Objectives: To determine whether CA 125 measurement is superior to ultrasound imaging performed by an experienced examiner for discriminating between benign and malignant adnexal lesions, and to determine whether adding CA 125 to ultrasound examination improves diagnostic performance.
Methods: This is a prospective multicenter study (International Ovarian Tumor Analysis (IOTA) study) conducted in nine European ultrasound centers in university hospitals. Of 1149 patients with an adnexal mass examined in the IOTA study, 83 were excluded. Of the remaining 1066 patients, 809 had CA 125 results available and were included. The patients underwent preoperative serum CA 125 measurements and transvaginal ultrasound examination by an experienced ultrasound examiner blinded to CA 125 values. The examiner classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant. The outcome measure was the sensitivity and specificity with regard to malignancy of CA 125, ultrasound imaging and their combined use, the 'gold standard' being the histological diagnosis of the adnexal mass removed surgically within 120 days after the ultrasound examination.
Results: There were 242 (30%) malignancies. For 534 tumors judged to be certainly benign or certainly malignant by the ultrasound examiner the sensitivity and specificity of ultrasound examination and CA 125 (> or =35 U/mL indicating malignancy) were 97% vs. 86% (95% CI of difference, 4.7-17.2) and 99% vs. 79% (95% CI of difference, 15.7-24.2); for 209 tumors judged probably benign or probably malignant, sensitivity and specificity were 81% vs. 57% (95% CI of difference, 12.3-36.0) and 91% vs. 74% (95% CI of difference, 8.5-25.7); for 66 tumors that were difficult to classify, sensitivity and specificity were 57% vs. 39% (95% CI of difference, -9.7 to 41.1) and 74% vs. 67% (95% CI of difference, -14.6 to 27.7). Diagnostic performance deteriorated when CA 125 was used as a second-stage test after ultrasound examination.
Conclusions: Specialist ultrasound examination is superior to CA 125 for preoperative discrimination between benign and malignant adnexal masses, irrespective of the diagnostic confidence of the ultrasound examiner; adding CA 125 to ultrasound does not improve diagnostic performance. Our results indicate that greater investment in education and training in gynecological ultrasound imaging would be of value.