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