Dr. E. Brydon, Practicing Gynecological Oncologist, Regina
Information for the general public on the use of CA 125 as a screening test is found in many publications and on the internet. Many female patients are now requesting routine screening of AC 125 as part of a routine physical examination. Dr. Betsy Brydon, who practices as a gynecological oncologist in Regina has written this brief physician update to provide some information to enable physicians to assist their patients in deciding whether this test is appropriate for them.
The protein CA125 is found in normal human blood in small amounts. It has been found to vary in level from person to person, but in the vast majority the level of below 35 U/ml. Therefore, the cutoff level for "normal" has been arbitrarily set at 35.
CA 125 is a protein that is produced in response to irritation of the surfaces of the body cavities. Anything that irritates the peritoneal cavity, the pleural cavity, even the pericardial sac, will cause an elevation of the CA 125. Thus, there are many benign conditions that will cause an elevation in the level of CA 125. Some of these conditions are gynecological: endometriosis, fibroids, and even menstruation. Other diseases that are not malignant but can cause an elevation are cirrhosis of the liver, pneumonia and congestive heart failure. Other cancers besides ovarian can cause an elevation, for example, colon cancer metastatic to the peritoneal cavity, metastatic stomach cancer and pancreatic cancer.
With respect to ovarian cancer, the elevations of CA 125 can be extremely high, into the thousands, although the degree of elevation does not necessarily correlate with the volume of disease. With ovarian cancer, a CA 125 of more than one thousand is associated with a poorer prognosis than an ovarian cancer with a level of less than one thousand. Fifteen per cent of the common epithelial ovarian cancers (most of these the mucinous sub-type) do not express CA 125 al all. More importantly, only 50% of ovarian tumors express any elevation in the CA 125 while the cancer is still limited to the ovary, (stage 1A), the only stage at which cure is often possible.
CA 125 is used clinically to follow the treatment results for women who have ovarian cancer where treatment is underway and in whom there is an elevation of CA 125. However, it is a difficult test to work with clinically. While women are undergoing treatment, the rapidity of the fall in the level of the CA 125 is a predictor of response to treatment and the subsequent disease-free interval. In the event of an elevation in the CA 125 following treatment, this will usually occur while the women is still asymptomatic, and there is no literature to suggest that treating the recurrence at the time of elevation in the CA 125, while there are yet no symptoms and no clinical signs of recurrence, will improve survival time. Thus, the patient will be understandable anxious about recurrent while she is yet well. The lag time from the elevation to clinical disease can be over a year and is usually several months. Given the lack of evidence is it a service to them and to their lives to follow the CA 125?
As with thyroid hormone, each individual has their own normal level for CA 125. Therefore changes in the individual's level are of more significance than the actual value. An "abnormal" value must result in a search for the reason. At the very least this will involve a physical exam, an ultrasound, and if negative, a CT scan of the abdomen and pelvis. Some of us are aware of someone who had an elevation of CA 125 on a screening test and was subsequently found to have an ovarian cancer. But much more frequent are those who have an elevation on screning, but no reason is found after numerous investigations and untold anxiety to the patient. Currently no cancer society recommends the routine use of CA 125 screening.