Prostate-specific antigen (PSA) isoform p2PSA in combination with total PSA and free PSA improves diagnostic accuracy in prostate cancer detection.
BACKGROUND
Novel markers for prostate cancer (PCa) detection are needed. Total prostate-specific antigen (tPSA) and percent free prostate-specific antigen (%fPSA=tPSA/fPSA) lack diagnostic specificity.


OBJECTIVE
To evaluate the use of prostate-specific antigen (PSA) isoforms p2PSA and benign prostatic hyperplasia-associated PSA (BPHA).


METHODS
Our study included 405 serum samples from the Rotterdam arm of the European Randomised Study of Screening for Prostate Cancer and 351 samples from the Urology Department of Innsbruck Medical University.


METHODS
BPHA, tPSA, fPSA, and p2PSA levels were measured by Beckman-Coulter Access Immunoassay. In addition, the Beckman Coulter Prostate Health Index was calculated: phi=(p2PSA/fPSA)×√(tPSA).


CONCLUSIONS
The p2PSA and phi levels differed significantly between men with and without PCa. No difference in BPHA levels was observed. The highest PCa predictive value in both cohorts was achieved by phi with areas under the curve (AUCs) of 0.750 and 0.709, a significant increase compared to tPSA (AUC: 0.585 and 0.534) and %fPSA (AUC: 0.675 and 0.576). Also, %p2PSA (p2PSA/fPSA) showed significantly higher AUCs compared to tPSA and %fPSA (AUC: 0.716 and 0.695, respectively). At 95% and 90% sensitivity, the specificities of phi were 23% and 31% compared to 10% and 8% for tPSA, respectively. In both cohorts, multivariate analysis showed a significant increase in PCa predictive value after addition of p2PSA to a model consisting of tPSA and fPSA (increase in AUC from 0.675 to 0.755 and from 0.581 to 0.697, respectively). Additionally, the specificity at 95% sensitivity increased from 8% to 24% and 7% to 23%, respectively. Furthermore, %p2PSA, phi, and the model consisting of tPSA and fPSA with or without the addition of p2PSA missed the least of the tumours with a biopsy or pathologic Gleason score ≥7 at 95% and 90% sensitivity.


CONCLUSIONS
This study shows significant increases in PCa predictive value and specificity of phi and %p2PSA compared to tPSA and %fPSA. p2PSA has limited additional value in identifying aggressive PCa (Gleason score ≥7).
Jansen
Flip H
FH
Department of Urology, Erasmus MC, Rotterdam, The Netherlands. f.h.jansen@erasmusmc.nl
van Schaik
Ron H N
RH
Kurstjens
Joep
J
Horninger
Wolfgang
W
Klocker
Helmut
H
Bektic
Jasmin
J
Wildhagen
Mark F
MF
Roobol
Monique J
MJ
Bangma
Chris H
CH
Bartsch
Georg
G
D000368:Aged; D019540:Area Under Curve; D006305:Health Status Indicators; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis*; D012372:ROC Curve; D012044:Regression Analysis; D018709:Statistics, Nonparametric
D017430:Prostate-Specific Antigen