NIH Consensus Panel's Recommendations for Ovarian Cancer Screening Revisited for Ob/Gyns

SAN FRANCISCO--Enhanced concern by the medical community and bywomen themselves prompted the National Institutes of Health'sOffice of Medical Applications of Research to convene last year'sconsensus conference on ovarian cancer, Vicki Seltzer, MD, saidat the annual meeting of the American College of Obstetriciansand Gynecologists (ACOG).

"Ovarian cancer is the fourth leading cause of cancer deathamong women, with an estimated toll of 13,600 deaths in 1994,"Dr. Seltzer said. Because the disease is often diagnosed late,the death rate is high, as compared with other cancers, and thishas led to considerable public interest in the disease.

"I also believe that the death of Gilda Radner, who didn'tknow she was at high risk for the disease and whose cancer wasdiagnosed late, increased women's concern about ovarian cancer,"said Dr. Seltzer, professor and chair of the Department of Obstetricsand Gynecology, Long Island Jewish Medical Center, New Hyde Park,NY.

The consensus development conference was sponsored jointly bythe National Cancer Institute and the Office of Medical Applicationsof Research, and these organizations outlined the issues to bedebated and selected the members of the planning committee.

The committee, chaired by Dr. Seltzer, then decided which questionsto pose and which experts to invite to give presentations. After2 days of presentations and open discussion, the committee adjournedto draft a statement.

Screening Controversies

In the weeks following Gilda Radner's death, Dr. Seltzer recalledthe concerns of female patients who visited her office. "Womenwere coming in with elevated CA 125 values, wondering where togo from there."

Physicians know from their own practices, Dr. Seltzer said, thatwomen with ovarian cancer are being diagnosed at a late stageof the disease. Physicians need to pay more attention to vaguegastro-intestinal discomforts and pelvic pressure and pain, Dr.Seltzer said, because occasionally these symptoms can be signsof an early ovarian cancer.

Currently, four screening tests are available for ovarian cancer:a rectovaginal pelvic exam, CA 125, pelvic and endo-vaginal ultrasound,and color Doppler--a procedure that should still be consideredinvestigational, she said.

CA 125, although problematic as an independent screening tool,is positive in 80% of patients with epithelial ovarian cancer."However, only half of the patients with stage I have elevatedlevels. What's more, levels of CA 125 are elevated in patientswith endometriosis, liver disease, and pelvic infections. Formany patients with elevated CA 125, we never find out the realcause," Dr. Seltzer said.

For these reasons, the committee decided that CA 125 by itselfis not an adequate screening test.

Some physicians consider transvaginal sonography the screeningmethod of choice. "But we felt that the specificity of sonographymakes it inadequate for use as a single screening modality,"she said.

High-Risk Patients

The committee looked at whether women at higher risk--those whoshould benefit most from screening--could be identified. Riskfactors for ovarian cancer include advancing age, nulliparity,being North American with more than one European ancestor, a personalhistory of endometrial, colon, or breast cancer, or a family historyof these diseases.

"Now there is also concern that taking fertility drugs maybe related to an increased risk," Dr. Seltzer said.

Factors that may reduce a woman's risk of developing ovarian cancerinclude long-term use of oral contraception (ie, greater than5 years), more than one full-term pregnancy, breast-feeding, andtubal ligation.

Dr. Seltzer said that a woman has a one in 70 (1.4%) chance ofdeveloping ovarian cancer if she has no risk factors. If she hasone first-degree relative, her risk climbs to 5%; two first-degreerelatives, 7%; and if she inherits an autosomal dominant gene,80%.

There are three hereditary ovarian cancer syndromes: breast-ovariancancer syndrome; site-specific ovarian cancer syndrome; and Lynchsyndrome II, which includes early onset of polyposis colorec-talcancer, endometrial cancer, upper GI cancer (including biliaryducts, pancreas, and possibly the small intestine), uro-thelialcarcinomas, and ovarian cancer.

In considering all available data, the committee determined thatabnormal screening tests can result in morbidity--and even mortality--whenthey lead to unnecessary surgeries. Although there are good reasonsfor trying to detect ovarian cancer early, the potential risksof screening for some populations of women may outweigh the potentialbenefits, she said.

The committee recommended that all women have a comprehensivefamily history taken by a physician knowledgeable in the risksassociated with ovarian cancer, along with an annual rectovaginalpelvic exam as part of their routine medical care.

While there is no evidence at present to support the routine screening(with CA 125 or ultrasound) of women without a family historyor other high-risk factors, "participation in clinical screeningtrials is an option," she said.

For women with one first-degree ovarian cancer relative, the benefitsof routine screening are also currently unproven, Dr. Seltzersaid. In these cases, if a woman wants to be screened--after herphysician has explained that there's no guarantee that such testingwill be helpful to her (and there are no clinical trials availablein her area), it is not unreasonable for the woman to be screened.

Similarly, there are no conclusive data that screening benefitswomen with two or more relatives who have had the disease, shenoted. However, women in this category are more likely to havehereditary ovarian cancer syndrome than women without such a familyhistory. These women need to be counseled by a gynecologic oncologistor other qualified specialist to evaluate their risk.

Hereditary Cancer Syndrome

Even for women from families with hereditary cancer syndrome,with a lifetime ovarian cancer risk of 40%, there are as yet nodata to show that screening reduces mortality from ovarian cancer,she said. In these cases, however, the risk is so high that thecommittee recommended annual rectovaginal exams, CA 125 determinations,and transvaginal ultra-sonography, to be continued until the womanreaches age 35 or finishes child-bearing, whichever comes first.

"At that point, we recommend prophylactic bilateral oophorectomy,"Dr. Seltzer said, adding that for women in this high-risk category,even a bilateral oophorectomy does not eliminate the risk of peritonealcarcinomatosis.