Background: Measurement of the free fraction of total prostate-specific antigen (fPSA%) has been proposed as a useful addition to total PSA for the detection of prostate cancer.
Methods: We assessed the performance of fPSA% in differentiating men with prostate cancer from men without cancer in a group of 1,709 subjects studied in five institutions.
Results: On the basis of PSA testing, digital rectal examination, and ultrasound examination conducted at one or more visits, 229 cancers were diagnosed. The mean fPSA% in men with cancer was 9.1% compared to 18.9% in men without cancer. The fPSA% varied by age, with men under 60 having a mean fPSA of 13.9% compared to 17.5% in men 60-69 years old and 19.8% in men over age 70. Significant associations of fPSA% with gland volume and PSA level were also observed. The sensitivity, specificity, and positive predictive value of different fPSA% cutoff levels were assessed in 513 men who underwent sextant biopsy. Sensitivity of 85.4%, 32.1% specificity, and a 39.2% positive predictive value were observed using an fPSA cutoff of 15% in men with PSA in the 4.0-9.9 ng/ml range. Sensitivity of 96.9%, 12.3% specificity, and a 36.2% positive predictive value were observed using an fPSA cutoff of 20% in the same men. If 15% fPSA had been used as a biopsy criterion in men with PSA of 4.0-9.9 ng/ml, the number of biopsies performed could have been reduced by 21.2%, with a concomitant reduction in cancer detection of 14.6%. Using a 20% fPSA criterion, biopsies would have been reduced 12.7%, with a 3.1% reduction in cancer detection.
Conclusions: These results provide some evidence that the detection of prostate cancer is enhanced by measuring fPSA% in addition to the established measure of total PSA level. Further research is needed to identify other markers that have better sensitivity and specificity.