Utility of Prostate Health Index Density for Biopsy Strategy in Biopsy-Naïve Patients With PI-RADS v2.1 Category 3 Lesions

Background: Category 3 lesions in PI-RADSv2.1 pose diagnostic challenges, complicating biopsy decisions. Recent biomarkers like prostate health index (PHI) have shown higher specificity in detecting clinically significant prostate cancer (csPCa) than prostate-specific antigen (PSA). Yet their integration with MRI remains understudied. Purpose: To evaluate the utility of PSA and PHI with its derivatives for detecting csPCa in biopsy-naïve patients with category 3 lesion on initial prostate MRI scan. Study Type: Retrospective. Population: One hundred ninety-three biopsy-naïve patients who underwent MRI, PSA, and PHI testing, followed by both targeted and systematic biopsies. Field Strength/Sequence: Turbo spin-echo T2-weighted imaging, diffusion-weighted single-shot echo-planar imaging, and dynamic contrast-enhanced T1-weighted fast field echo sequence imaging in 3 T. Assessment: PHI density (PHID) and PSA density (PSAD) derived by dividing serum PHI and PSA with prostate volume (MRI based methodology suggested by PI-RADSv2.1). Risk-stratified models to evaluate the utility of markers in triaging patients for biopsy, including low-, intermediate-, and high-risk groups. Statistical Tests: Independent t-test, Mann–Whitney U test, Mantel–Haenszel test, generalized estimating equation, and receiver operating characteristic (ROC) curve analysis were used. Statistical significance defined as P < 0.05. Results: CsPCa was found in 16.6% (32/193) of patients. PHID had the highest area under the ROC curve (AUROC) of 0.793, followed by PHI of 0.752, PSAD of 0.750, and PSA of 0.654. PHID with two cut-off points (0.88/mL and 1.82/mL) showed the highest potential biopsy avoidance of 47.7% (92/193) with 5% missing csPCa, and the lowest intermediate-risk group (borderline decision group) at 38.9% (75/193), compared to PSA and PHI. Data Conclusion: PHID demonstrated better potential in triaging patients with category 3 lesions, possibly aiding more selective and confident biopsy decisions for csPCa detection, than traditional markers. Evidence Level: 4. Technical Efficacy: Stage 5.