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 a lpha(1)-antichymotrypsin. Total PSA approximates the sum of the free a nd complexed forms. Preliminary investigations have illustrated the po tential benefits of using percent free PSA to enhance the clinical uti lity of PSA in distinguishing benign prostate disease from prostate ca ncer. The current study defines the optimal range of total PSA for mea suring percent free PSA (reflex range) and generates appropriate cutpo ints for percent free PSA within this range. Methods. A total of 413 p atients, 225 (54%) with benign prostate disease (mean age, 67 years) a nd 188 (46%) with prostate cancer (mean age, 66 years), who had PSA va lues between 2.0 and 20.0 ng/mL participated in the investigation. All patients underwent a sextant biopsy to establish the diagnosis. The s erum specimens were assayed with the AxSYM PSA assay (total PSA) and A xSYM Free PSA assay (Abbott Laboratories; Abbott Park, IL). Percent fr ee PSA was calculated for all patients. Receiver operating characteris tic (ROC) curves were generated for various ranges of total PSA to det ermine the reflex range that maximized the increase in sensitivity and specificity of percent free PSA over total PSA. Within the optimal ra nge, the ROC curves were utilized to generate cutpoints for percent fr ee PSA to be used in clinical practice. Results. The appropriate refle x 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 wa s 3.0 to 4.0 ng/mL to achieve 90% sensitivity for the detection of pro state 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 betwe en 3.0 and 4.0 ng/mL. The appropriate cutpoint for percent free PSA wh en 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 sh ould 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 (im proving sensitivity). In patients with a total PSA concentration rangi ng from 4.1 to 10.0 ng/mL, negative biopsies were eliminated (improvin g specificity). Copyright 1997 by Elsevier Science Inc.