Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer.

INTRODUCTION: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively]. METHODS: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4-10 microg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. RESULTS: The proPSA forms had quantification limits of 0.015-0.025 microg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64-0.74), 0.64 (0.58-0.68), 0.63 (0.58-0.68), and 0.57 (0.51-0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66-0.86), with 90% sensitivity and 36% specificity at 0.04 microg/L. CONCLUSIONS: The percentage of proPSA gave better cancer detection in the 4-10 microg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.

Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml.

PURPOSE: Pro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml. MATERIALS AND METHODS: Research use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221). RESULTS: In PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001). CONCLUSIONS: The %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.