Determination of the "reflex range" and appropriate cutpoints for percent free prostate-specific antigen in 413 men referred for prostatic evaluation using the AxSYM system.

Objectives: Prostate-specific antigen (PSA) exists in the serum in two clinically important molecular forms: free PSA and PSA complexed to alpha 1-antichymotrypsin. Total PSA approximates the sum of the free and complexed forms. Preliminary investigations have illustrated the potential benefits of using percent free PSA to enhance the clinical utility of PSA in distinguishing benign prostate disease from prostate cancer. The current study defines the optimal range of total PSA for measuring percent free PSA (reflex range) and generates appropriate cutpoints for percent free PSA within this range.

Methods: A total of 413 patients, 225 (54%) with benign prostate disease (mean age, 67 years) and 188 (46%) with prostate cancer (mean age, 66 years), who had PSA values between 2.0 and 20.0 ng/mL participated in the investigation. All patients underwent a sextant biopsy to establish the diagnosis. The serum specimens were assayed with the AxSYM PSA assay (total PSA) and AxSYM Free PSA assay (Abbott Laboratories; Abbott Park, IL). Percent free PSA was calculated for all patients. Receiver operating characteristic (ROC) curves were generated for various ranges of total PSA to determine the reflex range that maximized the increase in sensitivity and specificity of percent free PSA over total PSA. Within the optimal range, the ROC curves were utilized to generate cutpoints for percent free PSA to be used in clinical practice.

Results: The appropriate reflex range for the utility of percent free PSA was 3.0 to 10.0 ng/mL. The appropriate cutpoint for percent free PSA when the total PSA value was 3.0 to 4.0 ng/mL to achieve 90% sensitivity for the detection of prostate cancer was 0.19. This approach resulted in a biopsy rate of 73% and a cancer detection rate of 44% in men with a total PSA value between 3.0 and 4.0 ng/mL. The appropriate cutpoint for percent free PSA when the total PSA value was 4.1 to 10.0 ng/mL to ensure 95% sensitivity for detection of prostate cancer was 0.24. Within the range of 4.1 to 10.0 ng/mL, this approach resulted in 13% fewer negative biopsies and failure to detect 5% of the cancers.

Conclusions: Percent free PSA should be utilized in patients with a total serum PSA value between 3.0 and 10.0 ng/mL. In patients with a total PSA value between 3.0 and 4.0 ng/mL, percent free PSA enhanced the detection of prostate cancer (improving sensitivity). In patients with a total PSA concentration ranging from 4.1 to 10.0 ng/mL, negative biopsies were eliminated (improving specificity).