Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study

Huub H van Rossum ¹, Stefan Holdenrieder ^2,3, Bart E P B Ballieux ⁴

¹Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands.
²Institute of Laboratory Medicine, Munich Biomarker Research Center, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
³INSTAND e.V., Society for Promoting Quality Assurance in Medical Laboratories, Duesseldorf, Germany.
⁴Department of Clinical Chemistry, Leiden University Medical Center, Leiden, the Netherlands.
⁵RCPA Quality Assurance Programs, St Leonards, Sydney, Australia.
⁶Department of Laboratory Medicine, Konkuk University Medical Center, Seoul, South Korea.
⁷National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China.
⁸UK NEQAS Immunology, Immunochemistry & Allergy, Northern General Hospital, Sheffield, United Kingdom.
⁹SKML, Nijmegen, the Netherlands.
¹⁰Department of Laboratory Medicine of the Radboud University Medical Center, Nijmegen, the Netherlands.
¹¹Department of Laboratory Medicine, Seoul National University Bundang Hospital and College of Medicine, Seongnam, South Korea.
¹²UK NEQAS [Edinburgh], Department of Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
¹³Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.
¹⁴Department of Laboratory Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹⁵Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
¹⁶Department of Laboratory Medicine, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

⁰Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands.

Clinical Chemistry +

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February 22, 2024

View abstract on PubMed

Summary

External quality assessment (EQA) programs reveal tumor marker (TM) harmonization status. While alpha-fetoprotein (AFP) and prostate-specific antigen (PSA) show good harmonization, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA15-3, and CA19-9 require further investigation.

Area Of Science

Clinical Chemistry
Laboratory Medicine
Biomarker Analysis

Background

The harmonization status of most tumor markers (TMs) is largely unknown.
This study investigates the feasibility of using external quality assessment (EQA) programs to assess TM harmonization.
Focus on six key TMs: alpha-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3, and CA19-9.

Purpose Of The Study

To determine the current harmonization status of six common tumor markers.
To evaluate the utility of EQA programs in providing insights into TM harmonization.
To identify specific TMs that may require further harmonization efforts.

Main Methods

Utilized EQA sample results from six international EQA providers between 2020-2021.
Calculated consensus means from common measurement procedures (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, Siemens Atellica) as reference values.
Compared relative differences of EQA sample means to consensus means against established bias criteria (minimum, desirable, optimal).

Main Results

Harmonization was within optimal bias criteria for AFP and desirable bias for PSA across all measurement procedures.
Carcinoembryonic antigen (CEA) generally met minimum bias criteria, but results <8 µg/L exceeded this threshold.
Cancer antigen 125 (CA125), CA15-3, and CA19-9 exhibited harmonization outside the minimum bias criteria, indicating systematic differences.

Conclusions

EQA programs provide valuable data on the harmonization status of key tumor markers.
While AFP and PSA demonstrate good harmonization, CEA, CA125, CA15-3, and CA19-9 require further investigation.
A pilot harmonization study for CEA, CA125, CA15-3, and CA19-9 is recommended.