Prostate Specific Antigen Density and Clinically-Significant Prostate Cancer: The Influence of Prostatic Volume.

Background: Prostate specific antigen density (PSAd) is one of the strongest predictors of clinically-significant prostate cancer (csPCa) in risk calculators. There is little evidence on the effect of prostate volume on the diagnostic performance of PSAd. Our aim was to define the diagnostic accuracy of PSAd for predicting csPCa across prostate volumes.

Methods: 548 patients who underwent magnetic resonance imaging (MRI) and biopsy were included in this retrospective study. Patients were grouped by prostate volume; small (≤ 30 mL), medium (> 30 to < 50 mL), large (≥ 50 mL). Sensitivity and specificity of PSAd were assessed at thresholds of ≥ 0.10, ≥ 0.15, and ≥ 0.20 ng/mL/mL for two definitions of csPCa.

Results: At all PSAd thresholds and for both definitions of csPCa, there was a statistically significant and clinically-relevant difference in diagnostic performance across prostate volume groups. Sensitivity was highest in small glands, lowest in large glands; the opposite being true for specificity. Using a PSAd threshold of ≥ 0.15 ng/mL/mL, sensitivity for ISUP grade ≥ 2 PCa was 83.1%, 63.6%, and 33.3% for small, medium and large prostates (p ≤ 0.001) with specificities of 48.5%, 67.5% and 79.3%, respectively (p = 0.005).

Conclusions: Diagnostic performance of PSAd varied significantly by prostate volume, and by applying a single PSAd threshold across all prostate volumes risks missing csPCa in men with larger glands, whilst performing unnecessary biopsies in those with smaller glands. Defining PSAd thresholds according to prostate volume categories can therefore improve its use as a risk predictor for csPCa.