynamic PET metrics. These promising findings should be validated in larger multicenter trials.