ELEVATION OF MULTIPLE SERUM MARKERS IN PATIENTS WITH STATE-I OVARIAN-CANCER

Background: The high overall mortality from ovarian cancer (>60%) rela tes, in part, to delays in diagnosis. When ovarian cancer is detected in stage I (International Federation of Gynecology and Obstetrics stag ing), up to 90% of patients can be cured. Transvaginal sonography can detect early-stage disease with great sensitivity, but it is expensive and lacks specificity. Although serum marker assays could provide a l ess expensive and more convenient initial screening test, the sensitiv ity of assays varies. Measurement of serum CA 125 in conjunction with ultrasound screening as a second-line test confers high specificity bu t detects only about one half of early stage ovarian carcinomas. Purpo se: The purpose of this retrospective study was to determine whether a ssays of multiple serum markers would improve sensitivity by detecting a higher percentage of stage I ovarian cancers than the CA 125 assay alone. Methods: Using immunoradiometric assays, we measured preoperati ve serum levels of CA 125 tumor-associated antigen, macrophage colony- stimulating factor (M-CSF), and OVX1 in 46 patients with stage I ovari an cancer of different histologies and 237 patients with benign pelvic masses. We also assayed sera from 204 apparently healthy women who ha d participated in a screening trial and remained free from cancer at 1 year of follow-up. All specimens were obtained from cryopreserved ali quots. Marker levels were considered to be elevated when levels of CA 125 were greater than 30 U/mL, M-CSF levels were greater than 3.1 ng/m L, or OVX1 levels were greater than 12.1 U/mL. Results: At least one o f the serum markers was elevated in 98% of patients with stage I ovari an cancer; CA 125 levels were elevated in 67%. By the same criteria, 1 1% of healthy individuals and 51% of patients with benign pelvic masse s had at least one elevated marker value. Thus, the sensitivity of the combination of assays for the three serum markers was significantly g reater than the sensitivity of the CA 125 assay (P<.0005) and specific ity was moderate. Conclusion: A panel of these three tumor markers can identify early-stage ovarian cancer with extremely high sensitivity a nd moderate specificity. Implications: Elevation of one or more serum markers should be evaluated further as an indication for transvaginal sonography in apparently healthy women. Such a strategy might substant ially reduce the expense and improve the specificity of screening comp ared to the use of ultrasound alone. Prospective studies with a large cohort of patients at high risk for ovarian cancer will be required to confirm these findings.