Prostate-specific Antigen Density and Clinically Significant Prostate Cancer: Impact of Prostatic Volume in PI-RADS 3 Lesions; High Volume Single-center Analysis

Objective: Prostate-specific antigen density (PSAd) has gained traction as a superior diagnostic marker, compared with PSA alone, for predicting clinically significant prostate cancer (csPCa).However, prostate gland volume may affect the diagnostic accuracy of PSAd.To evaluate how prostate volume influences the diagnostic performance of PSAd for detecting csPCa in patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions.Materials and Methods: We retrospectively analyzed 576 patients with PI-RADS 3 lesions who underwent PSA testing, multiparametric magnetic resonance imaging (MRI), and cognitive-and fusion-guided transrectal prostate biopsies between 2017 and 2025.PSAd was calculated as serum PSA divided by MRI-measured prostate volume.Patients were stratified into three groups according to prostate volume: 30 mL, 31-50 mL, and 51 mL.csPCa was defined as International Society of Urological Pathology grade 2.Diagnostic performance of PSAd was assessed using receiver operating characteristic (ROC) curve analysis with volume-specific cut-offs. Results:The overall csPCa detection rate was significantly higher in patients with prostates 30 mL (p<0.001).Across all volume groups, csPCa detection remained <5% when PSAd <0.10 ng/mL/mL.For glands 30 mL, csPCa rates rose sharply above this threshold.ROC analysis revealed that small prostates had a slightly higher diagnostic accuracy area under the curve (AUC) 0.668 compared with intermediate (AUC 0.599) and large (AUC 0.633) glands.Optimal PSAd cut-offs were narrowly distributed (0.1058-0.1531), but diagnostic sensitivity varied with volume. Conclusion:The findings indicate that the diagnostic performance of PSAd in predicting csPCa is influenced by prostate volume.Instead of proposing definitive universal cut-off values, our results suggest that lower PSAd thresholds may be considered in patients with larger prostate volumes, particularly in borderline cases such as PI-RADS 3 lesions.Incorporating prostate volume into PSAd interpretation may improve risk stratification and contribute to more individualized biopsy decision-making.