TUMOR MARKERS & CANCER SCREENING

KENYA NATIONAL CANCER SCREENING GUIDELINES I 107

TUMOR MARKERS & CANCER SCREENING

Introduction

Tumor markers are chemical substances in the body that are either produced by a can-

cer or by the body in response to a cancer. They are found mainly in blood, but also in

urine and other body fluids of some people with certain cancers. They are also known

as biomarkers.

Measuring the tumor markers can allow for determination of whether a particular type of cancer is actively growing (and thus producing the corresponding tumor marker). Most tumor markers are proteins or carbohydrate-proteins. More recently, there are also genetic molecules (DNA, RNA) serving as tumor markers. They are based on genetic changes associated with certain cancers.

There are many molecules that have been discovered to be associated with various can- cers, but not all are used in the clinical setting because they fail to meet the criteria for such use. For molecules to be used reliably as tumor markers, they have to be both highly sensitive and specific:

• Sensitive: Able to detect presence of tumor even at low volume/low count,

hence minimizing false negative results.

• Specific: Only found in the presence of the tumor and not in people who don’t

have the tumor. This means there it will not result in false positives, which can

cause undue stress for healthy patients.

USE OF TUMOR MARKERS IN CANCER CARE

Tumor marker tests may be useful for a number of purposes in cancer care. These in- clude early detection, diagnosis, and management, including guiding appropriate treat- ment, staging, determining prognosis, monitoring response to treatment and monitor- ing disease recurrence. They are usually not used in isolation but in combination with other tests, since they are not definitive but provide additional information which can be helpful in various ways.

Regarding recurrence, once a particular tumor marker has been found to be elevated in a patient with a particular cancer before treatment, it can be used to monitor for re- currence of the cancer after treatment is completed. Some tumor markers may help to detect a recurrence sooner than other tests.

108 I KENYA NATIONAL CANCER SCREENING GUIDELINES

Different tumor markers may be used for different cancers, such as tabulated below:

TUMOR MARKER ASSOCIATED CANCER USES
AFP (Alpha feto protein) Liver Diagnosis

Monitoring disease progression &

response to treatment

Testicular cancer Diagnosis

Monitoring response to treatment

CA 15 3 (Cancer antigen Breast Monitoring disease progression &
15-3) response to treatment
Assessing recurrence
CA 19 9 (Cancer antigen

19-9)

Pancreatic cancer Diagnosis

Staging

Monitoring disease progression &

response to treatment

CA 125 (Cancer antigen

125)

Ovarian Early detection*

Monitoring disease progression &

response to treatment

Calcitonin Medullary thyroid cancer Diagnosis

Monitoring disease progression &

response to treatment

Assessing recurrence

CEA (Carcinoembryonic Colorectal

antigen)

Staging

Monitoring disease progression &

response to treatment

Assessing recurrence

HCG (Human chorionic Testicular Diagnosis

Staging

Monitoring disease progression &

response to treatment

Assessing recurrence

gonadotropin)

Trophoblastic disease

Choriocarcinoma
PSA

antigen)

(prostate specific Prostate Early detection*

Diagnosis

Monitoring disease progression &

response to treatment

Molecular Tests
EFGR (Epidermal Growth Lung To guide treatment & determine

prognosis

Factor Receptors)
KRAS Colon, lung To guide treatment
BCR-ABL CML (Chronic Myeloid Diagnosis, monitoring treatment &

Leukaemia) detecting recurrence

*in very restricted settings as explained below

There is a lot of ongoing research on many other potential tumor markers.

LIQUID BIOPSY

This refers to a new approach that involves the use of blood or other body fluids as a specimen to detect genes produced by a tumor. It is being shown to have a high sensitivity in detecting the presence of a tumor and therefore allowing early diagnosis and hence improving the success of treatment. Just like the other tumor markers, their absence does not exclude the presence of the corresponding cancer. Examples include EGFR for non-small cell lung cancer, KRAS for colon cancer and BRCA1 for breast can- cer. Research is still underway to determine the usefulness of liquid biopsies in cancer screening in the general population.

LIMITATIONS FOR USE OF TUMOR MARKERS

The use of tumor markers is limited by a number of factors. First, not all cancers of a particular type produce the associated tumor marker – some patients with a particular cancer type may not have elevated levels of the associated tumor marker even if the type of cancer they have usually make the particular tumor marker. Secondly, a tumor marker may not be exclusive to a particular type of cancer- different types of cancers may produce the same tumor marker. For example, CEA is associated with colon cancer, but may also be produced by other cancers such as lung, breast, thyroid, pancreatic, liver, cervix, and bladder cancers. Also, some noncancerous conditions can also be as- sociated with high levels. of tumor markers. E.g. Benign ovarian cysts – CA-125; Colon obstruction- CEA and bile duct obstruction – CA 19-9. Further, not all cancers produce tumor markers that have been identified with them.

TUMOR MARKERS IN CANCER SCREENING

Most tumor markers have NO ROLE IN CANCER SCREENING in the general population

Presently, most tumor markers have NO ROLE in cancer screening in the general popu- lation. Screening involves the use of medical evaluation (in this case a laboratory test) to detect a cancer before it has developed. Since tumor markers are produced by can- cers or by the body in response to cancer, there is no tumor marker that can be used for screening. In addition, most tumor markers are neither sensitive nor specific enough to be used on their own to screen for cancer. This means that their use would result in too many false positives resulting in harmful effects such as anxiety, need for expensive and unnecessary follow-up tests.

However, there is a role for tumor markers in detecting cancers early before they be- come symptomatic. Since some patients with a particular cancer may not express the corresponding tumor marker, and some patients who do not have a particular cancer may still have elevated levels of the tumor marker due to other conditions that are not cancer, the use of tumor markers in early detection of cancer is VERY RESTRICTED. Very few tumor markers are thus useful for this, and in limited settings. They can be used for screening high risk individuals with either a strong family history or with specific risk factors for a particular cancer, including:

1. PSA

Refer to Prostate Cancer Screening guidelines, Pages 84 – 94

2. CA 125

For early detection of ovarian cancer in females with a positive family history or with abdominal masses.

How often to test: The frequency of follow up has not yet been determined and there are no established guidelines yet.

A raised CA 125 does not equate to having cancer. Biopsy is needed for definitive diagnosis.

No evidence supports the use of CA 125 to screen the general population for ovarian cancer.

WHEN TO USE TUMOR MARKERS

Unfortunately, tumor markers are often misused in the guise of screening by unscrupulous

persons claiming that they can detect cancer early, whereas that is but a false notion. Some

of the tumor markers that are commonly misused are AFP, CA 15-3, CA 19-9, Calcitonin, CEA

and hCG. Their appropriate uses are as indicated earlier.

Tumor markers can be used to promote prompt diagnosis during clinical evaluation in cases where there is a high index of suspicion at the point of contact with the patient. They can be used as an aid to clinical diagnosis because they are relatively inexpensive and accessible (compared to radiology and biopsy). They can also be used for early detection of recurrence.

It must be noted though that the presence or elevated levels of a tumor marker alone is not enough to diagnose cancer. Furthermore, tumor markers are only useful in patients with cancers expressing the tumor markers, therefore a negative result for a tumor markers test does not exclude the presence or recurrence of the cancer.

REFERENCES

American Society of Clinical Oncology (ASCO): Tumor Marker Tests. (2018, June 15). Retrieved October 18, 2018, from https://www.cancer.net/navigating-cancer-care/di- agnosing-cancer/tests-and-procedures/tumor-marker-tests

American Society of Clinical Oncology (ASCO): Tumor Marker Tests. (2018, June 15). Retrieved October 18, 2018, from https://www.cancer.net/navigating-cancer-care/di- agnosing-cancer/tests-and-procedures/tumor-marker-tests

Australasian Association of Clinical Biochemists (AACB): Tumour markers. (n.d.). Re- trieved October 18, 2018, from https://www.labtestsonline.org.au/learning/test-in- dex/tumour-markers

National Cancer Institute: Tumor Markers. (n.d.). Retrieved October 18, 2018, from https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers- fact-sheet

American Society of Clinical Oncology

 

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