PSMA PET/CT-Guided Biopsy Improves Detection of Significant Prostate Cancer After Nondiagnostic MRI

Prostate cancer can be difficult to detect when magnetic resonance imaging (MRI) findings are negative or inconclusive. Men with persistent clinical risk factors may still require biopsy, yet standard sampling can miss clinically significant disease and lead to additional procedures without resolving the diagnosis. To improve detection in these cases, researchers have evaluated whether targeted biopsy guided by an alternative imaging technique can identify cancers that MRI may overlook.

Researchers at the Nuclear Medicine Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna evaluated prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-targeted biopsy in men with negative or inconclusive MRI findings. The approach uses PET/CT to identify suspicious areas and direct prostate tissue sampling, complementing systematic biopsy, which samples predefined regions of the gland. Multiparametric MRI can miss an estimated 20%–30% of clinically significant prostate cancers in patients with negative or equivocal findings.

In the prospective, single-center FUPERMAN study, 63 men with negative or inconclusive MRI scans underwent gallium-68 PSMA-11 PET/CT followed by PET fusion-guided biopsy. Eleven participants also underwent dynamic total-body PET imaging. Researchers compared targeted and systematic biopsy performance and assessed whether imaging measurements could help predict clinically significant cancer. The study was published in The Journal of Nuclear Medicine in 2026.

PSMA PET/CT was positive in 25 of the 26 men ultimately diagnosed with clinically significant prostate cancer. Targeted biopsy detected clinically significant disease in 37% of participants, compared with 21% using systematic biopsy alone. Combining the two approaches increased the detection rate to 41%. Maximum standardized uptake value (SUVmax) was independently associated with clinically significant disease, while exploratory dynamic imaging showed distinct kinetic patterns in more aggressive lesions, particularly when imaging findings were unclear.

The findings suggest that PSMA PET/CT may help guide biopsy in men who remain at clinical risk despite negative or inconclusive MRI findings. By directing sampling toward the most suspicious areas, the approach could improve cancer detection and risk assessment, although larger studies are needed to confirm its clinical value.

“Our findings suggest that PSMA PET/CT could provide an additional tool for identifying men who remain at risk despite nondiagnostic MRI findings and for directing the biopsy toward the most suspicious area. If confirmed in larger studies, this approach could make the diagnostic pathway more accurate and personalized,” said Andrea Farolfi, M.D., a nuclear medicine physician at the Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna.

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