PSA Density strongly correlates to Pathology T stage and ISUP grade: Insights from a Cohort of 3,568 Radical Prostatectomy Cases

Introduction : Prostate-specific antigen density (PSAD) is a valuable detection tool for prostate cancer (PCa) with PSA levels in the "gray zone" (4–10 ng/mL). However, its relationship with final pathology outcomes remains limited, especially on large cohorts. Objective : This study aimed to describe PSAD distributions according to final pathology findings (pathological T stage and ISUP grade) and identify clinical and pathological factors influencing PSAD variations. Methods : We analyzed a prospective cohort of 3,568 patients who underwent radical prostatectomy for PCa in our center between 2007 and 2025. PSAD was calculated using serum PSA (ng/mL) divided by prostate weight (g) from pathology reports. Associations between PSAD and pathology T stage, ISUP grade, total testosterone, cholesterol levels, and statin use were done using Spearman’s correlation coefficient, an ANCOVA analysis and a multiple linear regression. Results : The median PSAD was 0.17 ng/mL/g (IQR: 0.12–0.25). PSAD levels increased gradually with advanced pathology T stage (pT3a and T3b) and higher ISUP grade (p < 0.001 for both). After adjusting for confounding covariates (age and D’Amico risk classification), PSAD remained significantly associated with Pathology T stage and ISUP. In high-risk patients, PSAD was negatively correlated with biopsy ISUP (r=-0.59), pathology ISUP grade (r=-0.49), and total testosterone (r=-0.31). Multivariate analysis identified higher biopsy ISUP grade and PSA levels as positive predictors of PSAD, while age, BMI, and testosterone were negatively associated. Conclusion : PSAD strongly correlates with PCa aggressiveness on pathology, making it a clinically relevant biomarker. Future studies should investigate PSAD’s relation with adverse oncological outcomes, including biochemical recurrence.