Abstract
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).
Design, setting, and participants
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.
Measurements
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).
Results and limitations
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).
Keywords
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References
- Benign prostate-specific antigen (BPSA) in serum is increased in benign prostate disease.Clin Chem. 2003; 49: 253-259
- A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer.Cancer Res. 2001; 61: 6958-6963
- Seminal plasma contains “BPSA” a molecular form of prostate-specific antigen that is associated with benign prostatic hyperplasia.Prostate. 2000; 45: 271-276
- A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue.Cancer Res. 2000; 60: 756-759
- “BPSA” a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia.Urology. 2000; 55: 41-45
- Identification of precursor forms of free prostate-specific antigen in serum of prostate cancer patients by immunosorption and mass spectrometry.Cancer Res. 2001; 61: 957-962
- 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.J Urol. 2003; 170: 2181-2185
- Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer.Clin Chem. 2004; 50: 1017-1025
- Volume-based evaluation of serum assays for new prostate-specific antigen isoforms in the detection of prostate cancer.Urology. 2004; 63: 492-498
- Evaluation of precursor prostate-specific antigen isoform ratios in the detection of prostate cancer.Urol Oncol. 2005; 23: 16-21
- [-2]proenzyme prostate specific antigen for prostate cancer detection: a national cancer institute early detection research network validation study.J Urol. 2008; 180 (discussion 543): 539-543
- A [-2]proPSA-based artificial neural network significantly improves differentiation between prostate cancer and benign prostatic diseases.Prostate. 2009; 69: 198-207
- Serum BPSA outperforms both total PSA and free PSA as a predictor of prostatic enlargement in men without prostate cancer.Urology. 2004; 63 (discussion 910–1): 905-910
- Benign prostatic hyperplasia-associated free prostate-specific antigen improves detection of prostate cancer in an artificial neural network.Urology. 2009; 74: 873-877
- Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen.J Urol. 2004; 171: 2239-2244
- Additional use of [-2] precursor prostate-specific antigen and “benign” PSA at diagnosis in screen-detected prostate cancer.Urology. 2005; 65: 926-930
- Screening and prostate-cancer mortality in a randomized European study.N Engl J Med. 2009; 360: 1320-1328
- Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome, incidence and mortality.BJU Int. 2008; 101: 809-816
- Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk.Prostate. 2005; 64: 240-245
- Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.Biometrics. 1988; 44: 837-845
- Results of a randomized, population-based study of biennial screening using serum prostate-specific antigen measurement to detect prostate carcinoma.Cancer. 2004; 100: 1397-1405
- Cancer detection and cancer characteristics in the European Randomized Study of Screening for Prostate Cancer (ERSPC) – Section Rotterdam. A comparison of two rounds of screening.Eur Urol. 2007; 52: 89-97
- Tumor characteristics and prognostic factors in two subsequent screening rounds with four-year interval within prostate cancer screening trial. ERSPC Rotterdam.Urology. 2006; 68: 615-620
Article Info
Publication History
Published online: February 15, 2010
Accepted:
February 3,
2010
Received:
October 27,
2009
Footnotes
☆Please visit www.eu-acme.org/europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.
Identification
Copyright
© 2010 European Association of Urology. Published by Elsevier Inc. All rights reserved.

