Diagnostic and Clinical Impact of Imaging Modality on PSA Density: TRUS Versus MRI in Gray-Zone Prostate Cancer

Background: In this study, it was aimed to compare transrectal ultrasound (TRUS)- and magnetic resonance imaging (MRI)-derived prostate-specific antigen density (PSAD) in patients with gray-zone PSA levels (4-10 ng/mL), evaluate their diagnostic performance for clinically significant prostate cancer (csPCa), and assess the clinical implications of reclassification across commonly used thresholds. Methods: We retrospectively analyzed 202 men who underwent both TRUS and multiparametric MRI between January 2020 and June 2025. Prostate volume was measured using the ellipsoid formula for TRUS and contour-based planimetry for MRI. PSA density (PSAD) was calculated as total PSA (tPSA, ng/mL) divided by prostate volume (mL) for each modality: TRUS-PSAD and MRI-PSAD. Agreement between modalities was evaluated using Bland-Altman plots and correlation analyses. Reclassification at PSAD thresholds of 0.15, 0.20, and 0.30 ng/mL/mL was assessed using Cohen's κ and net reclassification improvement (NRI). Diagnostic performance for csPCa (ISUP grade group ≥ 2) was evaluated with ROC analysis and the DeLong test. Inter- and intra-observer reproducibility was determined using intraclass correlation coefficients (ICC) and Cohen's κ. Clinical utility was assessed by decision curve analysis (DCA). Results: MRI-derived prostate volumes were significantly lower than TRUS-derived volumes (median 47.0 vs. 52.5 mL, p < 0.001), resulting in higher MRI-PSAD values (median 0.14 vs. 0.12 ng/mL/mL, p < 0.001). Bland-Altman analysis demonstrated a negative bias for prostate volume (-3.2 mL) and a positive bias for PSAD (+0.03). Strong correlations were observed between TRUS and MRI measurements (r = 0.96 for volume and r = 0.94 for PSAD). MRI-PSAD frequently reclassified patients into higher risk categories, yielding positive net reclassification improvement for cancer cases across all thresholds, while introducing some negative reclassification among non-cancer cases. ROC analysis showed comparable overall diagnostic performance between TRUS-PSAD and MRI-PSAD (AUC 0.681 vs. 0.679, p = 0.91). However, MRI-PSAD demonstrated higher sensitivity at predefined thresholds at the expense of reduced specificity, reflecting a threshold-dependent shift rather than improved discrimination. Reproducibility was higher for MRI-derived measurements (ICC = 0.94; κ = 0.83) compared with TRUS (ICC = 0.86; κ = 0.71). Decision curve analysis indicated that MRI-PSAD, particularly when combined with PI-RADS ≥ 3, provided the greatest net clinical benefit at lower threshold probabilities (5-15%). Conclusions: MRI-derived PSA density produces systematically higher values than TRUS-based measurements due to inherent differences in prostate volume estimation. While this results in increased sensitivity at standard thresholds, overall discrimination remains unchanged. These findings support the use of modality-specific PSAD thresholds rather than uniform cutoffs across imaging techniques. In clinical practice, MRI-PSAD may provide additional value when interpreted in conjunction with PI-RADS, primarily through improved threshold calibration rather than enhanced diagnostic accuracy.