Media coverage of the preliminary results of an ovarian cancer study raised hopes that a reliable screening test is just around the corner. That doesn’t seem to be the case. There is an urgent need for early screening because 70 percent of women have advanced disease that has gone beyond the ovaries when it is diagnosed, resulting in 15,000 deaths a year.
A new study headed by Dr. Karen Lu of M.D. Anderson Cancer Center involved 3,238 women over age 50 with no significant family history of breast or ovarian cancer. Researchers used an old test, the CA-125, in a new way. CA-125 measures levels of a protein that is elevated in ovarian cancer cells. However, by itself, it has a low sensitivity and specificity for ovarian cancer because other non-cancerous conditions can cause it to be elevated, and many ovarian cancers do not trigger an elevated level. This study incorporated a risk of ovarian cancer algorithm, a mathematical formula that calculates a woman’s risk of having ovarian cancer based on age and CA-125 levels over time, and assigns her to risk categories based on what is currently known about ovarian cancer patterns.
Dr. Francisco Xynos, director of the Division of Gynecologic Oncology at Saint Louis University Medical Center, says that by targeting post-menopausal women, researchers found less variability in results. Prior to menopause, CA-125 can be elevated due to uterine fibroids or endometriosis, both of which die off after menopause. “The results in this study are very preliminary, and the test is still not specific,” says Xynos. “What makes the CA-125 more useful is a computer program that compares changes in the CA-125 levels in the same woman over time to profiles seen in ovarian cancers.”
Xynos says that the computer profile ranks women into low, medium and high risk, based on the algorithm and their changes in CA-125 levels. “Out of 3,200 participants, 85 were high risk,” he explains. “Eight had surgery, and in three cancer was found. Of all the women, 90 percent were low risk. To apply a screening protocol to a large population is very expensive, so we want to have evidence that it’s worth it.” He says the study population was not large enough to determine false negative rates for the CA-125. Another study started in the United Kingdom will look at 200,000 women and may yield better answers.
Dr. Teresa Knight, an ob/gyn with Women’s Health Specialists, says that a woman with an ovarian mass on ultrasound and a high CA-125 is less likely to be a false positive; however, the false negative rates with the CA-125 run as high as 50 percent. Knight says the trouble with ovarian cancer is that you can’t just reach in and biopsy the ovary because if it is cancer, that could spread it.
Knight shares three insights about ovarian cancer: The lifetime risk of developing ovarian cancer is 1.4 percent; a family history of premenopausal breast cancer, uterine cancer or ovarian cancer at any age, or colon cancer before age 50 should drive you to your doctor; and if you are in this high risk category for the disease, you should be getting a CA-125 and pelvic ultrasound every six months.
Dr. David Mutch, division chief of gynecologic oncology at Washington University School of Medicine, also calls this new study preliminary and cites a larger study, the Prostate, Lung, Colon and Ovary study (PLCO), in which serial CA-125 screenings and vaginal ultrasound were done on more than 30,000 women with no apparent benefit. Preliminary results of the PLCO did not change current recommendations against screening the general population. “There is hope that by using this new algorithm for risk ranking, combining screening with transvaginal ultrasound, and then further refining it in the larger study in the UK we can increase the predictive value of the testing,” Mutch says.
Mutch says what we need is a totally new test that is cheap and sensitive enough to increase the positive predictive value of this deadly disease.