Use of the Percentage of Free Prostate-Specific Antigen to Enhance Differentiation of Prostate Cancer From Benign Prostatic Disease: A Prospective Multicenter Clinical Trial

JAMA. 1998 May 20;279(19):1542-7. doi: 10.1001/jama.279.19.1542.

Abstract

Context: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use.

Objective: To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied.

Design: Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif).

Setting: Seven nationwide university medical centers.

Participants: A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis.

Main outcome measures: A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients.

Results: The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL.

Conclusions: Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Specimen Collection
  • Diagnosis, Differential
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Probability
  • Prospective Studies
  • Prostate-Specific Antigen / blood*
  • Prostatic Hyperplasia / blood*
  • Prostatic Hyperplasia / diagnosis
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / pathology
  • Reference Standards
  • Risk
  • Sensitivity and Specificity
  • Statistics, Nonparametric

Substances

  • Prostate-Specific Antigen