No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting

Francis Jacob, Meier M, Mara Meier, Mara Isabella Meier, Caduff R, Rosmarie Caduff, Goldstein D, Daniel R. Goldstein, Darlene Goldstein, Pochechueva T, Tatiana Pochechueva, Neville Hacker, Neville F. Hacker, Daniel Fink, Fink D, Viola Heinzelmann‐Schwarz, Viola Heinzelmann-Schwarz
Gynecologic Oncology · 2011 · vol. 121(3) , pp. 487–491 · doi:10.1016/j.ygyno.2011.02.022 · PMID:21420727 · W2071541869
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This study investigated the combination of HE4 and CA125 as ovarian tumor markers, noting CA125's limited sensitivity for early-stage cancers.

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The study evaluated whether combining HE4 and CA125 improves ovarian tumor marker performance in a clinical setting for epithelial ovarian cancer, noting that CA125 is more informative for peritoneally spread disease but has limited sensitivity for early cancers. Using the clinical context described in the objective, the authors found no benefit from the combined use of HE4 and CA125 compared with using markers without their combination. A key limitation stated by the study framing is that CA125’s sensitivity issues for early disease motivate marker improvement, yet the combination did not address that gap. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

OBJECTIVE: About 70% of epithelial ovarian cancer patients (EOC) are diagnosed at advanced stage with a five-year survival rate of only 30%. Whilst CA125 detects peritoneally-spread disease, it has limited sensitivity for early cancers, many of which are potentially curable. METHODS: We compared the new commercially available tumor marker HE4 with CA125 individually, in combination, within the risk of malignancy index (RMI) and the newly defined risk of malignancy algorithm (ROMA). Our prospectively-collected cohort of 160 patients consisted of healthy controls, benign diseases, and borderline tumors/adenocarcinomas of ovarian, tubal, peritoneal and endometrial origin. HE4 and CA125 were measured in serum using standardized ELISA. RESULTS: Both markers showed similar diagnostic performance in the detection of EOC at clinically defined thresholds (CA125 35U/ml; HE4 70pM) but HE4 was not elevated in endometriosis. Comparison of non-malignant diagnoses (n=71) versus early stage ovarian and tubal cancers (n=19) revealed that HE4 and ROMA displayed the best diagnostic performance (AUC 0.86/0.87, specificity 85.9%/87.3% and sensitivity 78.9%/78.9%, respectively). Whilst RMICA125 detects peritoneal cancer better than all other models (AUC 0.99, specificity 97.2%, sensitivity 80.0%), there is no other detection benefit from RMI compared to HE4 alone or included in ROMA. CONCLUSIONS: The major advantage of HE4 lies in its specificity and improved detection of borderline tumors and early stage ovarian and tubal cancers. HE4 is superior to CA125 with or without RMI and ROMA indices. However, we see no benefit from combining both markers in clinical practice.
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research article No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting 2011 Objective. About 70% of epithelial ovarian cancer patients (EOC) are diagnosed at advanced stage with a five-year survival rate of only 30%. Whilst CA125 detects peritoneally-spread disease, it has limited sensitivity for early cancers, many of which are potentially curable. Type research article Web of Science ID WOS:000291240700012 Author(s) Jacob, Francis Meier, Mara Caduff, Rosmarie Pochechueva, Tatiana Hacker, Neville Fink, Daniel Heinzelmann-Schwarz, Viola Date Issued 2011 Published in Volume 121 Start page 487 End page 491 Subjects Editorial or Peer reviewed REVIEWED Written at EPFL EPFL units Available on Infoscience December 16, 2011 Use this identifier to reference this record

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MeSH descriptors

Biomarkers, Tumor CA-125 Antigen Epididymal Secretory Proteins Membrane Proteins beta-Defensins beta-Defensins Biomarkers, Tumor Biomarkers, Tumor CA-125 Antigen CA-125 Antigen Carcinoma, Ovarian Epithelial Carcinoma, Ovarian Epithelial Cohort Studies Cohort Studies Enzyme-Linked Immunosorbent Assay Enzyme-Linked Immunosorbent Assay Epididymal Secretory Proteins Epididymal Secretory Proteins Female Female

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