Serial CA 125 Testing May Be the Key to Successful Screening for Ovarian Cancer

April 1, 1996

LONDON--Women who have persistent elevations in the serum marker CA 125 may be at substantially increased risk for ovarian cancer, a large study of women in the United Kingdom has shown.

LONDON--Women who have persistent elevations in the serum markerCA 125 may be at substantially increased risk for ovarian cancer,a large study of women in the United Kingdom has shown.

Ian Jacobs, MD, of St. Bartholomew's Hospital, London, and hiscoinvestigators at Harvard, found that the use of serial CA 125measurements, with the addition of ultrasound when indicated,was an acceptable and highly specific method of screening womenfor ovarian cancer.

The researchers caution that clinical application of the methodwould be premature, with the possible exception of women who areat very high risk, ie, those who have a strong, confirmed familyhistory or who carry a mutation of the BRCA1 gene.

Their study included 22,000 asympto-matic postmenopausal womenover age 45 who underwent baseline CA 125 screening and then wererandomized to be followed with no additional CA 125 screeningor with annual screening for 3 more years.

Women who had elevated CA 125 levels (greater than 30 U/mL) onany screening test also underwent ultrasound and repeat bloodscreening until either the scans suggested an abnormality warrantingsurgical investigation (ovarian volume greater than 8.8 mL) orthe CA 125 level normalized.

During the 8-year study, 717 women had some elevation in CA 125at some time. "Most of these elevations subsequently returnedto normal, and the women are perfectly healthy today," Dr.Jacobs said in an interview with Oncology News International.

A small group had a persistently elevated CA 125 but no abnormalityon ultrasound. "We have never found out why. We are stillfollowing them to see if cancer develops, either ovarian or possiblybreast cancer," he said.

But the focus of the study involved the 48 women who developedprimary invasive epithelial ovarian and fallopian tube cancerswithin 8 years.

In 29 of these women, ovarian cancer was diagnosed within 1 yearof screening, and 22 of these cancers were accompanied by elevatedCA 125 levels. Serial levels were available for 15 of these 22,and all showed a rise with time.

"This is the group whose levels kept going up, whereas withoutcancer the levels returned to normal or stayed flat," Dr.Jacobs said. "The key is that the level is not only elevated,it is rising."

Compared with women with normal CA 125 levels, the odds ratiosfor ovarian cancer diagnosis within 1 year were 96 for levelsover 30 U/mL, 247 for levels over 50 U/mL, 377 for levels over100 U/mL, and 738 for levels over 200 U/mL.

Annual screening for ovarian and fallopian tube cancer carrieda specificity of 99% and a sensitivity of 76% (based on 22 of29 cancer patients having elevated CA 125 levels), said StevenSkates, PhD, assistant professor of medicine and biostatistics,Harvard Medical School.

"While the results do not prove that screening saves lives,they do provide strong justification for performing a large randomizedtrial with ovarian cancer mortality as the outcome," Dr.Skates said in an interview.

He believes that by using this new method of calculating riskbased on changes in the serum marker levels, "we can quicklynarrow patients into the high-risk group. By watching the changesover time, we can ensure that not too many women will needlesslyundergo ultrasound testing."

Dr. Jacobs said that "after 10 years of working on this,we have shown that CA 125 can be an acceptable test from the patient'sstandpoint. It is economically feasible, and has an extremelyhigh specificity and sufficient sensitivity to justify a verylarge, expensive randomized controlled trial to see if it actuallysaves lives."

This trial, involving 120,000 women in the UK, has now been launched.It will also examine the usefulness of adding a second tumor marker,OVX-1, which preliminary data suggest may detect some ovariancancer cases missed by CA 125.

[Editors' note: Dr. Jacobs had been scheduled to present the studyresults at the Society of Gynecologic Oncologists meeting in NewOrleans but was unable to attend because of family illness.]