Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: Relevance for early detection of ovarian cancer

Abstract

To investigate the sensitivity of the CA 125 immunoradiometric assay for occult ovarian neoplasia, serum CA 125 levels were retrospectively determined "blind" in specimens collected from 105 women who subsequently developed ovarian neoplasia, and from 323 matched controls. The distribution of CA 125 levels was very different between the case and control populations (p = 0.0001) over the entire collection-to-diagnosis interval (range 1-143 months). Median CA 125 levels for all cases, and for those collected more than 24, 36 or even 60 months prior to diagnosis, were always 18 U/ml or greater, compared with a median of 10.9 U/ml for controls. Half of the cases collected within the 18 months preceding diagnosis had CA 125 levels of more than 30 U/ml and one-third had levels greater than 65 U/ml. About one-fourth of those collected prior to 60 months before diagnosis had levels above 30 U/ml. In contrast, approximately 7% and 0.9% of controls had levels in excess of 30 or 65 U/ml, respectively. Elevations occurred in cases eventually diagnosed with localized or advanced cancer, and with borderline or obviously malignant disease. These results provide an insight into the preclinical biology of ovarian neoplasia that may help in designing methods for early detection of this disease, and demonstrate the usefulness of the JANUS serum bank as a resource in evaluating serum tests.

Progress and Challenges in Screening for Early Detection of Ovarian Cancer

“…mucinous and borderline carcinomas) are likely to be associated with lower levels of CA125 than invasive serous cancers (28). In addition, it became apparent that CA125 could be elevated in the preclinical asymptomatic phase of the disease as raised levels were found in 25% of 59 stored serum samples collected 5 years prior to the diagnosis of ovarian cancer (29). In a prospective ovarian cancer screening study of Swedish women, a specificity of 97% and PPV of 4.6% was achieved using CA125 (Ն30 U/ml) in 4,290 volunteers aged 50 years and older (30).…”

Diagnostic Markers of Ovarian Cancer by High-Throughput Antigen Cloning and Detection on Arrays

“…The most extensively investigated biomarker for screening of ovarian cancer is CA-125, whose serum levels are elevated in 50% of stage I and 90% of stage II to IV ovarian cancer patients (1). However, elevated CA-125 levels have also been observed in healthy women during menstruation and in patients with other gynecologic diseases and other malignancies, which results in a high falsepositive rate for CA-125 (2,3).…”

Early detection of ovarian cancer

“…patients who developed ovarian cancer after having previously banked serum specimens in the JANUS serum bank in Norway. 30 In this study median CA 125 levels of the patients who developed ovarian cancer were significantly elevated over controls. Interestingly, the mean time between serum collection and the diagnosis of cancer was 68.2 months.…”

“…CA 125 has been shown to be elevated prior to the clinical development of primary and recurrent ovarian cancer. 30,31 In those patients with early-stage disease, however, CA 125 is elevated in less than half of the cases. 28 Further, in premenopausal patients, several benign conditions are also associated with mild elevations of CA 125.…”