IsoPSA density improves risk stratification and biopsy decision-making for clinically significant prostate cancer.

[OBJECTIVES] To evaluate the diagnostic performance of IsoPSA density for detecting clinically significant prostate cancer (csCaP), and its utility in guiding biopsy decision-making.

[MATERIALS AND METHODS] We conducted a retrospective review of 574 patients who underwent IsoPSA testing, prostate MRI, and image-guided biopsy within 1 year. IsoPSA density was calculated as IsoPSA value divided by MRI-derived prostate volume. Multivariable logistic regression, receiver operating characteristic (ROC) analysis, and decision curve analysis were used to assess predictive value. Subgroup analyses were performed in patients with large prostates (>70 ml) and negative MRI (PI-RADS 1-2).

[RESULTS] The overall prevalence of csCaP on biopsy was 33.8%. IsoPSA density was an independent predictor of csCaP and performed similarly to PSA density, while outperforming PSA and IsoPSA in ROC and decision curve analyses. In the full cohort, IsoPSA density achieved an AUC of 0.69 and demonstrated a high negative predictive value (NPV) of 79% at the optimal cutoff of 0.21. Among men with negative MRI (n = 238), an IsoPSA density threshold of 0.17 yielded an NPV of 97% and sensitivity of 85% for ruling out csCaP. In men with large prostates, higher IsoPSA density trended with increased csCaP risk, though not statistically significant.

[CONCLUSIONS] IsoPSA density performed comparably to PSA density and outperformed traditional clinical predictors of csCaP. In MRI-negative men, its high negative predictive value supports its use as a non-invasive tool to reduce unnecessary biopsies. IsoPSA density may serve as a valuable adjunct in contemporary prostate cancer diagnostic pathways and warrants further validation.