Letter to the Editor

Critical Analysis of False Elevations in PSAResults Reported With the Abbott AxSYM Assay

In 1998, it is estimated that 184,000 new prostatecancer cases will be diagnosed [1], a decrease from210,000 cases estimated (revised estimate) in 1997 [2].Recent declines in prostate cancer incidence, followingprevious appreciable increases, and increased survivalrates have been attributed in part to increased detec-tion and earlier diagnoses resulting from PSA testing.Early detection of prostate cancer increases the prob-ability of organ confined cancers which can be suc-cessfully treated by radical prostatectomy. Between1974 and 1993, the percentage of men selecting radicalprostatectomy as a treatment option increased from9% of patients to 29% of patients [3].

Following surgery, PSA concentrations are ex-pected to reach undetectable concentrations if all pros-tatic tissue was surgically removed [4]. Detectablepost-prostatectomy PSA concentrations are indicativeof local disease recurrence or distant metastases [5],therefore falsely elevated results could be misleadingand result in unnecessary invasive testing and in-creased anxiety by both the patient and the treatingphysician [6].

In a product communication, Abbott Laboratoriesnotified users of the AxSYM and IMx PSA assays thatdue to non-specific binding, falsely elevated PSA con-centrations had been observed with specific PSA re-agent lots [7]. These false elevations were primarilyobserved in specimens from post-radical prostatec-tomy patients. The product communication issued byAbbott indicated that suspect lots of reagent had beenin clinical use for the previous 4 months. It was rec-ommended that the following disclaimer be includedwith patient results: ‘‘A PSA value in the range of 0.1to 0.6 ng/mL is indeterminate if being used as an in-dicator of recurrent or residual disease [7].’’

The Abbott Product Communication also indicatedthat the cause of the non-specific binding had beenidentified and resolved and that results from subse-quent reagent lots would not require the precaution-ary statement. This study was conducted to determineif the non-specific binding that caused false elevationsof PSA was resolved with current AxSYM PSA re-agents because the AxSYM PSA assay is performed ata physicians’ group practice laboratory (AmbulatoryCare Laboratory) affiliated with The Johns Hopkins

Bayview Medical Center. It is notable that 70% of labo-ratories participating in the 1997 CAP Ligand Surveyutilized either the AxSYM or IMx assays [8]. We com-pared AxSYM PSA results to Tosoh AIA-1200DX (To-soh Medics, Foster City, CA) and Hybritech Tan-dem-R methods (Beckman, San Diego, CA) on thesame samples. We previously confirmed that suspectreferral patient specimens analyzed in other laborato-ries with detectable concentrations by the Abbottmethods were undetectable when measured using ourcentral laboratory method (Tosoh). Specimens for thisstudy consisted of 48 random and 19 post-radicalprostatectomy specimens previously analyzed in ourcentral laboratory by Tosoh and Tandem-R methodsand 30 random specimens collected prospectively inour Ambulatory Care Laboratory where the AxSYMPSA assay is performed. Of the 97 specimens, 55 had

Fig. 1. Relationships between Abbott AxSYM PSA and HybritechTandem-R PSA concentrations (top panel) and Abbott AxSYM PSAand Tosoh PSA concentrations (bottom panel) in 42 specimens.

The Prostate 38:79–80 (1999)

© 1999 Wiley-Liss, Inc.

original PSA concentrations that were undetectable(<0.1 ng/mL), 40 specimens had PSA concentrationsù0.1 ng/mL, and 2 specimens had not been analyzedfor PSA. In this study specimens were analyzed on thesame day by all three methods.

The 55 specimens previously determined to haveundetectable PSA concentrations were all undetect-able by the AxSYM, Tosoh, and Tandem-R methodswhen reanalyzed. Detectable PSA concentrations(ù0.1 ng/mL) were observed with both the Tosoh andHybritech methods in the 19 specimens that were be-tween 0.1 and 0.6 ng/mL by the AxSYM assay. Resultscomparing the 42 specimens with PSA concentrationsù0.1 ng/mL showed excellent correlation (r = 0.99)between methods (Fig. 1). Small biases between thethree methods are most likely due to calibration, an-tibody, and/or assay design differences.

In summary, the results from this experiment com-paring the Abbott AxSYM PSA assay to the Tosoh andHybritech Tandem-R assays indicated no non-specificbinding problems with the specific lot of AxSYM re-agent used for this study.

ACKNOWLEDGMENTS

This study was supported in part by Abbott Labo-ratories.

Lori J. Sokoll1

Alan W. Partin2

Joel B. Nelson2

Daniel W. Chan1,2

Departments of Pathology1 and Urology2

The Johns Hopkins Medical InstitutionsBaltimore, MD

REFERENCES

1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics,1998. CA Cancer J Clin 1998;48:6–29.

2. Wingo PA, Landis S, Ries LAG. An adjustment to the 1997 es-timate for new prostate cancer cases. CA Cancer J Clin 1997;47:239–42.

3. Mettlin C. Changes in patterns of prostate cancer care in theUnited States: results of American College of Surgeons Com-mission on Cancer Studies, 1974–1993: Prostate 1997;32:221–6.

4. Chan DW, Sokoll LJ. Prostate-specific antigen: update 1997. J IntFed Clin Chem 1997;9:120–5.

5. Partin AW, Oesterling JE. The clinical usefulness of prostatespecific antigen: update 1994. J Urol 1994;152:1358–68.

6. Walsh PC. Editorial comment. J Urol 1997;158:1620–1.

7. Product Communication, Abbott Laboratories, March, 1997.

8. Participant summary, Ligand assay-general survey 1997 SetK-B. College of American Pathologists. 1997:16–17.

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