Major Finding: The specificity of a new screening approach developed for post-menopausal women at average risk for ovarian cancer was 99.9%.
Data Source: A single arm, prospective, multi-center study of 3,252 women aged 50-74.
Disclosures: One of the study authors, Dr. Herbert A. Fritsche, disclosed that he received research funding from Roche Diagnostics. Another study author, Dr. Robert C. Bast, Jr., disclosed that he serves as a consultant and advisor to Fujiresio Diagnostics, Inc. He also receives other remuneration and royalties for helping to invent the CA-125 assay.
A staged algorithm that incorporates the CA-125 assay to screen postmenopausal women for ovarian cancer has a near-perfect specificity of 99.9%, according to a single arm, multicenter study that enrolled more than 3,200 women at average risk of the disease.
If confirmed in larger studies, this approach could be used to detect ovarian cancer in its early, more curable stages, lead author Dr. Karen Lu said.
“Ovarian cancer is the most lethal gynecologic cancer,” said Dr. Lu, professor of gynecologic oncology at the University of Texas M.D. Anderson Cancer Center, Houston. “Greater than 75% of cases present with advanced stage disease, when cure rates are less than 30%. If caught at an early stage, cure rates are 60%-90%, but at the current time there are no effective screening methods.”
For the 9-year study, scheduled to be presented during ASCO's annual meeting in Chicago, Dr. Lu and her associates enrolled 3,252 women aged 50-74 years with no significant family history of breast or ovarian cancer to be screened with the Risk of Ovarian Cancer Algorithm (ROCA). She described ROCA as a mathematical model that takes into account a woman's age as well as changes in the values of her CA-125 assay over time.
“From here there are three possibilities,” she explained. “Those individuals who have a low ROCA score are told to come back at 1 year for a repeat CA-125. Those who have an intermediate ROCA score are told to come back at 3 months for another CA-125, and those who have a high ROCA score are triaged to a transvaginal ultrasound and referral to a gynecologic oncologist.”
After following the women for 9 years the researchers found that the average annual rate of referral for CA-125 assays every 3 months was 6.8% and that the average annual rate of transvaginal ultrasound and referral to a gynecologic oncologist was only 0.9%. “Each year the overwhelming majority of women were triaged to the low-risk category—an annual CA-125,” Dr. Lu said.
Cumulatively, 85 women (2.6%) received transvaginal ultrasound and subsequent referral to a gynecologic oncologist. Of these, eight required surgery: three for invasive ovarian cancers (two stage 1C and one stage IIB), two for borderline ovarian tumors, and three for benign ovarian tumors. This translated into a positive predictive value of 37.5%. “This means that three operations would be necessary to detect one case of invasive ovarian cancer,” she said.
The combined specificity of ROCA followed by transvaginal ultrasound was 99.9%, “which means that there were very few false positive.”
Dr. Lu emphasized that while results of the ROCA screening strategy are encouraging, “they are not practice changing at this time. We need to await the results of a definitive ovarian cancer screening trial that uses mortality as an end point, and uses the same ROCA algorithm.” That trial of more than 200,000 women is underway in the United Kingdom, she said. Results are expected in 2015.
ASCO President Dr. Douglas W. Blayney said that the ROCA algorithm “represents yet another example of personalized medicine. Here, we have a personalized screening strategy for a vicious type of cancer. This also represents a more refined application of known technology. The CA-125 is widely available, as is transvaginal ultrasound, which is intrusive and technologically somewhat difficult to interpret. Here, we have a staged application.”