CA-125 change over time shows promise as screening tool for early detection of ovarian cancer

Evaluating its change over time, CA-125, the protein long-recognized for predicting ovarian cancer recurrence, now shows promise as a screening tool for early-stage disease, according to researchers at The University of Texas MD Anderson Cancer Center.

The findings were presented today by Karen Lu, M.D., professor in MD Anderson's Department of Gynecologic Oncology, in advance of the American Society of Clinical Oncology (ASCO) annual meeting. If a larger study shows survival benefit, the simple blood test could offer a much-needed to detect in it early stages - even in the most aggressive forms - in post-menopausal women at average risk for the disease.

MD Anderson has a long history in the research of the important biomarker. In the 1980s, Robert Bast, M.D., vice president for translational research at MD Anderson and co-investigator on the ASCO study, discovered CA-125 and its predictive value of ovarian cancer recurrence. Since then, researchers at MD Anderson and beyond have been trying to determine its role in early disease detection. The marker, however, can become elevated for reasons other than ovarian cancer, leading to false positives in early screening.

Listen to Dr. Lu and Dr. Bast speak about a possible screening tool for the early detection of ovarian cancer. Credit: MD Anderson

"Over the last ten years, there's been a lot of excitement over new markers and technologies in ovarian cancer," said Lu, the trial's principal investigator. "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."

According to the American Cancer Society, 21,550 women were diagnosed with ovarian cancer in 2009 and another 14,600 died from the disease. The challenge, explained Lu, is that more than 70 percent of women with ovarian cancer are diagnosed with advanced disease.

"Finding a screening mechanism would be the Holy Grail in the fight against ovarian cancer, because when caught early it is not just treatable, but curable," said Lu.

For the prospective, single-arm 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 endpoint was specificity, or few false positives. In addition, the study looked at the positive predictive value, or the number of operations required to detect a case of ovarian cancer.

Each woman received a baseline CA-125 blood-test. Using the Risk of Ovarian Cancer Algorithm (ROCA), a mathematical model based on the patient's age and CA-125 score, women were stratified to one of three risks groups, with the respective follow-up: "low," came back in a year for a follow-up blood test; "intermediate," further monitoring with repeat CA125 blood test in three months; and "high," referred to receive transvaginal sonography (TVS) and to see a gynecologic oncologist.

Based on the women's CA-125 change over time, the average annual rate of referral to the intermediate and high groups were 6.8 percent and .9 percent, respectively. Cumulatively, 85 women (2.6 percent) were determined to be high risk, and thereby received the TVS and were referred 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 - a positive predictive value of 37.5 percent. Consequently, no more than three operations would be required to detect each case of ovarian cancer, explained Lu. The screening failed to detect two borderline ovarian cancers.

Of great importance, said Lu, is that the three invasive ovarian cancers detected were high-grade epithelial tumors, the most aggressive form of the disease, and were caught early (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.

"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.

"As a clinician treating women with this disease for more than ten years, I've become an admitted skeptic of ovarian cancer screening. 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 with this now-devastating disease."

The study is continuing; and, as follow-up, Lu and her team plan to look at combining other markers with CA-125 to determine the screening impact of their combined change over time.

Citation: CA-125 change over time shows promise as screening tool for early detection of ovarian cancer (2010, May 20) retrieved 28 March 2024 from https://medicalxpress.com/news/2010-05-ca-screening-tool-early-ovarian.html
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