CA-125 and Ovarian Cancer

During the fall and winter of her early 50s, Ms. “S” began noticing a feeling of pressure in her lower abdomen during sexual intercourse. She ascribed her sensations to ovarian sag because she had a hysterectomy 15 years earlier. From January to May, she dieted and exercised, but she couldn’t seem to lose her puffy belly or decrease her thickened waist. She visited her doctor, who ran blood tests and performed an upper GI series — all normal. Further tests revealed ascites (fluid build up in the abdomen). Finally, an ultrasound revealed a mass. She was referred to a gynecologic oncologist who drained three liters of fluid, relieving her discomfort. She continued these draws, called paracentesis, once a week until her surgical date of August 4th. Her ovarian cancer (OVCA) was definitively diagnosed during that surgery, a full three months after her initial search for an answer. The oncologist seemed surprised that a CA 125 test had never been ordered. Why?

Ms. “C’s” ovarian cancer was caught early, perhaps because she had lost her mother and aunt to the disease, a risk factor which raises a red flag. She had surgery, chemotherapy and radiation, and the doctors pronounced her “cured.” Of course, she was elated to hear the news but troubled by continued elevated CA 125. For those already diagnosed, the CA 125 marker is commonly used to monitor disease activity in response to treatment. If the treatment is working, the level should decrease. The doctors performed laparoscopies to explore but found no disease and repeatedly assured her the CA 125 was wrong. It wasn’t, and she died five years after her original diagnosis at the age of 48 despite being diagnosed early in the disease process.

Perhaps the most well publicized fight against ovarian cancer was that of Gilda, a struggle she recounts in exquisite detail in her wonderful book, “It’s Always Something.” After her treatment had ended and she was assured she was ‘clean,’ she describes a horrifying moment when she learns there was a computer error, and her CA 125 level is not normal after all, but has increased tenfold, indicating the cancer had returned.

CA 125 is a substance (glycoprotein) shed by cancer cells and other inflamed normal cells which eventually ends up in the bloodstream. It is measured by a simple blood assay, which determines the amount of this particular antigen in the blood serum. Depending on which type of test used, “normal” is less than 30-35 U/ml. It costs approximately $125 and is covered by most insurance plans. It is estimated that approximately 80 percent of women with ovarian cancer will have an elevated CA 125 at the time of diagnosis (Note: About 20 percent of women with ovarian cancer do not EVER have an elevated CA 125). Unfortunately, there are many other conditions which may cause the CA 125 level to rise, including benign conditions like endometriosis, PID (pelvic inflammatory disease), uterine fibroids, pregnancy and cirrhosis of the liver. Malignant tumors of the liver, lung, breast, colon, pancreas, endometrium and cervix can also cause an elevation.

Ms. “S” was found to be in Stage IV, the most advanced stage, which meant the cancer had spread outside the ovary. Estimates are that 75 percent of women have either Stage III or Stage IV disease at the time of diagnosis. Ovarian cancer has the highest mortality rate of all gynecological cancers. While the prognosis for those diagnosed with local disease (Stage I or II) is 80 to 90 percent, the overall five-year survival rate is less than 40 percent because diagnosis is delayed in the majority of cases. The lifetime risk of developing ovarian cancer is one in 70 or 1.4 percent. This risk triples for women with one affected first degree relative. If two or more relatives are affected, the risk reaches as high as 40 percent. The literature shows that the risk of developing ovarian cancer for women with mutations of the BRCA 1 gene falls somewhere between 44 percent and 60 percent. BRCA 1 and BRCA 2 have been identified as the two primary genes responsible for an inherited predisposition to breast and ovarian cancer.

Early ovarian cancer usually produces no symptoms and even advanced disease may cause only non-specific symptoms, such as vague abdominal pain, abdominal swelling, indigestion, frequent urination, constipation or diarrhea, and weight change. Pelvic discomfort, low back pain and abnormal vaginal bleeding are also possible symptoms.

If this cancer is so deadly, and there may not be any symptoms until an advanced stage, why aren’t women getting CA 125 tests as a screening precaution? The National Institute of Health (NIH) stated in l995 that there is no evidence yet that CA 125 can be effectively used for widespread screening to reduce mortality. They believe that widespread screening will lead to unnecessary surgery for many women in order to diagnose just a few cases of ovarian cancer (the only way to truly diagnose ovarian cancer is with a biopsy). However, there are a number of studies done over the last few years that indicate that the CA 125 test, when used in conjunction with a pelvic exam and transvaginal ultrasound, is a very effective screening tool. When all three of these tests are negative, it is an extremely high indicator that the woman does not have ovarian cancer.

An argument against the use of the CA 125 as a screening tool is that many other conditions may be causing the elevation. However, whether the underlying condition is benign or malignant, with the exception of pregnancy, all these conditions are abnormal, and there is certainly no disadvantage for a woman to learn she has endometriosis or one of the other disorders. In fact, catching any of those conditions early could prevent serious complications. Women who have had hysterectomies should remember that removing the ovaries is not automatically included in this procedure. Removal of an ovary is called an oophorectomy. For women who have had their ovaries removed, there is still a slight chance of developing ovarian cancer on the peritoneum, the membrane lining the abdominal cavity.

Dr. suggests women get their results in writing along with the name of the test manufacturer, the method (assay type) used and the normal range for that test. This way, should she be required to have future tests, she would know she was comparing results that were taken under the exact same circumstances. He also reminds women that the level varies daily and, on occasion, she might have an extremely high reading. What she should look for is a trend over time, such as doubling outside the normal range. In addition, it is possible to have a temporary increase before a decrease if the tumor is breaking up in response to chemotherapy. False positives are more common in premenopausal women.

So, what can you do?

Know your family history. Have you or any women on either side of your family had ovarian, breast, colon, pancreatic or endometrial (uterine lining) cancer? At present, this is the greatest known risk factor. Some women who have had one or more relatives develop ovarian cancer have preventively had their ovaries surgically removed, taking hormone replacement therapy if they were premenopausal at the time. This is a major surgical procedure and should be discussed thoroughly with your physician and a specialist, such as a gynecologic oncologist

Present theory holds that the fewer cycles the ovary experiences, the lower the risk. That would mean that women with one or more full-term pregnancies, those who breastfed, or those who take oral contraceptives have a lower risk. The question of long-term use of fertility drugs as an increased risk factor is still under investigation.

Having a tubal ligation or hysterectomy decreases risk, but the exact reason is unknown.

Risk starts to increase at age 40. The most common age for diagnosis is 61 to 63. Despite the fact that ovarian cancer rates continue to increase through the years after 60, the CA 125 test is among the tests most often denied by Medicare.

Most importantly, you need to keep in touch with your own body. Be aware of any changes or repeated occurrences such as:

Feeling of fullness in your abdomen or pelvis,
Frequent urination,
Achy, diffuse pain or discomfort in the abdomen or pelvis,
Weight changes,
Bloating, increasing waistline,
Indigestion, constipation, diarrhea,
Internal pain or pressure during intercourse,
Low back pain,
Unusual vaginal bleeding.

Should you experience any of these symptoms, or if you are in a higher risk category due to family, personal history, age, or other factors, insist that your primary health care provider give you a thorough screening, including a rectovaginal pelvic exam; appropriate lab tests, including a CA 125; and a transvaginal ultrasound. This painless test operates the same as the traditional (transabdominal) ultrasound except the transducer wand is placed inside the vagina, providing a clearer and more thorough picture. Women with significant risk factors, such as first degree family history, should be screened more often than the general population.

While the CA 125 marker test has not turned out to be the single definitive detector of ovarian cancer, its contribution to diagnosis should not be ignored. It is another tool the physician can use to help them reach a diagnosis. We, as health consumers, need to be assertive when communicating with our health care providers. If they won’t listen to your concerns seriously, find someone who will.

As for the future, a research team at Northwestern University is working on a device that removes a few cells from an ovary for examination. This test would be similar to the Pap test, which is used to detect cervical cancer. Dr. Bast, co-developer of the CA 125 test, is working on LPA, a new blood test that could detect early ovarian cancer. He and his collagues have identified two genes associated with ovarian cancer, providing another possible avenue for developing diagnostic tools. Perhaps one of these tests, or another undiscovered test will render the CA 125 controversy a moot point. Until then, all women will face the luck of the draw. Will health care providers be a believer in the usefulness of the CA 125 test and offer it as a diagnostic tool? Or will they be one of the many who waits until the patient gets diagnosed, operated upon, and has chemotherapy to use the test to see if the cancer is winning.

The test currently in use today in the U.S. is the CA 125-II. It’s a second generation test that has replaced the original CA 125 test. The newer test is not as susceptible to daily fluctuations in serum levels because it uses two different antibodies to capture the antigen. Though both tests perform the same function, the results are not interchangeable because the CA 125-II test’s results may be a few points higher.

This article was reported by Ivanhoe, who offers Medical Alerts by e-mail every day of the week.

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