Background: Prostate-specific antigen (PSA) testing is widely used in the evaluation of prostate disorders, but its diagnostic accuracy is limited by the influence of prostate size, as benign prostatic enlargement may produce PSA elevations similar to malignancy.

Aim: This study assessed the quantitative relationship between prostate size and serum PSA levels and evaluated the diagnostic value of PSA density (PSAD) in improving prostate disease differentiation.

Materials and methods: A prospective cross-sectional study was conducted among 185 male patients aged 40 years and above who presented with prostate-related conditions at Crescent Diagnostic Laboratory, Onitsha, Anambra State. Prostate dimensions and volume were measured using transrectal ultrasound, while serum total and free PSA levels were determined using chemiluminescent immunoassay. PSA density was calculated as the ratio of total PSA to prostate volume. Data were analyzed using SPSS version 24, employing descriptive statistics, Pearson correlation, multiple linear regression, and receiver operating characteristic (ROC) curve analysis.

Results: The mean age of the participants was 61.1 ± 10.7 years, and the mean prostate volume was 54.5 ± 53.5 cm³. Total PSA showed a moderate positive correlation with prostate volume (r = 0.403, p < 0.001) and a weaker correlation with age (r = 0.222, p = 0.002). Regression analysis demonstrated that prostate volume was a significant independent predictor of PSA levels, whereas age was not significant after adjustment. PSA and PSAD values were highest in patients with prostate cancer. ROC analysis revealed that PSAD had superior diagnostic performance (AUC = 0.941) compared with total PSA (AUC = 0.899). An optimal PSAD cut-off value of ≥ 0.214 ng/mL/cm³ achieved 100% sensitivity and 88.4% specificity, outperforming conventional PSA thresholds.

Conclusion: The prostate volume is a major determinant of serum PSA levels and that PSA density provides improved diagnostic accuracy. Incorporation of PSAD into routine prostate evaluation is recommended to reduce unnecessary biopsies and enhance evidence-based clinical decision-making.