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Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer: Updated Guidelines From the European Group on Tumor Markers
  1. György Sölétormos, MD, DMSc*,
  2. Michael J. Duffy, MD, PhD,
  3. Suher Othman Abu Hassan, MD*,
  4. René H.M. Verheijen, MD, PhD,
  5. Bengt Tholander, MD, PhD§,
  6. Robert C. Bast, MD, PhD,
  7. Katja N. Gaarenstroom, MD, PhD,
  8. Catharine M. Sturgeon, MD, PhD#,
  9. Johannes M. Bonfrer, MD, PhD**,
  10. Per Hyltoft Petersen, Msc††,
  11. Hugo Troonen, PhD, MSc‡‡,
  12. Gian CarloTorre, MD, PhD§§,
  13. Jan Kanty Kulpa, MD, PhD∥∥,
  14. Malgorzata K. Tuxen, MD, PhD¶¶ and
  15. Raphael Molina, MD, PhD##
  1. *Department of Clinical Biochemistry, University of Copenhagen North Zealand Hospital, Hillerød, Denmark;
  2. Clinical Research Centre, St Vincent’s University Hospital and UCD School of Medicine and Medical Science, Conway Institute of Bimolecular and Biomedical, Research, University College Dublin, Dublin, Ireland;
  3. Department of Gynecological Oncology, University Medical, Centre Utrecht, Utrecht, the Netherlands;
  4. §Department of Oncology, Gynecologic Oncology Unit, Uppsala, University Hospital, Uppsala, Sweden;
  5. Division of Cancer Medicine, Department of Gynecologic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX;
  6. Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands;
  7. #Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom;
  8. **Senior Expert Clinical Laboratories, PUM Netherlands Senior Experts, Heemstede, the Netherlands;
  9. ††Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Section for General Practice, University of Bergen, Bergen, Norway;
  10. ‡‡Emeritus Scientist from Abbott, Limburg, Germany;
  11. §§Consultant, Centro Ippocrate, Bogliasco, Italy;
  12. ∥∥Department of Clinical Biochemistry, Center of Oncology - M. Sklodowska-Curie Memorial Institute, Cracow Division, Poland;
  13. ¶¶Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark; and
  14. ##Laboratory of Biochemistry, Hospital Clinico, Barcelona, Spain.
  1. Address correspondence and reprint requests to György Sölétormos, MD, DMSc, Department of Clinical Biochemistry, University of Copenhagen North Zealand Hospital, Dyrehavevej 29, DK-3400, Hillerød, Denmark. E-mail:


Objective To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer.

Methods Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation.

Results Because of its low sensitivity (50–62% for early stage epithelial ovarian cancer) and limited specificity (94–98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery.

Conclusions At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.

  • Ovarian cancer
  • CA125
  • HE4
  • Screening
  • Differential diagnosis
  • Monitoring

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  • R.C.B. receives royalties for CA125 from Fujirebio Diagnostics Inc. and serves on the Scientific Advisory Board of Vermillion.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.