Combining Multiparametric Magnetic Resonance Imaging and Prostate-Specific Antigen Density in Selecting Patients for Prostate Biopsy

Introduction: Multiparametric magnetic resonance imaging (mpMRI) combined with prostate-specific antigen density (PSAd) has emerged as an effective risk-stratification tool for guiding prostate biopsy decisions. This study aimed to determine the optimal, clinically feasible biopsy strategy by combining the mpMRI Prostate Imaging-Reporting and Data System (PI-RADS) score and PSAd to minimize unnecessary biopsies while maximizing the detection of clinically significant prostate cancer (csPCa; Gleason score {GS} ≥7), using transperineal targeted and systematic biopsy as the reference standard. Methods: We retrospectively analyzed data from 511 men with clinical suspicion of prostate cancer (PCa) (PSA: >4 ng/mL; PI-RADS ≥3), who underwent pre-biopsy mpMRI and a subsequent combination of targeted and systematic transperineal prostate biopsy. Various mpMRI/PSAd thresholds were assessed based on their accuracy for detecting csPCa, their predictive value, the proportion of avoided biopsies, and net benefit and outcomes from decision curve analysis. Results: The overall analysis showed that the optimal strategy was to perform biopsy for lesions assessed as PI-RADS 4 and 5 or PI-RADS 3 lesions with PSAd of ≥0.15 ng/mL/mL. This combined approach yielded a negative predictive value (NPV) of 91% and a positive predictive value (PPV) of 43%. Implementing this strategy would have avoided biopsy in 16% (80/511) of the men and reduced the overdiagnosis of insignificant PCa by 9% (15/159) while missing only 4% (7/194) of csPCa cases. Conclusion: Combining mpMRI with PSAd provides a robust, risk-stratified approach to PCa diagnosis. Men with equivocal mpMRI findings (PI-RADS 3) and low PSAd (<0.15 ng/mL/mL) may safely defer immediate prostate biopsy, reducing unnecessary procedures and the burden of overdiagnosis.