Review
Accuracy of CA 125 in the diagnosis of ovarian tumors: A quantitative systematic review

https://doi.org/10.1016/j.ejogrb.2008.08.011Get rights and content

Abstract

A quantitative systematic review was performed to estimate the accuracy of CA 125 assay in the diagnosis of ovarian tumors. Studies that evaluated CA 125 levels for the diagnosis of ovarian tumors and compared them with paraffin-embedded sections as the diagnostic standard were included. Seventeen studies were analyzed, which included 2374 women. The pooled sensitivity for the diagnosis of borderline tumors or ovarian cancer was 0.80 (I.C. 95% 0.76–0.82) and the specificity was 0.75 (I.C. 95% 0.73–0.77). The diagnostic odds ratio for ovarian cancer and borderline lesions vs. benign lesions was 21.2 (95% C.I., 12–37). Summary receiver operating characteristic curves were constructed due to heterogeneity in the diagnostic odds ratio. For malignant and borderline ovarian tumors vs. benign lesions the area under the curve was 0.8877. A CA 125 level of ≥35 U/ml is a useful preoperative test for predicting the benign or malignant nature of pelvic masses. The accuracy of CA 125 in the diagnosis of ovarian tumors is high and very important in helping the surgeon to decide what kind of surgery should be performed.

Introduction

It is estimated that 21,650 women will be diagnosed with cancer of the ovary in 2008 and 15,520 women will die of the disease. In the years 2001–2005 the age-adjusted death rate from ovarian cancer was 8.8 per 100,000 women per year in the United States [1]. Benign, borderline, and malignant lesions have been identified within the same surgical specimen [2]. However, the frequency and velocity of progression from dysplasia into cancer remain unknown [3].

The diagnosis of ovarian neoplasms is a common problem in clinical practice. Although the majority of adnexal masses are benign, the main objective of diagnostic evaluation is to exclude or confirm the diagnosis of malignancy. The methods used for the evaluation of women with suspected adnexal masses are physical examination, ultrasound and determination of serum CA 125 levels [4]. CA 125 is an antigenic determinant of a high molecular-weight glycoprotein recognized by a monoclonal antibody (OC 125). This is expressed by epithelial ovarian tumors as well as by other tissues of Müllerian origin (peritoneum, pleura, and pericardium) [5]. A CA 125 level ≥35 U/ml is considered to indicate suspected malignancy [4]. In general, CA 125 is elevated in 80–85% of women with advanced epithelial ovarian cancer and in 65% of patients with mucinous carcinoma of the ovary [5]. However, only 50% of patients with stage I ovarian cancer will have an elevated CA 125 level [5]. The diagnostic accuracy of ovarian tumors is significantly improved by combining transvaginal ultrasound with Doppler and CA 125 findings. Using these methods together, an erroneous diagnosis may occur in only 6% of cases [6]. Magnetic resonance (MR) imaging also provides useful information on the characterization of various ovarian masses as neoplastic or non-neoplastic and, when neoplastic, on a spectrum from benign to malignant. A strategy for the diagnosis of ovarian masses with MR imaging incorporates signal intensity characteristics into morphologic characteristics [7].

We undertook a quantitative systematic review of the literature to ascertain the accuracy of CA 125 levels in the diagnosis of ovarian cancer and to explore the reasons for the ongoing controversies regarding this issue.

Section snippets

Identification of studies

A comprehensive search of the MEDLINE, CANCERLIT, LILACS, and EMBASE databases was performed for articles published between January 1985 and December 2007. The medical subject headings (MeSH) and text words for the terms “ovarian neoplasm” and “CA 125” were combined with the MeSH term diagnosis (“sensitivity and specificity”). The search was limited to studies in humans, but had no language restrictions. In addition, the Cochrane Library was searched. Reference lists of all available primary

Study identification and eligibility

The process of study selection is summarized in Fig. 1. Our initial search identified 785 potentially relevant articles. We excluded 757 published studies after reviewing their titles and abstracts, as they did not relate to the subject under review. Twenty-eight full-text articles were retrieved; 11 were excluded after further scrutiny. A complete list of excluded studies is available from the authors. Seventeen primary studies, involving 2374 women, met the criteria for inclusion and were

Discussion

In summary, this systematic review showed that levels of CA 125 of ≥35 U/ml may detect malignant or borderline ovarian tumors. However, CA 125 levels may also be elevated in benign lesions such as endometriosis, uterine myomas, acute and chronic salpingitis, and pelvic inflammatory disease. Therefore, the sensitivity for detecting malignant ovarian tumors using CA 125 levels was 80%, but the specificity was 75%. Due to the fact that the DOR was 21.2, the CA 125 level is a useful preoperative

Conflict of interest

None declared.

Contributors: L.R.M. had full access to all data and takes responsibility for the integrity and accuracy of the analysis. D.D.R., M.I.R., and M.C.B. organized the study concept and the design. L.R.M. acquired, analyzed, and interpreted the data. L.R.M., D.D.R., M.I.R., and M.C.B. drafted the manuscript. L.R.M. and D.D.R. performed the statistical analysis.

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