Background: Prostate-Specific Antigen (PSA) is widely used for Prostate Cancer (PCa) screening, but its low specificity often leads to false-positive results and unnecessary biopsies. To address this issue, we introduced Age-Adjusted Prostate-Specific Antigen Density (A-PSAD) as a potential biomarker to improve screening accuracy for PCa and Clinically Significant Prostate Cancer (csPCa).
Methods: In this study, 663 patients who underwent prostate biopsy between 2020 and 2024 were included. The diagnostic performance of A-PSAD, PSAD, and other biomarkers was compared. Key variables, including age, diabetes history, FPSA, prostate volume, and A-PSAD, were selected using Lasso regression to develop a nomogram prediction model (Nomo1). Additionally, the PI-RADS score was incorporated into a second model (Nomo2).
Results: A-PSAD outperformed PSAD in PCa and csPCa screening. For PCa, A-PSAD had a higher AUC (0.753 vs. 0.732) with 71.86% sensitivity and 70.69% specificity, compared to PSAD's 74.87% and 63.15%. For csPCa, A-PSAD's AUC was 0.731 versus 0.708, with sensitivities of 76.27% and 57.61%. The nomogram model, based on Lasso-selected variables, achieved AUCs of 0.796 and 0.812 in the training and validation sets, with C-indices of 0.7870 and 0.7935, indicating good predictive performance. Decision curve analysis showed high clinical benefit across most risk thresholds. Incorporating PI-RADS, the Nomo2 model improved diagnostic performance in high-risk patients (AUC 0.8202) without significant difference from Nomo1 (AUC 0.8198, p > 0.05).
Conclusion: A-PSAD offers a better balance between sensitivity and specificity compared to PSAD, reducing false positives and unnecessary biopsies, and presents a promising tool for personalized PCa screening.
Keywords: clinically significant prostate cancer; diagnosis; lasso regression; prostate cancer; prostate‐specific antigen density.
© 2026 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.