PSA density correlates to pathology T stage and ISUP grade: insights from a cohort of 3568 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 3568 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, stratified rank 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. Within the high-risk category, high biopsy ISUP and pathology ISUP grades were associated with lower PSAD levels (r = -0.59 and - 0.49 respectively). PSAD levels were associated with four adverse pathology outcomes, namely positive surgical margins, nodal involvement, ISUP ≥ 4 upgrading and pT ≥ 3 upstaging. 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 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.