[-2]Proenzyme Prostate Specific Antigen for Prostate Cancer Detection: A National Cancer Institute Early Detection Research Network Validation Study

Lori J Sokoll, Yinghui Wang, Ziding Feng, Jacob Kagan, Alan Wayne Partin, Martin G. Sanda, Ian M. Thompson, Daniel Wan-Yui Chan

Research output: Contribution to journalArticle

Abstract

Purpose: This study evaluated the [-2]proenzyme prostate specific antigen serum marker using a blinded reference specimen set from 3 National Cancer Institute Early Detection Research Network centers from men with an indication for prostate biopsy. Materials and Methods: Serum was collected before biopsy from 123 men with no prior biopsy or prostate cancer history. Specimens (cancer cases 51%, noncancer controls 49%) were selected equally from the 3 sites, and analyzed for prostate specific antigen, free prostate specific antigen, [-2]proenzyme prostate specific antigen, benign prostate specific antigen and testosterone (Beckman Coulter ACCESS® analyzer). Results: There was no difference in total prostate specific antigen concentrations (noncancer 6.80 ± 5.20 ng/ml, cancer 6.94 ± 5.12 ng/ml) among the groups. Overall %[-2]proenzyme prostate specific antigen had the greatest area under the curve (AUC 0.69) followed by percent free prostate specific antigen (AUC 0.61). For %[-2]proenzyme prostate specific antigen maximal sensitivity was 60% and specificity was 70%. A logistic regression model combining prostate specific antigen, benign prostate specific antigen, percent free prostate specific antigen, %[-2]proenzyme prostate specific antigen, [-2]proenzyme prostate specific antigen/benign prostate specific antigen and testosterone had an AUC of 0.73. In the 2 to 10 ng/ml prostate specific antigen range %[-2]proenzyme prostate specific antigen and the model had the largest AUC (0.73). The AUC for percent free prostate specific antigen was 0.53. Specificities for %[-2]proenzyme prostate specific antigen, the logistic regression model and percent free prostate specific antigen at 90% sensitivity were 41%, 32% and 18%, and at 95% sensitivity were 31%, 26% and 16%, respectively. Conclusions: %[-2]proenzyme prostate specific antigen was the best predictor of prostate cancer detection compared to percent free prostate specific antigen, particularly in the 2 to 10 ng/ml total prostate specific antigen range. These findings provide a rationale for broader validation studies to determine whether %[-2]proenzyme prostate specific antigen alone can replace other molecular prostate specific antigen assays (such as percent free prostate specific antigen) for improving the accuracy of prostate cancer early detection. These findings also support the usefulness of well characterized, carefully collected reference sets to evaluate new biomarkers.

Original languageEnglish (US)
Pages (from-to)539-543
Number of pages5
JournalJournal of Urology
Volume180
Issue number2
DOIs
StatePublished - Aug 2008

Fingerprint

Enzyme Precursors
National Cancer Institute (U.S.)
Validation Studies
Prostate-Specific Antigen
Prostatic Neoplasms
Research
Area Under Curve
Logistic Models
Biopsy
Testosterone

Keywords

  • biological
  • early diagnosis
  • prostate-specific antigen
  • prostatic neoplasms
  • tumor markers

ASJC Scopus subject areas

  • Urology

Cite this

[-2]Proenzyme Prostate Specific Antigen for Prostate Cancer Detection : A National Cancer Institute Early Detection Research Network Validation Study. / Sokoll, Lori J; Wang, Yinghui; Feng, Ziding; Kagan, Jacob; Partin, Alan Wayne; Sanda, Martin G.; Thompson, Ian M.; Chan, Daniel Wan-Yui.

In: Journal of Urology, Vol. 180, No. 2, 08.2008, p. 539-543.

Research output: Contribution to journalArticle

@article{fb34f755e63b42a0924c701eaf229609,
title = "[-2]Proenzyme Prostate Specific Antigen for Prostate Cancer Detection: A National Cancer Institute Early Detection Research Network Validation Study",
abstract = "Purpose: This study evaluated the [-2]proenzyme prostate specific antigen serum marker using a blinded reference specimen set from 3 National Cancer Institute Early Detection Research Network centers from men with an indication for prostate biopsy. Materials and Methods: Serum was collected before biopsy from 123 men with no prior biopsy or prostate cancer history. Specimens (cancer cases 51{\%}, noncancer controls 49{\%}) were selected equally from the 3 sites, and analyzed for prostate specific antigen, free prostate specific antigen, [-2]proenzyme prostate specific antigen, benign prostate specific antigen and testosterone (Beckman Coulter ACCESS{\circledR} analyzer). Results: There was no difference in total prostate specific antigen concentrations (noncancer 6.80 ± 5.20 ng/ml, cancer 6.94 ± 5.12 ng/ml) among the groups. Overall {\%}[-2]proenzyme prostate specific antigen had the greatest area under the curve (AUC 0.69) followed by percent free prostate specific antigen (AUC 0.61). For {\%}[-2]proenzyme prostate specific antigen maximal sensitivity was 60{\%} and specificity was 70{\%}. A logistic regression model combining prostate specific antigen, benign prostate specific antigen, percent free prostate specific antigen, {\%}[-2]proenzyme prostate specific antigen, [-2]proenzyme prostate specific antigen/benign prostate specific antigen and testosterone had an AUC of 0.73. In the 2 to 10 ng/ml prostate specific antigen range {\%}[-2]proenzyme prostate specific antigen and the model had the largest AUC (0.73). The AUC for percent free prostate specific antigen was 0.53. Specificities for {\%}[-2]proenzyme prostate specific antigen, the logistic regression model and percent free prostate specific antigen at 90{\%} sensitivity were 41{\%}, 32{\%} and 18{\%}, and at 95{\%} sensitivity were 31{\%}, 26{\%} and 16{\%}, respectively. Conclusions: {\%}[-2]proenzyme prostate specific antigen was the best predictor of prostate cancer detection compared to percent free prostate specific antigen, particularly in the 2 to 10 ng/ml total prostate specific antigen range. These findings provide a rationale for broader validation studies to determine whether {\%}[-2]proenzyme prostate specific antigen alone can replace other molecular prostate specific antigen assays (such as percent free prostate specific antigen) for improving the accuracy of prostate cancer early detection. These findings also support the usefulness of well characterized, carefully collected reference sets to evaluate new biomarkers.",
keywords = "biological, early diagnosis, prostate-specific antigen, prostatic neoplasms, tumor markers",
author = "Sokoll, {Lori J} and Yinghui Wang and Ziding Feng and Jacob Kagan and Partin, {Alan Wayne} and Sanda, {Martin G.} and Thompson, {Ian M.} and Chan, {Daniel Wan-Yui}",
year = "2008",
month = "8",
doi = "10.1016/j.juro.2008.04.015",
language = "English (US)",
volume = "180",
pages = "539--543",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - [-2]Proenzyme Prostate Specific Antigen for Prostate Cancer Detection

T2 - A National Cancer Institute Early Detection Research Network Validation Study

AU - Sokoll, Lori J

AU - Wang, Yinghui

AU - Feng, Ziding

AU - Kagan, Jacob

AU - Partin, Alan Wayne

AU - Sanda, Martin G.

AU - Thompson, Ian M.

AU - Chan, Daniel Wan-Yui

PY - 2008/8

Y1 - 2008/8

N2 - Purpose: This study evaluated the [-2]proenzyme prostate specific antigen serum marker using a blinded reference specimen set from 3 National Cancer Institute Early Detection Research Network centers from men with an indication for prostate biopsy. Materials and Methods: Serum was collected before biopsy from 123 men with no prior biopsy or prostate cancer history. Specimens (cancer cases 51%, noncancer controls 49%) were selected equally from the 3 sites, and analyzed for prostate specific antigen, free prostate specific antigen, [-2]proenzyme prostate specific antigen, benign prostate specific antigen and testosterone (Beckman Coulter ACCESS® analyzer). Results: There was no difference in total prostate specific antigen concentrations (noncancer 6.80 ± 5.20 ng/ml, cancer 6.94 ± 5.12 ng/ml) among the groups. Overall %[-2]proenzyme prostate specific antigen had the greatest area under the curve (AUC 0.69) followed by percent free prostate specific antigen (AUC 0.61). For %[-2]proenzyme prostate specific antigen maximal sensitivity was 60% and specificity was 70%. A logistic regression model combining prostate specific antigen, benign prostate specific antigen, percent free prostate specific antigen, %[-2]proenzyme prostate specific antigen, [-2]proenzyme prostate specific antigen/benign prostate specific antigen and testosterone had an AUC of 0.73. In the 2 to 10 ng/ml prostate specific antigen range %[-2]proenzyme prostate specific antigen and the model had the largest AUC (0.73). The AUC for percent free prostate specific antigen was 0.53. Specificities for %[-2]proenzyme prostate specific antigen, the logistic regression model and percent free prostate specific antigen at 90% sensitivity were 41%, 32% and 18%, and at 95% sensitivity were 31%, 26% and 16%, respectively. Conclusions: %[-2]proenzyme prostate specific antigen was the best predictor of prostate cancer detection compared to percent free prostate specific antigen, particularly in the 2 to 10 ng/ml total prostate specific antigen range. These findings provide a rationale for broader validation studies to determine whether %[-2]proenzyme prostate specific antigen alone can replace other molecular prostate specific antigen assays (such as percent free prostate specific antigen) for improving the accuracy of prostate cancer early detection. These findings also support the usefulness of well characterized, carefully collected reference sets to evaluate new biomarkers.

AB - Purpose: This study evaluated the [-2]proenzyme prostate specific antigen serum marker using a blinded reference specimen set from 3 National Cancer Institute Early Detection Research Network centers from men with an indication for prostate biopsy. Materials and Methods: Serum was collected before biopsy from 123 men with no prior biopsy or prostate cancer history. Specimens (cancer cases 51%, noncancer controls 49%) were selected equally from the 3 sites, and analyzed for prostate specific antigen, free prostate specific antigen, [-2]proenzyme prostate specific antigen, benign prostate specific antigen and testosterone (Beckman Coulter ACCESS® analyzer). Results: There was no difference in total prostate specific antigen concentrations (noncancer 6.80 ± 5.20 ng/ml, cancer 6.94 ± 5.12 ng/ml) among the groups. Overall %[-2]proenzyme prostate specific antigen had the greatest area under the curve (AUC 0.69) followed by percent free prostate specific antigen (AUC 0.61). For %[-2]proenzyme prostate specific antigen maximal sensitivity was 60% and specificity was 70%. A logistic regression model combining prostate specific antigen, benign prostate specific antigen, percent free prostate specific antigen, %[-2]proenzyme prostate specific antigen, [-2]proenzyme prostate specific antigen/benign prostate specific antigen and testosterone had an AUC of 0.73. In the 2 to 10 ng/ml prostate specific antigen range %[-2]proenzyme prostate specific antigen and the model had the largest AUC (0.73). The AUC for percent free prostate specific antigen was 0.53. Specificities for %[-2]proenzyme prostate specific antigen, the logistic regression model and percent free prostate specific antigen at 90% sensitivity were 41%, 32% and 18%, and at 95% sensitivity were 31%, 26% and 16%, respectively. Conclusions: %[-2]proenzyme prostate specific antigen was the best predictor of prostate cancer detection compared to percent free prostate specific antigen, particularly in the 2 to 10 ng/ml total prostate specific antigen range. These findings provide a rationale for broader validation studies to determine whether %[-2]proenzyme prostate specific antigen alone can replace other molecular prostate specific antigen assays (such as percent free prostate specific antigen) for improving the accuracy of prostate cancer early detection. These findings also support the usefulness of well characterized, carefully collected reference sets to evaluate new biomarkers.

KW - biological

KW - early diagnosis

KW - prostate-specific antigen

KW - prostatic neoplasms

KW - tumor markers

UR - http://www.scopus.com/inward/record.url?scp=46449132555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46449132555&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2008.04.015

DO - 10.1016/j.juro.2008.04.015

M3 - Article

C2 - 18550118

AN - SCOPUS:46449132555

VL - 180

SP - 539

EP - 543

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 2

ER -