Evaluating Prostate-Specific Antigen (PSA) Density Thresholds for Detecting Clinically Significant Prostate Cancer in Prostate Imaging Reporting and Data System (PI-RADS) 3 Lesions: A Retrospective Cohort Study.

Introduction  Prostate cancer is one of the most common cancers in the world. Equivocal prostate magnetic resonance imaging (MRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] 3) remain a diagnostic challenge. The use of prostate-specific antigen density (PSAD) has been suggested to help risk-stratify this cohort of patients to help guide the decision to biopsy. This study aimed to evaluate the diagnostic performance of PSAD across multiple cut-offs in detecting clinically significant prostate cancer (csPCa) in patients with PI-RADS 3 lesions.  Methods  A retrospective audit of 194 men with PI-RADS 3 lesions on multiparametric magnetic resonance imaging (mpMRI) who underwent prostate biopsy was performed. Age, prostate-specific antigen (PSA), prostate volume, and PSAD were collected. Receiver operating characteristic (ROC) analysis was used to assess model accuracy. Univariate and multivariate logistic regression were performed to identify significant predictors of csPCa. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at PSAD thresholds of 0.10, 0.15, and 0.20 ng/mL2. Results  csPCa was identified in 47 (24.2%) of patients. Median prostate volume was significantly lower, and PSAD was considerably higher, in this cohort of patients (p < 0.001). ROC analysis showed an area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.65-0.79). Multivariate analysis confirmed that PSAD remained a significant predictor for csPCa (odds ratio (OR) 1.6, 95% CI 1.2-2.0, p < 0.001). Sensitivity and specificity at PSAD ≥ 0.10 ng/mL2, ≥ 0.15 ng/mL2, and ≥0.20 ng/mL2 were 0.92/0.29, 0.68/0.65, and 0.53/0.84, respectively. PPV increased (0.29, 0.39, and 0.52) while NPV remained high (0.91,0.87,0.85) across these cut-offs. Conclusion  PSAD is demonstrated as a good predictor for csPCa in PI-RADS 3 lesions. A threshold of 0.15 ng/mL2 provides a good balance between sensitivity and specificity and supports its use in determining biopsy decisions in this cohort. Validation in larger multicentre cohorts is warranted.