A prospective study reports that PSMA PET/CT-guided targeted biopsy finds clinically significant prostate cancer in 37% of men with negative or inconclusive MRI results—nearly doubling detection when compared with MRI alone. The work also shows higher yield when PSMA PET/CT targeting is combined with systematic biopsy. The findings directly address a common pre-biopsy uncertainty: MRI can undercall lesions, particularly in patients with inconclusive imaging. By leveraging PSMA PET/CT lesion localization, targeted sampling appears to recover missed clinically meaningful disease. For clinical practice, the key impact is improved diagnostic accuracy in the MRI-negative subgroup, which can influence downstream decision-making for active surveillance versus treatment.