Diagnostic Properties of Total and Free Prostate-Specific Antigen to Predict Overall and Clinically Significant Prostate Cancer Among Men With Low Testosterone and Prior Negative Biopsy

Urology. 2020 Mar:137:97-101. doi: 10.1016/j.urology.2019.11.004. Epub 2019 Nov 14.


Objective: To evaluate whether total serum PSA, free-PSA ratio and PSA density have similar diagnostic properties for detecting prostate cancer (PCa) and clinically-significant (cs) PCa in men with normal testosterone compared to men with low testosterone with a prior negative biopsy.

Methods: We conducted a retrospective analysis of 3295 men undergoing a 2-year prostate biopsy following a negative prestudy biopsy in the placebo arm of the Reduction by Dutasteride of PCa Events (REDUCE) study. Men were divided in 2 groups based on testosterone level < or ≥300 ng/dL. Diagnostic properties of total serum PSA, free-PSA ratio, and PSA density to predict PCa and csPCa, defined as Gleason score ≥7, were determined for several thresholds and plotted as receiver operator characteristic curves.

Results: A total of 603 men (18.3%) had low testosterone. The prevalence of PCa and csPCa was 92 (15.3%) and 27 (4.5%), respectively, for low testosterone men compared to 458 (17.0%) and 138 (5.1%), correspondingly, for normal testosterone men. Total PSA, free-PSA ratio and PSA density showed similar sensitivity, specificity, and accuracy to predict PCa and csPCa among low testosterone men compared to normal testosterone men.

Conclusion: Among subjects in a clinical trial with a prior negative biopsy, total PSA, free-PSA ratio and PSA density have comparable diagnostic characteristics for PCa screening in low and normal testosterone men.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 5-alpha Reductase Inhibitors / therapeutic use
  • Aged
  • Biopsy / methods
  • Double-Blind Method
  • Dutasteride / therapeutic use*
  • Early Detection of Cancer / methods
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Outcome Assessment, Health Care
  • Prostate / pathology*
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms* / blood
  • Prostatic Neoplasms* / diagnosis
  • Prostatic Neoplasms* / pathology
  • Sensitivity and Specificity
  • Testosterone / blood*


  • 5-alpha Reductase Inhibitors
  • Testosterone
  • Prostate-Specific Antigen
  • Dutasteride