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Preliminary results from a United Kingdom study found that two screening strategies – the CA-125 blood test and a painless transvaginal ultrasound – are effective at finding ovarian cancer early, when it is more easily treated.
Overall, the study found that 48.3 percent of the cancers detected by transvaginal ultrasound alone or with a combination of ultrasound and blood test were at an early stage (Stage I or Stage II). About 90 percent of women with Stage I ovarian cancer at the time of detection are cured with conventional treatment.
Traditionally, however, most women are diagnosed with Stage III or IV ovarian cancer, resulting in a high fatality rate. The five-year survival rate for women diagnosed with Stage III or IV cancer is 27 percent and 16 percent respectively, the researchers reported.
How the study was conducted The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was launched in 2001. The results, reported in the April issue of Lancet Oncology, represent screenings of about 100,000 women through 2005. Researchers will follow up through 2014 before the final results will be reported. Ultimately, the study is designed to answer whether screening for ovarian cancer is effective in saving women’s lives.
The initial results come from 202,638 postmenopausal women ages 50 to 74 (average age of nearly 61) recruited from 27 centers in England, Wales and Northern Ireland. In this randomized, controlled trial, half of the women were not screened; one-fourth had an annual screening with the blood test for CA-125, which checks for tumor markers indicative of ovarian cancer, followed by transvaginal ultrasound if necessary; and one-fourth had an annual screening with transvaginal ultrasound alone.
Women who had screenings with abnormal findings had repeated screenings and were referred for further evaluation and treatment, including surgery, if necessary.
Study findings Researchers reported that either screening method found most of the diagnosed ovarian cancer cases: 34 of 38 cases (90 percent) were found with the combined screenings; 24 of 32 cases (75 percent) with the transvaginal ultrasound alone. Twenty-eight of the 58 cancers (48.3 percent) found were early – Stage I or II.
Repeat testing was needed more often in those women who underwent ultrasound screening alone (12 percent versus 9.1 percent with the combined screening). Also, those in the ultrasound-screening alone group were more apt to have surgery, which researchers said was due to the higher prevalence of benign lesions in postmenopausal women.
Based on these preliminary findings, the study authors said that both transvaginal ultrasound and the CA-125 blood test “remain at the core of all new screening and diagnostic strategies being proposed for ovarian cancer” with both strategies demonstrating “encouraging performance characteristics.”
Study limitations The authors note a limitation of the study was not using a morphological (form and structure) index that may improve the ability of doctors to tell the difference between benign (noncancerous) and cancer tumors on ultrasound scans. They also noted that they did not collect data on cancers in the control group, and a study selection process may have resulted in a high number of healthy participants.
Screening for ovarian cancer The Ovarian Cancer Screening Program is one of the Markey Cancer Center’s clinical research trials aimed at improving the health conditions of women across the Commonwealth.
Postmenopausal women over the age of 50 without symptoms or women over the age of 25 with a documented history of ovarian cancer are eligible to participate. Screening involves transvaginal ultrasound imaging of the ovaries. The test, which takes 5 to 10 minutes, is painless.
Directed by Dr. John R. van Nagell, this program provides free ovarian screenings in Lexington, Elizabethtown, Somerset, Prestonsburg, Maysville and Paducah. For more information, call toll free 1-800-766-8279 or 859-323-4687.
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For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.
This is a good study. It confirms that screening can detect ovarian cancer at an earlier stage than it’s normally detected without screening. It also establishes the fact that the combination of the blood test for ovarian cancer – CA-125 – with ultrasound is probably more effective than ultrasound alone.
“Of women whose ovarian cancer was detected by screening, 82 percent had Stage I or II disease compared to 30 percent of women in the unscreened population.”
But this study doesn’t answer the question of what is the optimal screening algorithm. I don’t think anyone believes that either CA-125 alone or ultrasound alone is as effective as both of them together in finding ovarian cancer early. The question remains, which is better first?
Is it better to do it as we are doing it here at the University of Kentucky, with the transvaginal ultrasound first and then use other methods to increase the positive predictive value of the ultrasound? Or is it better to use CA-125 first? We are trying to develop an ideal algorithm for screening in order to detect ovarian cancer earlier.
We started our ovarian cancer screening study in 1987 and published our first results in 1991. Our findings demonstrate that annual screening with ultrasound improves early detection and saves women’s lives. We are accruing about 10,000 patients a year throughout Kentucky into our study and have now screened 35,000 women for an average of six years. Our study is the largest institutional ovarian screening trial in the United States.
“The ultimate cure rate for a woman with advanced ovarian cancer is only about 10 percent. So clearly, something needs to be done to increase early detection.”
In our study, if the ultrasound is abnormal, we perform a repeat ultrasound in four weeks. If the repeat ultrasound is abnormal, we perform a CA-125 blood test and morphology indexing. Although sonography (another word for ultrasound) can reliably detect even small ovarian tumors, it is not completely accurate in differentiating a benign ovarian tumor from ovarian cancer. We use morphology (form and structure) indexing to identify certain patterns that are associated with benign or noncancerous tumors. If the patient’s CA-125 is normal and the morphology index indicates a benign tumor, she may not need to have surgery and can be followed periodically with repeat ultrasound.
Both our study and the trial from the United Kingdom detected ovarian cancer at a significantly earlier stage than when women did not have screening. The University of Kentucky Ovarian Cancer Screening Program is an ongoing trial; we published results from this trial in 2007 in the journal Cancer. What we showed was that 82 percent of women whose ovarian cancer was detected by screening had Stage I or II disease compared to 30 percent of women in the unscreened population.
Without screening, about 70 percent of women present with Stage III or IV disease. This is important to note because only 30 percent of women with advanced ovarian cancer will be alive in five years after treatment and two-thirds of them will still have disease that cannot be cured. Therefore, the ultimate cure rate for a woman with advanced ovarian cancer is only about 10 percent. So clearly, something needs to be done to increase early detection.
Limitations of the pelvic examWe also have done studies here at the University of Kentucky that show routine pelvic examination is not effective in detecting small ovarian tumors. Therefore, you may have a pelvic examination that is reported as normal, but still have a small undetectable ovarian abnormality. Pelvic examinations just do not reliably pick up early ovarian cancer, particularly in women who are overweight or who have a large uterus.
Signs of ovarian cancer
As a gynecologic oncologist, it is frustrating and tragic to see women presenting with advanced ovarian cancer. Recent research has indicated that ovarian cancer may produce specific symptoms. These symptoms include bloating, early fullness after eating and pelvic pain. If a postmenopausal woman suddenly develops these symptoms, she should contact a physician for further evaluation.
We hope that as a result of the work we and others have done, every woman over the age of 55 will one day be able to get an ultrasound at the time of her annual pelvic examination.
Dr. van Nagell is director of gynecologic oncology at UK Markey Cancer Center and professor of obstetrics and gynecology at the UK College of Medicine.
Each issue of Advances & Insights summarizes an important piece of medical news, accompanied by commentary from a UK expert.
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