Description of the Evidence
The UKCTOCS published sensitivity and specificity results from their prevalent screen. The ultrasound screening arm had several levels of screening and possible referral strategies: an abnormal scan resulted in a repeat scan in 6 to 8 weeks, and if still abnormal, a referral was made for clinical assessment. Of 53 total cancers (screen-detected and interval cancers in the following year), 45 were screen positive by ultrasound (two abnormal scans) for a sensitivity of 84.9%. For invasive cancer, the sensitivity was 75%. Specificity of the ultrasound screening arm was calculated to be 98.2%.
CA-125 is a tumor-associated antigen that is used clinically to monitor patients with epithelial ovarian carcinomas.[13,14] Measurement of CA-125 concentrations has been proposed as a potential marker for the early detection of ovarian cancer, either as a single test with a threshold cutpoint or in algorithms examining the change in levels over time. The two randomized trials have included CA-125 either in parallel or sequentially with TVU for multimodality screening. 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 Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial (NCT00002540) to define an abnormal test result. The measurement of CA-125 levels, in parallel combination with TVU, is the ovarian screening intervention evaluated in the PLCO.[16,17] 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 [18,19] 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.[21,22] 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%.
A phase II/III biomarker study was conducted to evaluate the sensitivity of several markers of ovarian cancer, including CA-125 concentrations, using specimens collected from ovarian cancer patients at four sites. The estimated sensitivity for early-stage disease (stage I and II ovarian cancer) was 56% (95% confidence interval [CI], 49%–72%) for a cutpoint set to obtain a fixed specificity of 95%. The threshold for the cutpoint for CA-125 at 95% specificity was 24 U/mL. For all cases (56% of cases had stage III or IV disease at diagnosis), the sensitivity was 73% (95% CI, 64%–84%). When the clinical cutpoint of 35 U/mL was used, the sensitivity decreased.