Advertisement

Tumor Biology

, Volume 35, Issue 3, pp 1867–1873 | Cite as

Variability of assay methods for total and free PSA after WHO standardization

  • L. Foj
  • X Filella
  • J. Alcover
  • J. M. Augé
  • J. M. Escudero
  • R. Molina
Research Article

Abstract

The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial assays has been suggested to be decreased by calibration to World Health Organization (WHO) reference materials. To characterize the current situation, it is necessary to know its impact in the critical cutoffs used in clinical practice. In the present study, we tested 167 samples with tPSA concentrations of 0 to 20 μg/L using seven PSA and six fPSA commercial assays, including Access, ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200, in which we only measured tPSA. tPSA and fPSA were measured in Access using the Hybritech and WHO calibrators. Passing–Bablok analysis was performed for PSA, and percentage of fPSA with the Hybritech-calibrated access comparison assay. For tPSA, relative differences were more than 10 % at 0.2 μg/L for ARCHITECT i2000, and at a critical concentration of 3, 4, and 10 μg/L, the relative difference was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at a critical concentration of 10 %, the 10 % relative difference limit was exceeded by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative difference limit. We have shown significant discordances between assays included in this study despite advances in standardization conducted in the last years. Further harmonization efforts are required in order to obtain a complete clinical concordance.

Keywords

Prostate cancer PSA free PSA WHO PSA standards 

References

  1. 1.
    Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 2008;8:268–78.PubMedCrossRefGoogle Scholar
  2. 2.
    Heidenreich A, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Roddam AW, Duffy MJ, Hamdy FC, et al. Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2–10 ng/ml: systematic review and meta-analysis. Eur Urol. 2005;48:386–99.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee R, Localio AR, Armstrong K, Free PSA Study Group, et al. A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology. 2006;67:762–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Semjonow A, Brandt B, Oberpenning F, Roth S, Hertle L. Discordance of assay methods creates pitfalls for the interpretation of prostate-specific antigen values. Prostate Suppl. 1996;7:3–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Stamey TA. Second Stanford conference on international standardization of prostate-specific antigen immunoassays: September 1 and 2, 1994. Urology. 1995;45:173–84.PubMedCrossRefGoogle Scholar
  7. 7.
    Stephan C, Klaas M, Muller C, Schnorr D, Loening SA, Jung K. Interchangeability of measurements of total and free prostate-specific antigen in serum with 5 frequently used assay combinations: an update. Clin Chem. 2006;52:59–64.PubMedCrossRefGoogle Scholar
  8. 8.
    Kort S, Martens F, Vanpoucke H, et al. Comparison of 6 automated assays for total and free prostate-specific antigen with special reference to their reactivity toward the WHO 96/670 reference preparation. Clin Chem. 2006;52:1568–74.PubMedCrossRefGoogle Scholar
  9. 9.
    Slev PR, La'ulu SL, Roberts WL. Intermethod differences in results for total PSA, free PSA, and percentage of free PSA. Am J Clin Pathol. 2008;129:952–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Stephan C, Köpke T, Semjonow A, et al. Discordant total and free prostate-specific antigen (PSA) assays: does calibration with WHO reference materials diminish the problem? Clin Chem Lab Med. 2009;47:1325–31.PubMedCrossRefGoogle Scholar
  11. 11.
    Forde JC, Marignol L, Blake O, et al. Standardization of assay methods reduces variability of total PSA measurements: an Irish study. BJU Int. 2012;110:644–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Roddam AW, Rimmer J, Nickerson C, Ward AM. Prostate-specific antigen: bias and molarity of commercial assays for PSA in use in England. Ann Clin Biochem. 2006;43(Pt 1):35–48.PubMedCrossRefGoogle Scholar
  13. 13.
    Roddam AW, Price CP, Allen NE, Ward AM. Assessing the clinical impact of prostate-specific antigen assay variability and nonequimolarity: a simulation study based on the population of the United Kingdom. Clin Chem. 2004;50:1012–6.PubMedCrossRefGoogle Scholar
  14. 14.
    American Urological Association. Prostate-Specific Antigen Best Practice Statement: 2009 update. http://www.auanet.org/content/guidelines-andquality-care/clinical-guidelines/mainreports/psa09.pdf (2009). Accessed 26 Jan 2013.
  15. 15.
    Myrtle JF, Klimley PG, Ivor LP, Bruni JF. Clinical utility of prostate specific antigen in the management of prostate cancer. Advances in Cancer Diagnostics. San Diego: Hybritech, Inc; 1986.Google Scholar
  16. 16.
    Catalona WJ, Richie JP, deKernion JB, et al. Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves. J Urol. 1994;152:2031–6.PubMedGoogle Scholar
  17. 17.
    Andriole GL, Crawford ED, Grubb 3rd RL, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310–9.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Jansen FH, Roobol M, Bangma CH, van Schaik RH. Clinical impact of new prostate-specific antigen WHO standardization on biopsy rates and cancer detection. Clin Chem. 2008;54:1999–2006.PubMedCrossRefGoogle Scholar
  20. 20.
    Cookson MS, Aus G, Burnett AL, et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol. 2007;177:540–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Stephan C. WHO standarization of PSA tests: clinical consequences. Nat Rev Urol. 2009;6:303–5.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • L. Foj
    • 1
  • X Filella
    • 1
  • J. Alcover
    • 2
  • J. M. Augé
    • 1
  • J. M. Escudero
    • 1
  • R. Molina
    • 1
  1. 1.Department of Biochemistry and Molecular Genetics (CDB), Hospital ClínicIDIBAPSBarcelonaSpain
  2. 2.Department of Urology, Hospital ClínicIDIBAPSBarcelonaSpain

Personalised recommendations