CA125 is useful for monitoring epithelial ovarian cancer patients during their chemotherapy, but the role of CA125 is still being defined in a screening setting (43–49). Regarding the sensitivity of the test, elevated CA125 levels are seen in 50% of patients with stage I disease (43,48). Data suggest that the specificity of CA125 is improved when the test is combined with transvaginal ultrasonography or when the CA125 levels are followed over time (49,50). These data encouraged the development of prospective screening studies in Sweden and the United Kingdom (45,47). In these studies, patients with elevated CA125 levels (>30 U/mL) underwent abdominal ultrasonography, and 14 ovarian cancers were discovered among 27,000 women screened. About four laparotomies were performed for each case of cancer detected (47).
A randomized trial of nearly 22,000 women aged 45 years or older was performed in the United Kingdom (50). The patients were assigned to either a control group of routine pelvic examination (n = 0,977) or to a screening group (n = 10,958). The screening consisted of three annual screens that involved measurement of serum CA125 levels, pelvic ultrasonography if the CA125 was 30 U/mL or higher, and referral for gynecologic examination if the ovarian volume was 8.8 mL or greater on the ultrasonography. Of the 468 women in the screened group with an elevated CA125, 29 were referred for surgery, 6 cancers were discovered, and 23 had false-positive screening results, yielding a positive predictive value of 20.7%. During a 7-year follow-up period, cancer developed in 10 additional women in the screened group, as it did in 20 women in the control group. Although the median survival of women in whom cancer developed in the screened group was 72.9 months, compared with 41.8 months in the control group (p = .0112), the number of deaths did not differ significantly between the control and screened groups (18/10,977 vs. 9/10,958; relative risk 2.0 [0.78 to 5.13]). These data show that a multimodal approach to ovarian cancer screening is feasible, but a larger trial is necessary to determine whether this approach affects mortality. Such a three-arm randomized trial is ongoing in the United Kingdom, and the anticipated accrual is approximately 50,000 women per study arm and 100,000 women in the control arm. Based on the risk of ovarian cancer (ROC) algorithm for CA125 levels, patients in the third group will be referred for transvaginal ultrasonography and/or surgery (51). Women will be screened for 3 years and studied for 7 years. The aims of this trial are to determine the feasibility of screening for ovarian cancer and whether ovarian cancers can be diagnosed at an earlier stage and the impact of early detection on survival.
Another approach is the use of proteomic patterns to identify ovarian cancer using surface-enhanced laser desorption ionization time-of-ﬂight (SELDI-TOF) technology (52). In a study using this technology, the sensitivity for predicting ovarian cancer was 100%, with a specificity of 95% and a positive predictive value of 94%. The assay correctly identified all 18 women with stage I tumors. This technology is in the early phases of development and validation, and its efficacy has yet to be demonstrated in large population-based studies (53).