Clinical Newswire, June 7, 2010 (Chicago, IL) - A new 2-stage screening approach to detect ovarian cancer in postmenopausal women at an average risk has been tested in the United States with promising results, according to research presented at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO). The approach uses a mathematical model based on trends in CA-125 blood test results and patient age, followed by transvaginal ultrasound and referral to surgery if necessary.
Ovarian cancer is the most lethal gynecologic cancer and the 4th leading cause of death from cancer in women. A major reason for the high mortality is that 75% of cases are diagnosed when the disease is at an advanced stage, when cure rates are less than 30%. If detected at stage I or II, the cure rates are between 60-90%, however currently there are no effective screening methods. Two screening modalities studied in the past, CA-125 protein and transvaginal sonography (TVS), both have their limitations. CA-125 is a tumor marker protein that is elevated in ovarian cancer and can be measured from a blood sample, however it has a limited sensitivity, while TVS is more sensitive but is associated with increased false positive rate and more expenses.
In the current study, led by Karen Lu, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, the researchers evaluated a “Risk of Ovarian Cancer Algorithm” (ROCA). The algorithm is based on a patient’s age and trends in CA-125 blood test results over time.
Women underwent an annual CA-125 test and risk was recalculated with each new CA-125 test. Those with high scores were referred to TVS, and, when needed, to a gynecologic oncologist to determine if surgery was necessary. The ROCA was tailored to each individual woman’s baseline based on her CA-125 values and only a small proportion of women were referred to TVS and clinical evaluation. Those at intermediate risk were scheduled to repeat the CA-125 test after 3 months, and those at low or “normal” risk repeated the test annually.
The study was a prospective, single-arm study conducted over 9 years, starting from 2001, in 7 centers throughout the United States. 3,252 postmenopausal women between 50 and 74 years and no significant family history of breast or ovarian cancer were included. On an average annual basis, less than 1% of the women were classified as “high-risk” and required TVS. Overall, the vast majority (82%) of women were classified as “normal risk” and did not require anything other than coming back for annual CA-125 blood tests, and only 2.6% (n=85) of the women were referred for TVS and physician consultation,. There were 8 surgeries based on the ROCA results, 5 ovarian cancers were identified and all were early stage. Three of the patients had high grade invasive ovarian cancer and two had borderline tumors. Three of the 8 women who had surgery did not have ovarian cancer, and 2 of these 3 women had benign ovarian tumors. None of the women who were diagnosed with ovarian cancer had any symptoms at the time of surgery.
The specificity of this approach was very high at 99.9% (95% CI [99.7%, 99.98%]), and the positive predictive value was 37.5 (95% CI [11.1%, 100%]), with no more than 3 surgeries needed to detect 1 case of invasive ovarian cancer.
“The 2-stage strategy for ovarian cancer screening is feasible in the US population of postmenopausal women”, Dr. Lu concludes. Future directions of research include examining a 4 marker panel which includes CA-125, which aims to maintain specificity and increase sensitivity
A large-scale study of ROCA with 200,000 women randomized and 50,000 undergoing the 2 step screening algorithm is under way in the United Kingdom. The results are expected in 2015. If this definitive trial examining mortality as an endpoint validates the algorithm, CA-125 testing may be recommended as part of a woman’s annual health check-up. According to Dr. Lu, “This approach could be a useful and relatively inexpensive tool for detecting ovarian cancer in its early, more curable stages, including the types of ovarian cancer that biologically are the most aggressive”.
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