Clinical interpretation of prostate-specific antigen values: type of applied cut-off value exceeds methods bias as the major source of variation

Lieke J.J. Klinkenberg (Corresponding author), Eef G.W.M. Lentjes, Arjen Kars Boer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods: The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results: In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86–93% versus 79% range 63–95%, respectively). Conclusions: This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalAnnals of Clinical Biochemistry
Volume56
Issue number2
DOIs
Publication statusPublished - 1 Mar 2019

Fingerprint

Prostate-Specific Antigen
Prostatic Neoplasms
Biopsy
Linear regression
Standardization
Decision making
Netherlands
Prostate
Linear Models
Monitoring
Sensitivity and Specificity

Keywords

  • cut-off value
  • external quality assessment scheme
  • prostate cancer
  • Prostate-specific antigen

Cite this

@article{bf33f195df77402fbd2da07599f1482f,
title = "Clinical interpretation of prostate-specific antigen values: type of applied cut-off value exceeds methods bias as the major source of variation",
abstract = "Background: Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods: The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results: In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67{\%} of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26{\%}, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217{\%}. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89{\%} range 86–93{\%} versus 79{\%} range 63–95{\%}, respectively). Conclusions: This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.",
keywords = "cut-off value, external quality assessment scheme, prostate cancer, Prostate-specific antigen",
author = "Klinkenberg, {Lieke J.J.} and Lentjes, {Eef G.W.M.} and Boer, {Arjen Kars}",
year = "2019",
month = "3",
day = "1",
doi = "10.1177/0004563218822665",
language = "English",
volume = "56",
pages = "259--265",
journal = "Annals of Clinical Biochemistry",
issn = "0004-5632",
publisher = "SAGE Publications Ltd",
number = "2",

}

Clinical interpretation of prostate-specific antigen values : type of applied cut-off value exceeds methods bias as the major source of variation. / Klinkenberg, Lieke J.J. (Corresponding author); Lentjes, Eef G.W.M.; Boer, Arjen Kars.

In: Annals of Clinical Biochemistry, Vol. 56, No. 2, 01.03.2019, p. 259-265.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Clinical interpretation of prostate-specific antigen values

T2 - type of applied cut-off value exceeds methods bias as the major source of variation

AU - Klinkenberg, Lieke J.J.

AU - Lentjes, Eef G.W.M.

AU - Boer, Arjen Kars

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background: Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods: The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results: In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86–93% versus 79% range 63–95%, respectively). Conclusions: This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.

AB - Background: Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods: The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results: In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86–93% versus 79% range 63–95%, respectively). Conclusions: This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.

KW - cut-off value

KW - external quality assessment scheme

KW - prostate cancer

KW - Prostate-specific antigen

UR - http://www.scopus.com/inward/record.url?scp=85061966700&partnerID=8YFLogxK

U2 - 10.1177/0004563218822665

DO - 10.1177/0004563218822665

M3 - Article

C2 - 30798616

AN - SCOPUS:85061966700

VL - 56

SP - 259

EP - 265

JO - Annals of Clinical Biochemistry

JF - Annals of Clinical Biochemistry

SN - 0004-5632

IS - 2

ER -