Serum CA 125 levels in a group of nonhospitalized women: relevance for the early detection of ovarian cancer.

Serum samples were collected from 915 nonhospitalized Roman Catholic nuns with a median age of 55 years (range 19-94 years). Using an immunoradiometric assay, serum CA 125 levels ranged from 0-574 U/mL with a median of 10.5 and mean of 14.3 U/mL. Thirty-six women (3.9%) had serum levels greater than 35 U/mL, and only seven (0.76%) had serum CA 125 levels above 65 U/mL. In only 14 (2.4%) of 586 women aged 50 or older were CA 125 levels above 35 U/mL, and in only three (0.51%) of this group did levels exceed 65 U/mL. Among the seven women with levels above 65 U/ML, five were found to have benign or malignant neoplasms or other masses at the time of entry into the study or during the follow-up interval (mean 311 +/- 103 days). Moreover, in six of seven members of this "false positive" group, some disorder was diagnosed during the study period that might have elevated the CA 125 level. No correlation was found between serum CA 125 levels and a variety of nonmalignant disorders or a variety of concurrent medications. The apparent specificity of the CA 125 assay in this study population suggests that, if used in conjunction with other tests to discriminate ovarian carcinoma from disorders that could elevate serum CA 125 levels, this assay might be a potential component of a strategy aimed at the early detection of ovarian cancer.

Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer.

To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Follow-up CA 125 levels were obtained for those women with initially elevated levels and a group of age-matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels (P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical follow-up with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy.