Researchers are moving closer to developing two new screening tests for ovarian cancer that are expected to help improve the early detection of this leading killer of women.

One approach uses a blood test to monitor levels of a protein known as CA 125 and seems particularly promising in detecting ovarian cancer in postmenopausal women. The other, a modification of ultrasound, may play a role as a nonsurgical method of diagnosing malignant tumors of the ovaries.

"We feel very excited and encouraged about these methods," said Kenneth C. Chu, program director of the Early Detection Branch of the National Cancer Institute's Division of Cancer Prevention and Control. "I think that between the two we are going to find something that is hopefully going to be useful for the early detection of ovarian cancer."

Each year, 20,000 American women -- 80 percent of whom are over 50 -- are diagnosed with ovarian cancer and 12,000 die of the disease. Because ovarian cancer is difficult to detect and mimics other illnesses, 70 percent of women do not know they have the disease until it reaches an advanced stage. Once the illness has spread from the ovaries to the abdomen, the prognosis is poor.

"Only 25 percent of women with advanced ovarian cancer can be cured using existing treatment," said Robert C. Young, president of the Fox Chase Cancer Center in Philadelphia and chairman of a recent NCI workshop on early detection of ovarian cancer. Cancer patients are considered cured if they survive five years after diagnosis without a recurrence.

For decades, scientists have searched for a simple blood test that could alert them to the disease before symptoms occur. So far, the most promising test is the one that measures CA 125, a protein antigen produced by the tumor. First discovered 10 years ago by Robert Bast and Robert Knapp of the Dana Farber Cancer Institute in Boston, CA 125 is currently used as a biological marker to monitor women who already have been treated for ovarian cancer. When levels rise, the odds are good that cancer is returning.

At the same time, the CA 125 test is not seen as a general screening measure for all women, because blood levels of CA 125 can rise for reasons other than ovarian cancer among premenopausal women. Other reasons include pelvic inflammatory disease, pregnancy, abcesses of the fallopian tubes, inflammation of the uterine lining, also known as endometriosis and malignant tumors other than ovarian cancer.

But there is new evidence that CA 125 may be a useful screening tool in women 50 and older. According to two Swedish studies of more than 6,000 women, a high level of CA 125 seems to be a reliable indicator of ovarian cancer before symptoms appear in post-menopausal women.

Led by Vincent Zurawski, a researcher at Centocor (the Pennsylvania-based company now licensed to produce a CA 125 test), a team of Swedish and American researchers screened 1,082 women 40 and older for CA 125 levels. Their findings, published in the March issue of Gynecologic Oncology found that CA 125 levels rose above 65 units per milliliter in only 1 percent of the population. Normal levels of CA 125 are 35 units per milliliter or below. Women whose levels were elevated tended to have some kind of ovarian problem, showing that the test could be useful in helping to pinpoint early ovarian cancer.

In the second phase of the study, which was presented last week here at the annual meeting of the American Association for Cancer Research, the team screened 5,550 women, 40 and older, and monitored their levels of CA 125 for nearly three years.

The findings suggest that there are two conditions where elevated levels of CA 125 can point to ovarian cancer in women 50 and older. The first is when levels are 95 or above. The second is when CA 125 levels of about 30 double within a period of several months to a year and remain at that level.

Other studies show that CA 125 can be a useful diagnostic tool in older women with enlarged ovaries. If CA 125 levels are above 35, these women have an 80 to 90 percent chance of ovarian cancer, Zurawski said. If levels are above 95, "the probablity of ovarian cancer is in excess of 95 percent," he said.

Contrary to a suggestion by Connie Chung during a recent television interview with actor Gene Wilder about his wife, comedian Gilda Radner, who died of ovarian cancer last year, specialists say that women should not routinely ask their physicians for a CA 125 test. It is premature to do that, they say. "I would be very concerned about making suggestions that women go out and {take this test} on a routine basis," Zurawski said. "All the data are not in yet."

Another improvement in early detection of ovarian cancer involves the use of ultrasound -- a procedure that utilizes sound waves to draw images of the ovaries. Two separate reports by British researchers and by a team from the University of Kentucky Medical Center show that ultrasound can be effective in detecting ovarian abnormalities.

Traditional ultrasound measures structural changes but is not a good way of distinguishing malignant from benign ovarian tumors. A modification that allows doctors to take images from the vagina instead of through the abdomen is helping to improve the accuracy of ultrasound. In a study of 1,600 women in Kentucky, Robert Higgins, assistant professor of gynecologic oncology at the University of Kentucky Medical Center in Lexington found 28 suspicious tumors. "Three of those women had ovarian cancer," Higgins said. Two cases involved very small tumors that were not detectable by pelvic exam. Another eight women had a possible premalignant condition. The remaining 17 women had benign tumors.

Another modification of ultrasound may turn the technique into an effective screening test for ovarian cancer. Called Doppler ultrasound, this approach adds a new dimension to the standard ultrasound image by showing pictures of blood flow. The result is a colorful picture that Tom Bourne and his colleagues at the King's College School of Medicine and Dentistry in London, report can detect the difference between cancer and a benign cyst because malignant tumors have more extensive blood flow.

"We don't know how the Doppler ultrasound will pan out," said the University of Kentucky's Higgins. While ultrasound may hold promise as a diagnostic tool, Higgins notes that "it is still experimental."

Meanwhile, cancer specialists are re-evaluating some treatments for ovarian cancer. In March, Fox Chase's Young and his colleagues reported in the New England Journal of Medicine that tumors confined to the ovary can be treated just as effectively with surgery alone as with a combination of surgery and chemotherapy -- thus sparing patients the risks and side effects of powerful anti-cancer drugs.

In this study, half of the 81 women underwent surgery only. The other half underwent surgery and then were treated with melphalan, a powerful drug that fights ovarian cancer but can also cause leukemia, the malignant blood disorder. Five years after treatment, 94 percent of the women who underwent surgery alone and 98 percent of those who had the combination treatment were still alive -- not a statistically significant difference, the researchers reported.

"This paints a more promising picture of ovarian cancer," Young said. Women with the earliest stage of the disease -- about 30 percent of all cases -- who undergo surgery that carefully measures the extent of their disease can survive as well as those who have surgery and chemotherapy, which poses its own risks, he said.

Over all, researchers say they are more optimistic about battling ovarian cancer. As Jonathan S. Berek of the UCLA School of Medicine noted in an editorial accompanying the report, "the five-year survival rate was excellent" -- more than 90 percent -- for tumors that were confined to the ovaries at the time of diagnosis. Found early, said Young, "we have a pretty good idea of how we can cure ovarian cancer."