Complexed prostate-specific antigen for early detection of prostate cancer in men with serum prostate-specific antigen levels of 2 to 4 nanograms per milliliter

Complexed PSA (cPSA) has been shown to improve specificity in the detection of prostate cancer over that of total PSA (tPSA) testing in men with tPSA values greater than the cutoff value of 4.0 ng/mL. However, recent studies have reported a 25% incidence of prostate cancer in men with tPSA values in the 2.5- to 4.0-ng/mL range. We performed a multicenter study of cPSA in a population of men who underwent prostate biopsies because of elevated PSA levels or abnormal digital rectal examination (DRE). As part of this study, we sought to assess the clinical value of cPSA in comparison to tPSA, the free/tPSA ratio (f/tPSA) and the complexed/tPSA ratio (c/tPSA) in early detection of prostate cancer in men with tPSA values in the range of 2 to 4 ng/mL. The study was performed at 7 centers. Sera were drawn from men who underwent biopsy procedures consisting of >10 prostate tissue cores. Receiver operating characteristic (ROC) analysis was performed from the results of patients with tPSA values in the range of 2 to 4 ng/mL, including men with suspicious as well as unremarkable findings on DRE. Sera were collected and tested with the Bayer tPSA and cPSA assay and the Beckman free PSA and tPSA assays. ROC analysis was performed for all samples in the 2- to 4-ng/mL PSA range. At biopsy, 158 men had no evidence of malignancy and 57 (26.5%) were diagnosed with prostate cancer. ROC analysis indicated that the area under the curve (AUC) for cPSA was 0.64, which was statistically significantly greater than that achieved for tPSA (AUC, 0.57; P 92% of the cancers treated with radical prostatectomy were organ confined, and the histologic grading of the tumors ranged from moderately to poorly differentiated with Gleason scores from 5 to 9. These data confirm that there is a high incidence of clinically significant prostate cancer in men with tPSA levels