Carbohydrate antigen 125 (CA125) testing, already used to predict ovarian cancer recurrence, has now shown strong results as a screening technique for early-stage disease when combined with transvaginal ultrasound.

Despite its predictive value for recurrence of ovarian cancer, CA125 can become elevated for reasons other than ovarian cancer, leading to false positives in early screening. The two-stage screening strategy described by Karen H. Lu, MD, and colleagues in Cancer incorporates changes in CA125 levels over time and age to estimate risk for ovarian cancer.

Lu, who is the chair of the Department of Gynecologic Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, and her team conducted a single-arm prospective study of 4,051 postmenopausal who submitted to annual CA125 testing over the course of 11 years. Women were then triaged to one of three groups according to their scores on the Risk of Ovarian Cancer Algorithm, a mathematical model based on patient age and CA125 value:

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  • next annual CA125 blood test (low risk)
  • repeat CA125 test in 3 months (intermediate risk)
  • transvaginal ultrasound and referral to a gynecologic oncologist (high risk).

The average annual rate of referral was 5.8% for CA125 test in 3 months, and 0.9% for transvaginal ultrasound/specialist review. Of the 10 women who underwent surgery on the basis of ultrasound, four had invasive ovarian cancers. All four of these cancers were high-grade epithelial tumors, the most aggressive form of the disease, and were caught early, at stage IC or IIB. All four women with invasive ovarian cancer had low-risk annual CA125 test values for at least 3 years before those values rose.

Two additional women had ovarian tumors of low malignant potential, one had stage I endometrial cancer, and three had benign ovarian tumors. The screening failed to detect two borderline ovarian cancers.

The findings reflected a positive predictive value of 40% for detecting invasive ovarian cancer, which greatly surpassed the clinical benchmark of 10%, noted the study authors. Specificity was 99.9%.

“I and other scientists in the gynecologic oncology community thought we would ultimately find a better marker than CA125 for the early detection of [ovarian cancer],” commented Lu in a statement from MD Anderson. “After looking at new markers and testing them head-to-head in strong, scientific studies, we found no marker better than CA125.”

Lu emphasized, however, that the findings are neither definitive nor immediately practice-changing. She and her fellow researchers are planning a second trial to evaluate a panel of four blood tests, including CA125, in the detection of cancers that may be missed using CA125 alone.