HOUSTON – May 20, 2010 (Cancer Digest) – Measuring the change in blood levels of a protein long used as an indicator of ovarian cancer recurrence may be useful for initial detection of the otherwise silent cancer, say researchers. Led by Dr. Karen Lu, professor in the Department of Gynecologic Oncology at M.D. Anderson Cancer Center, the research | M.D Anderson's Dr. Karen Lu, and Dr. Robert Bast |
"Over the last ten years, there's been a lot of excitement over new markers and technologies in ovarian cancer," Lu said in a prepared statement. "I and other scientists in the gynecologic oncology community thought we would ultimately find a better marker than CA-125 for the early detection of the disease. After looking at new markers and testing them head-to-head in strong, scientific studies, we found no marker better than CA125."
In the study 3,252 women were enrolled from seven sites across the country, with MD Anderson serving as the lead site. All were healthy, post-menopausal women, ages 50-74, with no strong family history of breast or ovarian cancer. The study's primary objective was to test how specific, the test was for identifying ovarian cancer without indicating cancer when none was present. The researchers also looked at the positive predictive value, or the number of repeat tests needed to detect a case of ovarian cancer.
Each woman received a baseline CA-125 blood test, which was then evaluated using a statistical model called the Risk of Ovarian Cancer Algorithm (ROCA). The model takes into account the patient's age and CA-125 score. The women were then categorized into one of three risks groups to be followed according how high their risk. Women given a “low-risk” score came back in a year for a follow-up blood test. Those with an "intermediate risk," underwent a repeat CA125 blood test in three months. The "high-risk" group underwent transvaginal sonography (TVS) and were instructed see a gynecologic oncologist.
Based on the change in CA-125 levels over time, an average of 6.8 percent of the women per year were referred to the intermediate risk group and an average of 0.9 percent were referred to the high risk group and received the transvaginal ultrasound and referral to a gynecologic oncologist. Of those women, eight underwent surgery: five were found to have ovarian cancer, three with invasive and two with borderline disease; and three had benign tumors.
That works out to an accuracy for cancer of 37.5 percent with no more than three retests required to detect each case of ovarian cancer. The screening failed to detect two borderline ovarian cancers.
Significantly, said Lu, is that the three invasive ovarian cancers detected were high-grade tumors, the most aggressive form of the disease, and were caught early at stage IC or IIB, when the disease is not only treatable, but most often curable. Lu also noted that all three women found to have invasive disease were monitored at low risk for three years or more prior to a rising CA-125.
Dr. Robert Bast, the MD Anderson researcher who first discovered the link between CA-125 and recurrent cancer explained that this use of the CA-125 in combination with other tests might be accurate enough to detect ovarian cancer in women who have no symptoms of the disease.
"CA-125 is shed by only 80 percent of ovarian cancers," explained Bast. "At present, we are planning a second trial that will evaluate a panel with four blood tests including CA-125 to detect the cancers we may otherwise miss with CA-125 alone. The current strategy is not perfect, but it appears to be a promising first step."
While encouraging, the findings are neither definitive, nor immediately practice-changing, stressed Lu; who also said a large, randomized prospective screening trial still needs to be conducted. Such research is ongoing in the United Kingdom. Results from more than 200,000 women should be known by 2015.
If a larger study shows survival benefit, the simple blood test could offer a much-needed screening tool to detect ovarian cancer in its early stages - even in the most aggressive forms - in post-menopausal women at average risk for the disease.
"As a clinician treating women with this disease for more than 10 years, I've become an admitted skeptic of ovarian cancer screening,” Lu said. “Now, with these findings, I'm cautiously optimistic that in the not too distant future, we may be able to offer a screening method that can detect the disease in its earliest, curable stages and make a difference in the lives of women with this now-devastating disease."
SOURCE: adapted from press materials provided by M.D. Anderson Cancer Center
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