Evidence of Benefit
CA 125 Levels
CA 125 is a tumor-associated antigen that is used clinically to monitor patients with epithelial ovarian carcinomas.[8,9] The measurement of CA 125 levels, in combination with TVU, is the ovarian screening intervention being evaluated in the PLCO.[5,11] The most commonly reported CA 125 reference value that designates a positive screening test is 35 U/mL, and this was the reference value used in the PLCO to define an abnormal test result. Elevated CA 125 levels are not specific to ovarian cancer and have been observed in patients with nongynecological cancers  and in the presence of other conditions such as the first trimester of pregnancy [12,13] or endometriosis. The sensitivity of the CA 125 test for the detection of ovarian cancer was estimated in two nested case-control studies using serum banks.[15,16] The sensitivity for CA 125 levels of at least 35 U/mL ranged from 20% to 57% for cases occurring within the first 3 years of follow-up; the specificity was 95%. The positive rates across the first four rounds of screening in the PLCO trial were fairly constant, ranging from 1.4% to 1.7% and were lower than the rates for TVU. The PPV was higher for CA 125 than for TVU, ranging from 2.1% to 3.2% in the four rounds of screening.
Another study, the Shizuoka Cohort Study of Ovarian Cancer Screening randomly assigned women to a screening group (n = 41,668) or a control group (n = 40,799) between 1985 and 1999 at 212 hospitals in the Shizuoka prefecture of Japan. The screening protocol comprised ultrasound and CA 125 tests annually. Women with abnormal findings were referred to a gynecological oncologist. Ovarian cancer diagnoses were determined by record linkage to the Shizuoka Cancer Registry in 2002. The annual death certificate file in Shizuoka was checked to ascertain vital status. The mean follow-up time was 9.2 years, and the mean number of screens per woman was 5.4. There were 35 ovarian cancers detected in the screening group and 32 in the control group with a nonsignificant difference in the stage distribution. Nine percent of regular screening attendees had at least one false-positive result.
A CA 125 screening program of 22,000 postmenopausal women with subsequent transabdominal ultrasound for those with elevated CA 125 levels (reference value of 30 U/mL) detected 11 of 19 cases of ovarian cancer occurring in the cohort, for an apparent sensitivity of 58%. The specificity for this screening study was 99.9%. Three of the 11 cases detected through screening were stage I disease. In one prospective screening study, the specificity of CA 125 levels of 35 U/mL was 97.6%. Ten-year follow-up of this cohort of 5,550 women screened from 1987 to 1989 in the Stockholm region of Sweden revealed 29 ovarian cancers versus 24 expected cases. Compared with the cancers diagnosed after the screening period, those detected by CA 125 tests had a higher proportion of early-stage disease and better survival measured from diagnosis. Both end points, however, are subject to bias, and the survival of all ovarian cancers combined did not differ from the age-adjusted ovarian cancer survival in the Stockholm population.