May 20, 2010 -- A new screening approach shows promise for the detection of ovarian cancer in postmenopausal women at average risk of the disease, early testing suggests.
In a study of more than 3,200 postmenopausal women, the approach proved feasible, with "very, very few false-positive results," says study researcher Karen Lu, MD, professor of gynecologic oncology at The University of Texas M.D. Anderson Cancer Center in Houston.
Still, many other approaches that looked promising in early tests have turned out to be false starts, she tells WebMD.
The findings were presented at a news briefing held in advance of the annual meeting of the American Society of Clinical Oncology (ASCO).
Search for a Screening Test
About one in 2,500 postmenopausal women develops ovarian cancer, which is the most deadly gynecologic cancer, Lu says.
The reason: More than 75% of cases are diagnosed at an advanced stage, when cure rates are less than 30%.
"If caught at an early stage, cure rates are 60% to 90%," she says.
As a result, the search is on for an early, reliable screening test for early-stage disease. Years ago, researchers discovered that blood levels of the CA-125 (cancer antigen-125) protein are elevated in women with ovarian cancer. But by itself, CA-125 did not prove useful as an early marker, Lu says.
"While 80% of advanced ovarian cancers have elevated CA-125 levels, only half of early-stage cancers have elevated CA-125 levels," she says.
Plus, CA-125 levels are elevated in women with other cancers, benign ovarian tumors, and pelvic infections, Lu says.
The blood test for CA-125 is currently used to check to see if treatment is working or if cancer has returned.
Recently, researchers started looking at the change in CA-125 levels over time rather than at CA-125 as a single value, Lu says.
"We and others theorized that if someone has low levels and they double, it could be a sign that something is happening even if levels are still low. Alternately, if a woman has a high value and it stays there, [we theorized] it's not likely to be ovarian cancer," she says.
For the new study, the researchers evaluated the "Risk of Ovarian Cancer Algorithm" (ROCA), based on a patient's age and changes in CA-125 blood levels results over time.
Women with the greatest change in CA-125 levels are referred for transvaginal sonography (TVS), and, when needed, to a gynecologic oncologist to determine if surgery is necessary.
The study included 3,238 postmenopausal women aged 50 to 74 without a family history of breast or ovarian cancer. They were followed for up to nine years.
On an annual basis, less than 1% of the women were categorized as high risk of ovarian cancer based on their change in CA-125 levels and referred for TVS.
About 7% of women were categorized as being at intermediate risk -- "their CA-125 levels went up slightly," Lu says -- and told to come back for CA-125 screening every three months.
"So over 90% of women were low risk and just had to come back for CA-125 screening annually," she says.
Of the 85 women categorized as high risk over the course of the study, eight went on to have surgery.
Three of the eight had early-stage aggressive ovarian cancers, "the kind that I as a doctor want to pick up early," Lu says.
"All three women with invasive ovarian cancers had at least three years of low-risk annual CA-125 values prior to a rising CA-125," she adds.
Two women had borderline ovarian tumors, two had benign ovarian tumors, and one had endometrial cancer.
A total of 99.9% of women categorized as being high risk based on the ROCA results did in fact have cancer, meaning that the rate of false-positives "is very, very low," Lu says.
The study also showed that based on ROCA results, no more than three operations were needed to detect one case of invasive ovarian cancer.
"Within the medical community, we feel like it should be no more than 10 operations to detect one case of invasive cancer, so this is within those parameters," Lu says.
There were not enough patients to determine the false-negative rate, Lu says.
The approach missed two borderline cases; however, no invasive ovarian cancers were missed.
"Could these borderline cases become invasive later? It's possible, but biologically, they tend to act differently," Lu says.
Both Lu and ASCO president-elect George W. Sledge Jr., MD, of the Indiana University School of Medicine, say they are cautiously optimistic.
"These early results suggest that looking at an old friend in a new way may be the answer. But I'm skeptical given the false starts," Lu says.
At one cancer meeting last year, "about five groups submitted their best candidates" and none panned out, she says.
Until researchers can show the approach actually saves lives, it will not be ready for prime time, says Sledge, who was not involved with the study.
That is currently being tested in a study of more than 200,000 women in the U.K. Results should be available in four or five years, Lu says.