Ovarian Cancer Screen
Not a screening test but still useful.
Points of Interest : 2005 – CA- 125 OVARIAN CANCER SCREEN
Tests that may be useful for screening in certain circumstances include measurement of the CA 125 tumor marker, ultrasonography, and combinations of the two.
CA 125 tumor marker — Measurement of the serum concentration of the glycoprotein CA 125 antigen is the most widely studied biochemical method of screening for ovarian cancer. Serum CA 125 values are elevated in over 80 percent of women with ovarian cancer. The average reported sensitivities for early stage disease are 50 percent for stage I and 90 percent for stage II [31].
However, the specificity of CA 125 is limited. CA 125 is also increased in patients with other malignancies, including endometrial, breast, lung, and pancreatic cancer [32], as well as in a variety of benign conditions, such as endometriosis [33], uterine leiomyoma, cirrhosis with or without ascites [34,35], and pelvic inflammatory disease. The presence of pleural or peritoneal fluid or disease involvement, whatever the cause, also increases CA 125 levels [36]. Furthermore, CA 125 levels are elevated in approximately 1 percent of healthy women (show table 4) [37], and they fluctuate during the menstrual cycle.
A prospective study of asymptomatic postmenopausal women found that an elevated CA 125 concentration was a powerful predictor of subsequent ovarian cancer risk [38]. In this study, the relative risk of developing ovarian cancer within one year and five years was increased 35.9- and 14.3-fold, respectively with a serum CA 125 concentration 30 U/mL.
Despite these impressive numbers, screening studies using single measurements of CA 125 have not achieved favorable results. Studies of CA 125 in screening for ovarian cancer have focused upon postmenopausal women, since menstrual cycle variations and the prevalence of benign gynecologic conditions in premenopausal women would result in a substantially higher likelihood of false-positive tests. Estimates of the sensitivity and specificity of the CA 125 assay are drawn from three large screening studies in Sweden and England [39-41] and from numerous studies of the test’s performance in women with clinically diagnosed ovarian cancer [31,42]:
The sensitivity of the CA 125 assay (reference level 35 U/mL) for detecting preclinical disease ranges from 70 to 80 percent.
The specificity of a single CA 125 level in community screening studies of postmenopausal women is 98.6 to 99.4 percent. Nevertheless, in an average-risk population with a low prevalence of disease, the false-positive rate remains unacceptably high. In one study it was estimated that there would be 30 false-positive tests for every ovarian cancer detected [31].
The positive predictive value of annual CA 125 testing alone (3 percent) does not meet the level required for screening postmenopausal women at average risk.
The rate of change in CA 125 levels over time appears to be a more specific screening method. In one study, the specificity reached 99.9 percent after redefining a positive test as a CA 125 concentration greater than 35 U/mL that doubles within six months [39]. Other reports have found that the temporal pattern of CA 125 values or the use of tumor markers complementary to CA 125 (eg, OVX1) can increase the specificity to 99.7 percent, with no loss of sensitivity [43]. A large prospective study in 9233 postmenopausal women with two or more measurements of CA 125 that used a modeling method to calculate risk found that compared with a specific cutoff value of CA 125, the model improved sensitivity for detection of ovarian cancer from 62 to 86 percent when specificity was fixed at 98 percent [44].
Thus, a single measurement of CA 125 is not an adequate screening tool for ovarian cancer. A method based upon temporal changes in CA 125 levels could theoretically have sufficient specificity for screening average-risk women. However, no randomized trials exist to demonstrate reduced mortality with use of these methods.