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

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. 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). MRI-derived prostate volumes were significantly lower than TRUS-derived volumes (median 47.0 vs. 52.5 mL, < 0.001), resulting in higher MRI-PSAD values (median 0.14 vs. 0.12 ng/mL/mL, < 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, = 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%). 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.