PSA isoforms in prostate cancer detection

Objectives: To give an overview on PSA isoforms that might help to improve specificity in Prostate Cancer (PCa) diagnosis. Methods: The authors review all the recent papers dealing with the effectiveness of PSA isoforms to improve the diagnosis potential of total PSA: percentage of free PSA (%fPSA) complexed PSA (cPSA), ProPSA, BPSA. Results: 10 to 30% of PSA is free in the serum and composed of various isoforms. It is composed of 3 distinct isoforms: ProPSA, BPSA and iPSA (for "intact PSA" which decreases with cancer). With the use of a single cut-off value of 25%, %fPSA specificity can be increased by 30% while maintaining 95% sensitivity. But free PSA measurement has limitations: namely specimen handling, assay variation and uncertainty about the appropriate reflex range. European and American multiinstitutional studies of cPSA have shown that this isoform has similar sensitivity and specificity values as %fPSA and that both perform better than total PSA in a PSA range of 2-10 ng/ml. The precursor form of PSA (pro-PSA), especially its truncated (-2) form is significantly increased in PCa patients. However, so far no study has showed for low PSA range an advantage of (-5, -7) proPSA over %fPSA. BPSA is still under investigation and reports on its clinical interest are still awaited. Conclusions: The performance of total serum PSA still needs to be improved. Several studies show potential clinical interest of PSA isoforms to improve specificity in PCa diagnosis. These preliminary results have to be confirmed especially with the most recently used isoforms: proPSA and BPSA. (c) 2006 Published by Elsevier B.V.