PSA enzymatic activity: a new biomarker for assessing prostate cancer aggressiveness.
BACKGROUND
With the advent of widespread prostate-specific antigen (PSA) testing in recent decades, prostate cancer (PCa) has emerged as the most frequently diagnosed non-skin cancer among men in the U.S. and Europe. Greater screening rates coupled with improved detection methods have caused a controversial upsurge in the number of men undergoing prostate biopsy and subsequent treatment. However, current diagnostic techniques generally suffer from limited ability to identify which seemingly indolent cancers are biologically aggressive.


METHODS
We collected prostatic fluid from 778 post-radical prostatectomy specimens and randomly selected samples from both the clinically confirmed aggressive (n = 50) and non-aggressive (n = 50) prostate cancer populations. We measured the level of proteolytic enzyme activity of PSA (aPSA) in each sample and used receiver operating characteristic (ROC) analysis to correlate aPSA levels with prostate cancer aggressiveness.


RESULTS
We found aPSA in prostatic fluid to be inversely proportional to disease stage, such that patients with the most aggressive PCa have on average significantly reduced aPSA compared to those with less aggressive disease. Significantly, our results suggest that many (22% in our study population) of the diagnosed patients with non-aggressive PCa could have averted or delayed radical prostatectomy.


CONCLUSIONS
Given the high level of debate surrounding PSA screening effectiveness [3-5] and the recent U.S. Preventative Services Task Force recommendation to discontinue PSA screening [6], our results provide renewed hope that a clinical monitoring tool may emerge that truly refines PCa treatment decision-making.
Ohmx Corporation, Evanston, Illinois.
Michael J
MJ
Ahrens
Paul A
PA
Bertin
Edward F
EF
Vonesh
Thomas J
TJ
Meade
William J
WJ
Catalona
Dimitra
D
Georganopoulou
D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D010865:Pilot Projects; D011467:Prostate / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016037:Single-Blind Method
D015415:Biomarkers; D017430:Prostate-Specific Antigen
PSA; aggressiveness; biomarker; prostate cancer