Objectives: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment.
Methods: In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308 biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were used to study their capability to increase the specificity of total serum PSA in predicting prostate biopsy results.
Results: Using age-specific PSA reference ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies would have been obtained with a loss of detected cancers of 12% (11). For the use of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively. Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less and an abnormal DRE as indicators for biopsy would reduce the number of biopsies by 37% (112) and the number of detected cancers by 11% (7). The biopsy to prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal loss of cancer detection of 3% (2) with a reduction in the number of biopsies of 17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS and DRE would have reduced the number of biopsies by 30% (102), and the number of cancers detected by 6% (4).
Conclusions: The most cost-effective protocol for screening prostate carcinoma appears to be prescreening by total serum PSA. The F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL, but the best threshold remains to be assessed.