Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer

Abstract

BPSA and proPSA are distinct molecular forms of free PSA in serum. BPSA is a form of free PSA that is associated with BPH. The inactive precursor of PSA, proPSA, is associated with prostate tumors. ProPSA is comprised of native proPSA as well as truncated proPSA forms, [-2]pPSA and [-4]pPSA, which have been shown to be more cancer-associated than native proPSA. We have developed highly specific and sensitive research immunoassays for BPSA, and the different forms of proPSA. Free PSA in prostate cancer serum contains a median of 28% BPSA and 32% proPSA, though each form of PSA can range from 0 to more than 50% in individual samples. Early studies revealed that proPSA significantly increases the specificity for prostate cancer, especially in the 2-4 ng/ml PSA range. It is estimated that 20-30% of men with PSA values from 2-4 ng/ml have prostate cancer. In the 2.5-4 ng/ml PSA range proPSA gave a receiver operating characteristic-area under the curve (ROC-AUC) of 0.636 compared with free PSA (0.506) and complex PSA (0.509). At 90% sensitivity the specificity for proPSA was 25% compared to 10% for %FPSA and cPSA (P = < 0.001). ProPSA was superior to %FPSA and complexed PSA in the 4-10 ng/ml PSA range (AUC = 0.689, 0.637 and 0.538, respectively). ProPSA represents a more cancer-specific form of PSA that better discriminates prostate cancer from BPH.