The tumour markers CA-125 and CEA

(Aotea News, March 2009)

Dr Michael Crooke
Aotea Pathology
Clinical Biochemist

These two tumour markers can cause considerable trouble if ordered inappropriately.

CA-125 has a use for monitoring patients with known ovarian cancer, or in the investigation of a pelvic mass, but it can be difficult to interpret and is best used in specialist practice.

In general practice there may be temptation to use the test for screening in women without any particular risk factors, especially in the anxious patient who may have seen some of the misinformation circulating by e-mail or on the internet. This practice will lead to most unwelcome problems.

Screening for ovarian cancer with CA-125 in women at average risk is not recommended in any published guideline because the test has such poor sensitivity and specificity.

The sensitivity for early ovarian cancer is only about 50%, so a result within the reference interval cannot be used as a rule out test.

Although ovarian cancer is a very serious condition, it occurs at a relatively low frequency. Thus a true positive result will be rare. CA-125 is nonspecific, being raised by fluctuation within the menstrual cycle, benign ovarian cysts, fibroids, endometriosis, pelvic inflammatory disease and a wide range of other benign conditions. Collectively, these conditions occur at a much higher frequency than ovarian cancer.

Thus most positive results in women at average risk will be false positives and the predictive value will be very low, far from the standards required for a screening test.

The role of symptom recognition is important in guiding a more reasonable approach to early detection of ovarian cancer.

Persistent [almost daily] symptoms of bloating, pelvic or abdominal pain, early satiety or urinary symptoms are most useful and should prompt full investigation, including both CA-125 and transvaginal ultrasound. CA-125 by itself is insufficient because of the poor sensitivity.

Screening in asymptomatic women may be done if there is family history of ovarian cancer, although even then there is no clear evidence of usefulness and protocols are not yet well defined. If CA-125 is ordered in such circumstances it should be in conjunction with a transvaginal ultrasound and there are trials of this strategy in progress.

The nature of the family history is important. If there is a sporadic case in another first or second degree relative the risk is increased by about 3 fold to a lifetime risk of about 5%. In the case of a very strong family history the question of a genetic syndrome may arise and women with mutations in either the BRAC1 or BRAC2 gene have a lifetime risk of 40-50% for ovarian cancer, as well as high risk of breast or bowel cancer.

Genetic counselling and mutation analysis is recommended in women from families with this familial syndrome, with annual CA-125 and ultrasound if mutation positive.

CEA has similar limitations. In specialist practice, the test is used as a follow up to monitor for recurrence of colorectal cancer in those who have had surgical resection with potential cure. Initial and subsequent levels also may have a role in assessing prognosis but preoperative levels should not be used to select patients for adjuvant therapy.

There is also a role in monitoring treatment of advanced disease.

Of more relevance to general practice, all authorities recommend against attempting to use CEA as a screening test for colorectal cancer, even in those with suggestive signs and symptoms.

The sensitivity of the test is much too low for this purpose and symptomatic patients require colonoscopy irrespective of levels of CEA. Non-specific elevations are common and levels tend to be higher in smokers and to show minor increases with age.