CMS Pub. 100-03, ch. 1, § 190.28

Immunoassay determinations of the serum levels of certain proteins or carbohydrates

serve as tumor markers. When elevated, serum concentration of these markers may

reflect tumor size and grade.

This policy specifically addresses tumor antigen CA 125.

Indications

The CA 125 is a high molecular weight serum tumor marker elevated in 80 percent of

patients who present with epithelial ovarian carcinoma. It is also elevated in carcinomas

of the fallopian tube, endometrium, and endocervix. An elevated level may also be

associated with the presence of a malignant mesothelioma or primary peritoneal

carcinoma.

A CA 125 level may be obtained as part of the initial pre-operative work-up for women

presenting with a suspicious pelvic mass to be used as a baseline for purposes of post-operative monitoring. Initial declines in CA 125 after initial surgery and/or

chemotherapy for ovarian carcinoma are also measured by obtaining three serum levels

during the first month post treatment to determine the patient’s CA 125 half-life, which

has significant prognostic implications.

The CA 125 levels are again obtained at the completion of chemotherapy as an index of

residual disease. Surveillance CA 125 measurements are generally obtained every 3

months for 2 years, every 6 months for the next 3 years, and yearly thereafter. CA 125

levels are also an important indicator of a patient’s response to therapy in the presence of

advanced or recurrent disease. In this setting, CA 125 levels may be obtained prior to

each treatment cycle.

Limitations

These services are not covered for the evaluation of patients with signs or symptoms

suggestive of malignancy. The service may be ordered at times necessary to assess either

the presence of recurrent disease or the patient’s response to treatment with subsequent

treatment cycles.

The CA 125 is specifically not covered for aiding in the differential diagnosis of patients

with a pelvic mass as the sensitivity and specificity of the test is not sufficient. In

general, a single “tumor marker” will suffice in following a patient with one of these

malignancies.

(This NCD last reviewed November 2005)

190.29 - Tumor Antigen by Immunoassay CA 15-3/CA 27.29

(Rev. 17, Issued: 07-02-04) (Effective/Implementation: Not Applicable)

PM AB-02-110

Immunoassay determinations of the serum levels of certain proteins or carbohydrates

serve as tumor markers. When elevated, serum concentration of these markers may

reflect tumor size and grade. This policy specifically addresses the following tumor

antigens: CA 15/3 and CA 27.29

Indications

Multiple tumor markers are available for monitoring the response of certain malignancies

to therapy and assessing whether residual tumor exists post-surgical therapy.

CA 15-3 is often medically necessary to aid in the management of patients with breast

cancer. Serial testing must be used in conjunction with other clinical methods for

monitoring breast cancer. For monitoring, if necessary, use consistently either CA 15-3

or CA 27.29, not both.

CA 27.29 is equivalent to CA 15-3 in its usage in management of patients with breast

cancer.

Limitations

These services are not covered for the evaluation of patients with signs or symptoms

suggestive of malignancy. The service may be ordered at time necessary to assess either

the presence of recurrent disease or the patient’s response to treatment with subsequent

treatment cycles.

190.30 - Tumor Antigen by Immunoassay CA 19-9

(Rev. 17, Issued: 07-02-04) (Effective/Implementation: Not Applicable)

PM AB-02-110

Immunoassay determinations of the serum levels of certain proteins or carbohydrates

serve as tumor markers. When elevated, serum concentration of these markers may

reflect tumor size and grade. This policy specifically addresses the following tumor

antigen: CA 19-9.

Indications

Multiple tumor markers are available for monitoring the response of certain malignancies

to therapy and assessing whether residual tumor exists post-surgical therapy.

Levels are useful in following the course of patients with established diagnosis of

pancreatic and biliary ductal carcinoma. The test is not indicated for diagnosing these

two diseases.

Limitations

These services are not covered for the evaluation of patients with signs or symptoms

suggestive of malignancy. The service may be ordered at times necessary to assess either

the presence of recurrent disease or the patient’s response to treatment with subsequent

treatment cycles.

190.31 - Prostate Specific Antigen

(Rev. 17, Issued: 07-02-04) (Effective/Implementation: Not Applicable)

PM AB-02-110

Prostate Specific Antigen (PSA), a tumor marker for adenocarcinoma of the prostate, can

predict residual tumor in the post-operative phase of prostate cancer. Three to six months

after radical prostatectomy, PSA is reported to provide a sensitive indicator of persistent

disease. Six months following introduction of antiandrogen therapy, PSA is reported as

capable of distinguishing patients with favorable response form those in whom limited

response is anticipated.

The PSA when used in conjunction with other prostate cancer tests, such as digital rectal

examination, may assist in the decision making process for diagnosing prostate cancer,

PSA also, serves as a marker in following the progress of most prostate tumors once a

diagnosis has been established. This test is also an aid in the management of prostate

cancer patients and in detecting metastatic or persistent disease in patients following

treatment.

Indications

The PSA is of proven value in differentiating benign from malignant disease in men with

lower urinary tract signs and symptoms (e.g., hematuria, slow urine stream, hesitancy,

urgency, frequency, nocturia and incontinence) as well as with patients with palpably

abnormal prostate glands on physician exam, and in patients with other laboratory or

imaging studies that suggest the possibility of a malignant prostate disorder. PSA is also

a marker used to follow the progress of prostate cancer once a diagnosis has been

established, such as in detecting metastatic or persistent disease in patients who may

require additional treatment. PSA testing may also be useful in the differential diagnosis

of men presenting with as yet undiagnosed disseminated metastatic disease.

Limitations

Generally, for patients with lower urinary tract signs or symptoms, the test is performed

only once per year unless there is a change in the patient’s medical condition.

Testing with a diagnosis of in situ carcinoma is not reasonably done more frequently than

once, unless the result is abnormal, in which case the test may be repeated once.

190.32 - Gamma Glutamyl Transferase

(Rev. 17, Issued: 07-02-04) (Effective/Implementation: Not Applicable)

PM AB-02-110

Gamma glutamyltransferase (GGT) is an intracellular enzyme that appears in blood

following leakage from cells. Renal tubules, liver, and pancreas contain high amounts,

although the measurement of GGT serum is almost always used for assessment of

hepatobiliary function. Unlike other enzymes, which are found in heart, skeletal muscle,

and intestinal mucosa as well as liver, the appearance of an elevated level of GGT is

serum is almost always the result of liver disease or injury. It is specifically useful to

differentiate elevated alkaline phosphatase level when the source of the alkaline

phosphatase increase (bone, liver, or placenta) is unclear. The combination of high

alkaline phosphatase and a normal GGT does not, however, rule out liver disease

completely.

As well as being a very specific marker of hepatobiliary function, GGT is also a very

sensitive marker for hepatocellular damage. Abnormal concentrations typically appear

before elevations of other liver enzymes or bilirubin are evident. Obstruction of the

biliary tract, viral infection (e.g., hepatitis, mononucleosis), metastatic cancer, exposure

to hepatotoxins (e.g., organic cimetidine, barbiturates, phenytoin, and carbamazepine) all

can cause a moderate to marked increase in GGT serum concentration. In addition, some

drugs can cause or exacerbate liver dysfunction (e.g., atorvastatin, troglitazone, and

others as noted in FDA Contraindications and Warning.)

The GGT is useful for diagnosis of liver disease or injury, exclusion of hepatobiliary

involvement related to other disease, and patient management during the resolution of

existing disease or following injury.

Indications

1. To provide information about known or suspected hepatobiliary disease, for

example:

a. Following chronic alcohol or drug ingestion

b. Following exposure to hepatotoxins

c. When using medication known to have a potential for causing liver

toxicity (e.g., following the drug manufacturer’s recommendations)

d. Following infection (e.g., viral hepatitis and other specific infections

such as amebiasis, tuberculosis, psittacosis, and similar infections)

2. To assess liver injury/function following diagnosis of primary or secondary

malignant neoplasms

3. To assess liver injury/function in a wide variety of disorders and diseases

known to cause liver involvement (e.g., diabetes mellitus, malnutrition, disorders of

iron and mineral metabolism, sarcoidosis, amyloidosis, lupus and hypertension)

4. To assess liver function related to gastrointestinal disease

5. To assess liver function related to pancreatic disease

6. To assess liver function in patients subsequent to liver transplantation

7. To differentiate between the different sources of elevated alkaline phosphatase

activity

Limitations

When used to assess liver dysfunction secondary to existing non-hepatobiliary disease

with no change in signs, symptoms, or treatment, it is generally not necessary to

repeat a GGT determination after a normal result has been obtained unless new

indications are present.

If the GGT is the only “liver” enzyme abnormally high, it is generally not necessary

to pursue further evaluation for liver disease for this specific indication.

When used to determine if other abnormal enzyme tests reflect liver abnormality

rather than other tissue, it generally is not necessary to repeat a GGT more than one

time per week.

Because of the extreme sensitivity of GGT as a marker for cytochrome oxidase

induction or cell membrane permeability, it is generally not useful in monitoring

patients with known liver disease.

190.33 - Hepatitis Panel/Acute Hepatitis Panel

(Rev. 17, Issued: 07-02-04) (Effective/Implementation: Not Applicable)

PM AB-02-110

This panel consists of the following tests:

• Hepatitis A antibody (HAAb), IgM antibody;

• Hepatitis B core antibody (HBcAb), IgM antibody;

• Hepatitis B surface antigen (HBsAg) and;

• Hepatitis C antibody;

Hepatitis is an inflammation of the liver resulting from viruses, drugs, toxins, and

other etiologies. Viral hepatitis can be due to one of at least five different viruses,

designated hepatitis A, B, C, and E. Most cases are caused by hepatitis A virus

(HAV), hepatitis B virus (HBV), or hepatitis C virus, (HCV).

The HAV is the most common cause of hepatitis in children and adolescents in the

United States. Prior exposure is indicated by a positive IgG anti-HAV. Acute HAV

is diagnosed by IgM anti-HAV, which typically appears within four weeks of

exposure, and which disappears within three months of its appearance. IgG anti-HAV is similar in the timing of its appearance, but it persists indefinitely. Its

detection indicates prior effective immunization or recovery form infection.

Although HAV is spread most commonly by fecal-oral exposure, standard immune

globulin may be effective as a prophylaxis.

The HBV produces three separate antigen (surface, cores and e (envelope) antigens)

when it infects the liver, although only hepatitis B surface antigen (HBsAg) is

included as part of this panel. Following exposure, the body normally responds by

producing antibodies to each of these antigens; one of which is included in this panel:

hepatitis B surface antibody (HBsAb)-IgM antibody, HBsAg is the earlier marker,

appearing in serum four to eight weeks after exposure, and typically disappearing

within 6 months after its appearance. If HBsAg remains detectable for greater than 6

months, this indicates chronic HBV infection. HBcAb, in the form of both IgG and

IgM antibodies, are next to appear in serum, typically becoming detectable 2-3

months following exposure. The IgM antibody gradually declines or disappears

entirely 1-2 years following exposure, but the IgG usually remains detectable for life.

Because HBsAg is present for a relatively short period and usually displays a low

titer, a negative result does not exclude and HBV diagnosis. HBcAb, on the other

hand, rises to a much higher titer and remain elevated for a longer period of time, but

a positive result is not diagnostic of acute disease, since it may be the result of a prior

infection. The last marker to appear in the course of a typical infection is HBsAb,

which appears in serum 4-6 months following exposure to infected blood or body

fluids; in the U.S., sexual transmission accounts for 30-60 percent of new cases of

HBV infection.

The diagnosis of acute HBV infection is best established by documentation of

positive IgM antibody against the core antigen (HBcAb-IgM) and by identification of

a positive hepatitis B surface antigen (HBsAg). The diagnosis of chronic HBV

infection is established primarily by identifying a positive hepatitis B surface antigen

(HBsAg) and demonstrating positive IgG antibody directed against the core antigen

(HBcAb-IgG). Additional tests such as hepatitis B e antigen (HBeAg) and hepatitis B

e antibody (HBeAb), the envelope antigen and antibody, are not included in the

hepatitis panel, but may be of importance in assessing the infectivity of patients with

HBV. Following completion of a HBV vaccination series, HBsAB alone may be

used monthly for up to 6 months, or until a positive result is obtained, to verify an

adequate antibody response.

HCV is the most common cause of post-transfusion hepatitis; overall HCV is

responsible for 15-20 percent of all cases of acute hepatitis, and is the most common

cause of chronic liver disease. The test most commonly used to identify HCV

measures HCV antibodies, which appear in blood 2-4 months after infection. False

positive HCV results can occur. For example, a patient with a recent yeast infection

may produce a false positive anti-HCV result. For this reason, at present positive

results usually are confirmed by a more specific technique. Like HBV, HCV is

spread exclusively through exposure to infected blood or body fluids.

This panel of tests is used for differential diagnosis in a patient with symptoms of

liver disease or injury. When the time of exposure or the stage of the disease is not

known, a patient with continued symptoms of liver disease despite a completely

negative hepatitis panel may need a repeat panel approximately 2 weeks to 2 months

later to exclude the possibility of hepatitis. Once a diagnosis is established, specific

tests can be used to monitor the course of the disease.

Indications

1. To detect viral hepatitis infection when there are abnormal liver function test

results, with or without signs or symptoms of hepatitis.

2. Prior to and subsequent to liver transplantation.

Limitations

After a hepatitis diagnosis has been established, only individual tests, rather than the

entire panel, are needed.

190.34 - Fecal Occult Blood Test

(Rev. 17, Issued: 07-02-04) (Effective/Implementation: Not Applicable)

PM AB 02-110

The fecal occult blood test (FOBT) detects the presence of trace amounts of blood in

stool. The procedure is performed by testing one or several small samples of one,

two or three different stool specimens.

This test may be performed with or without evidence of iron deficiency anemia,

which may be related to gastrointestinal blood loss. The range of causes for blood

loss include inflammatory causes, including acid-peptic disease, non-steroidal anti-inflammatory drug use, hiatal hernia, Crohn’s disease, ulcerative colitis,

gastroenteritis, strongyloides, ascariasis, tuberculosis, and enteroamebiasis. Vascular

causes included angiodysplasia, hemangiomas, varices, blue rubber bleb nevus

syndrome, and watermelon stomach. Tumors and neoplastic causes include

lymphoma, leiomyosarcoma, lipomas, adenocarcinoma and primary and secondary

metastases to the GI tract. Drugs such as nonsteroidal anti-inflammatory drugs also

cause bleeding. There are extra gastrointestinal causes such as hemoptysis, epistaxis,

and oropharyngeal bleeding. Artifactual causes include hematuria, and menstrual

bleeding. In addition, there may be other causes such as coagulopathies, gastrostomy

tubes or other appliances, factitial causes, and long distance running.

Three basic types of fecal hemoglobin assays exist, each directed at a different

component of the hemoglobin molecule.

1. Immunoassays recognize antigenic sites on the globin portion and are least

affected by diet or proximal gut bleeding, but the antigen may be destroyed by fecal

flora.

2. The heme-porphyrin assay measures heme-derived porphyrin and is least

influenced by enterocolic metabolism or fecal storage. This assay does not

discriminate dietary from endogenous heme. The capacity to detect proximal gut

bleeding reduces its specificity for colorectal cancer screening but makes it more

useful for evaluating overall GI bleeding in case finding for iron deficiency anemia.

3. The guaiac-based test is the most widely used. It requires the peroxidase

activity of an intact heme moiety to be reactive. Positivity rates fall with storage.

Fecal hydration such as adding a drop of water increases the test reactivity but also

increases false positivity.

Of these three tests, the guaiac-based test is the most sensitive for detecting lower

bowel bleeding. Because of this sensitivity, it is advisable, when it is used for

screening, to defer the guaiac-based test if other studies of the colon are performed

prior to the test. Similarly, this test’s sensitivity may result in a false positive if the

patient has recently ingested meat. Both of these cautions are appropriate when the

test is used for screening, but when appropriate indications are present, the test should

be done despite its limitations.

Indications

1. To evaluate known or suspected alimentary tract conditions that might

cause bleeding into the intestinal tract.

2. To evaluate unexpected anemia.

3. To evaluate abnormal signs, symptoms, or complaints that might be

associated with loss of blood.

4. To evaluate patients complaints of black or red-tinged stools.

Limitations

1. The FOBT is reported once for the testing of up to three separate

specimens (comprising either one or two tests per specimen).

2. In patients who are taking non-steroidal anti-inflammatory drugs and have

a history of gastrointestinal bleeding but no other sign, symptoms, or complaints

associated with gastrointestinal blood loss, testing for occult blood may generally be

appropriate no more than once every 3 months.

When testing is done for the purpose of screening for colorectal cancer in the absence of

signs, symptoms, conditions, or complaints associated with gastrointestinal blood loss,

report he HCPCS code for colorectal cancer screening; fecal-occult blood test, 1-3

simultaneous determinations) should be used.