What are Tumor Markers?

Tumor markers are substances that can be found in higher than normal amounts in a person's blood, urine, or bodily tissues when they have a specific type of cancer. Some substances are tumor markers for a specific cancer, while others are tumor markers for multiple cancers. Tumor markers can be used in different ways, depending on the specific type of cancer. Most tumor markers can be used to monitor the extent of the disease and the patient’s response to treatment. Some tumor markers can also be used to detect a cancer recurrence, to give doctors an idea of the prognosis (chance of recovery), to help doctors with treatment-planning, to confirm a diagnosis (in conjunction with other tests), and/or to screen for cancer in undiagnosed individuals.

Tumor markers are not perfect. Not all cancers produce tumor markers. High levels of a tumor marker do not necessarily mean you have cancer, and low levels do not necessarily mean you do not have cancer. Elevated levels of tumor markers may be caused by other types of cancer and non-cancerous diseases. In some cancers, tumor markers are not detectable until an advanced stage. Additionally, tumor markers behave differently in different patients. Two patients with the same levels of tumor markers in the blood could be at very different stages of the disease.

Prostate-specific antigen (PSA)

• Tumor Type(s): Prostate
• Tissue Sample: Blood
• Description: Doctors use this test to screen for prostate cancer in men without symptoms and to help diagnose the disease when symptoms are present. PSA is a protein produced by the prostate that is found in the semen and blood. This test measures the amount of PSA in the blood. If PSA is above a certain level, the doctor may recommend a biopsy. Higher-than-normal amounts of PSA may be caused by cancer or other conditions such as BPH and prostatitis. High PSA levels may also mean the cancer has spread outside of the prostate to other parts of the body. During treatment, PSA levels should begin to decrease. After treatment, PSA should drop to very low or undetectable levels. If PSA levels begin to increase again, then a cancer recurrence is possible.
  When the blood sample is examined, three different measures of PSA may be analyzed:
  • Free PSA: PSA is a protein that circulates in the blood either by binding to other proteins or on its own. Free PSA is the protein that travels alone; it is not bound to any other proteins.
  • Complex PSA: PSA in the blood that is "complexed" or bound to other proteins. This protein circulates in the blood while bound to other proteins.
  • Total PSA: This is the PSA that is most commonly referred to. This is the measue of all PSA in the blood sample, making it a combination of free and complex PSA.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results: The normal range for PSA is 0 – 4 ng/mL. Healthy men usually have a PSA level below 4; however, some men with a PSA level below 4 may have cancer, and some men with a PSA level above 4 may not have cancer.

• Reviewed by: Christopher G. Wood, MD, FACS

Beta-human Chorionic Gonadotropin (ß-hCG)

• Primary Tumor Type: Testicular, Ovarian, Gestational Trophoblastic Disease
• Secondary Tumor Type(s): Liver, Stomach, Lung, Breast, Skin, Bladder
• Tissue Sample: Blood
• Description: Beta-hCG is a hormone normally found in the blood and urine of women only during pregnancy. However, it may also be found in high amounts in patients with certain types of cancer. Measuring the amount of the tumor marker ß-hCG in the blood of cancer patients may help to diagnose cancer and find how well cancer treatment is working. A serum tumor marker test for ß-hCG is done by taking a sample of and examining blood to measure if there are increased levels of ß-hCG present. Increased levels in ß-hCG may also help doctors determine which type of testicular cancer is present. For example, non-seminomas may raise AFP and/or hCG levels, while pure seminomas occasionally raise hCG levels but never AFP levels. If present, the increased levels of ß-hCG will be seen in germ cell tumors which can be found in the egg-producing cells of the ovaries or the cells within the testicles that make sperm and account for more than 90% of testicular cancers.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results: In men and non-pregnant women, the hCG level is normally undetectable. When the test is used as a tumor marker, an elevated hCG level may mean that an individual has a germ cell tumor.
  During treatment for a germ cell tumor, a falling hCG level generally indicates that the condition is responding to therapy. An increased hCG level after treatment may indicate recurrence of disease.

• Reviewed by: Christopher G. Wood, MD, FACS

Carcinoembryonic Antigen (CEA)

• Primary Tumor Type: Colorectal
• Secondary Tumor Type(s): Appendix, Stomach, Gallbladder, Bile Duct, Breast, Mucinous type tumor of any origin
• Tissue Sample: Blood
• Description: The tumor marker for most colorectal cancers is carcinoembryonic antigen (CEA) and is elevated in 50-70% of all colorectal cancer patients. This tumor marker can help doctors monitor the patient’s response to treatment, and check for a recurrence. It is not used to screen for the development of colorectal cancer. After surgery for colorectal cancer, CEA levels usually return to normal. If not, it could mean that the disease is still present. During chemotherapy, decreasing CEA levels indicate that the treatment is likely working, and increasing CEA levels mean it may be getting worse. Your doctor may draw blood every two to three months for the first three years after treatment to monitor for changes in the level of CEA in your blood. Small fluctuations in CEA may occur while on chemotherapy. CEA levels may also help the doctor determine the prognosis, as CEA is usually more elevated in advanced disease.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results:
  • The normal range for CEA is 0 – 5 ng/mL. Slightly elevated levels may be caused by smoking. The normal range for non-smokers is 0 – 2.5 ng/mL, and the normal range for smokers is 0 – 5 ng/mL.
  • Elevated CEA levels may be caused by other cancers (gallbladder, bile duct, stomach, breast, others) and diseases (irritable bowel syndrome, pancreatitis, pneumonia, others). CEA levels above 10 are more likely to be caused by cancer. CEA levels above 20 are very likely to be caused by cancer, and may indicate an advanced cancer that has spread or metastasized.

• Reviewed by: Cathy Eng, MD, FACP

CA-125

• Primary Tumor Type(s): Ovarian, Primary Peritoneal, Fallopian Tube
• Secondary Tumor Type: Uterine
• Tissue Sample: Blood
• Description: CA-125 is a protein made by ovarian cancer cells and normal peritoneum and is a tumor marker for ovarian cancer. CA-125 levels may be higher than normal in women with ovarian cancer. This test alone can't find ovarian cancer. High levels of CA-125 do not necessarily mean you have ovarian cancer and low levels of CA-125 do not necessarily mean you do not. CA-125 may also be elevated in other non-cancerous conditions such as pregnancy, endometriosis, pelvic infection, fibroids, cirrhosis, pancreatitis, ovarian cysts, and others. This test is most useful for detecting recurrent ovarian cancer and monitoring treatment progress. CA-125 can also be used to screen for ovarian cancer in women with Hereditary Breast and Ovarian Cancer Syndrome (HBOCS).
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results:
  • The normal range for CA-125 is 0 to 35 units/mL. About 80-85% of women with ovarian cancer have elevated CA-125 levels.
  • When monitoring treatment progress, the doctor will take a blood sample and have it tested for CA-125 every 2-3 weeks during treatment. If CA-125 levels are still elevated after treatment, the disease may still be present in the body. If CA-125 levels fall, then the tumor may be shrinking and responding well to treatment.
  • During follow-up care for ovarian cancer the doctor will typically periodically test the level of CA-125 in the blood. In many cases of recurrent ovarian cancer, CA-125 levels become elevated 2-6 months before the patient experiences any signs or symptoms.
  • Women with a condition known as Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) have a much higher risk for developing ovarian cancer. These women will be monitored with pelvic examination, transvaginal ultrasound, and CA-125 blood tests every 6 months beginning at age 30.

• Reviewed by: Shannon N. Westin, MD, MPH, FACOG

Alpha Fetoprotein (AFP)

• Tumor Type(s): Liver, Testicular, Ovarian (germ cell)
• Tissue Sample: Blood
• Description: AFP is a protein made in a developing human fetus, and AFP levels decrease after birth. Elevated AFP levels may indicate the presence of liver cancer or testicular cancer (non-seminoma). AFP is mainly used to monitor a patient’s response to treatment and detect cancer recurrence after treatment. AFP is used in a similar way for both liver cancer and testicular cancer. About 60-70% of people with liver cancer and 50-70% of people with non-seminoma testicular cancer have elevated AFP levels.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results:
  • A normal AFP level in the blood is 0 – 15 ng/mL for men and non-pregnant women. Elevated AFP levels may be caused by cancer and other non-cancerous conditions such as cirrhosis, hepatitis, other liver diseases, pregnancy, and inflammatory bowel disease.
  • Generally, AFP levels above 400-500 ng/mL are caused by cancer.
  • In monitoring treatment response, the doctor will test the level of AFP in the blood before surgery. After the tumor is removed, the AFP level should fall. If it doesn’t fall, it means the cancer is still present.
  • After the cancer is removed, the doctor will continue to monitor AFP levels with routine follow-up examinations. If AFP levels rise again, it could indicate a recurrence.

• Reviewed by by: Christopher G. Wood, MD, FACS

CA 19-9

• Primary Tumor Type(s): Pancreatic, Gallbladder, Bile Duct
• Secondary Tumor Type(s): Appendix, Colorectal, Esophageal, Stomach, Liver, and others.
• Tissue Sample: Blood
• Description: CA 19-9 is an antigen that is normally produced in small amounts by the pancreas and biliary ductal cells, gastrointestinal tract, and others. Cancer in any of these organs can cause elevated levels of CA 19-9. High levels of CA 19-9 do not mean you have cancer, and low levels do not necessarily mean you do not. CA 19-9 can not be used to diagnose the disease, but can be used to monitor the effectiveness of treatment and/or to detect a recurrence. Higher-than-normal amounts of CA 19-9 may also be caused by other non-cancerous conditions such as inflammation or infection among others, so it is not a reliable indicator of cancer.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results:
  • The normal, healthy range of CA 19-9 in the blood is 0 – 37 units/mL. About 80% of pancreatic cancer patients have a CA 19-9 level above 37. Very high CA 19-9 levels above 1000 units/mL may indicate an advanced tumor.
  • In monitoring treatment response, the doctor will test the level of CA 19-9 in the blood every 1-3 months during treatment. A fall of CA 19-9 levels could mean that the tumor is responding well to treatment.
  • After surgery and adjuvant therapy to remove the tumor, CA 19-9 levels should fall. If CA 19-9 levels rise again, it could mean the cancer has come back.
  • NOTE: CA 19-9 can be elevated in many benign conditions like pancreatitis or jaundice, in the absence of cancer. In pancreatic cancer or biliary cancer, stent blockade can cause CA 19-9 to increase. Any such elevation should be discussed with the medical team and does not necessarily imply that is coming from cancer.

Reviewed by:

• Miguel A. Rodriguez-Bigas, MD, FACS, FASCRS
• Milind Javle, MD

CA 15-3

• Tumor Type(s): Breast
• Tissue Sample: Blood
• Description: CA 15-3 is a protein made by breast cancer cells that may be elevated in women with advanced breast cancer. CA 15-3 is not usually elevated in early-stage breast cancer. For breast cancer, the doctor may also test the levels of the tumor markers CA 27.29 and CEA. CA 15-3 is mainly used to monitor response to treatment for advanced breast cancer. A decrease of CA 15-3 levels may mean that the treatment is working, and an increase in CA 15-3 levels may mean the tumor is growing or spreading. Higher-than-normal amounts of CA 15-3 may also be caused by non-cancerous conditions such as inflammation or infection, so it is not a reliable indicator of cancer detection. Use of this tumor marker must be carefully coordinated with your primary medical oncologist.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results: The normal range of CA 15-3 is 0 – 30 units/mL. CA 15-3 is elevated in about 80% of metastatic breast cancers.

• Reviewed by: Naoto T. Ueno, MD, PhD

CA 27.29

• Tumor Type(s): Breast
• Tissue Sample: Blood
• Description: CA 27.29 is a protein produced by breast cancer cells and that may be elevated in women with breast cancer. Like CA 15-3, CA 27.29 is most useful in cases of advanced breast cancer, and is not often elevated in early stages. For breast cancer, the doctor may also test the levels of the tumor markers CA 15-3 and CEA. CA 27.29 is used to monitor the patient’s response to treatment. A drop in CA 27.29 levels may mean the treatment is working, and a rise may mean that the tumor is growing or spreading. CA 27.29 is not useful in helping to diagnose or stage the disease, or in detecting a cancer recurrence. Higher-than-normal amounts of CA 27.29 may also be caused by non-cancerous conditions such as inflammation or infection, so it is not a reliable indicator of cancer. Use of this tumor marker must be carefully coordinated with your primary medical oncologist.
• Test Procedure: Blood is drawn from the arm and sent to a laboratory for analysis.
• Test Results: The normal range of CA 27.29 is 0 – 38 units/mL.

• by

  
  reviewed by: Naoto T. Ueno, MD, PhD

Circulating Tumor DNA (ctDNA)

• Tumor Type(s): Pancreatic, Colorectal, Breast, Lung
• Tissue Sample: Blood or other bodily fluids (urine, cerebrospinal fluid, or saliva)
• Description: Although most liquid biopsies are not yet used in routine clinical care, numerous researchers believe that in the near future liquid biopsies may be used as less invasive alternative to tissue biopsies. Tissue biopsies may be costly, risky and incredibly painful, making it difficult to perform numerous biopsies on a single patient. Liquid biopsies are less invasive and rely on tumor materials released into the bloodstream. Thus, physicians are capable of tracking tumors as they develop and change before, during and after the treatment of cancer. Dying tumor cells shed molecules and cells containing their DNA into the bloodstream. Most cancer cells carry DNA mutations that are only present in tumor cell DNA and therefore provide incredibly specific biomarkers. These cells and molecules are known as circulatory tumor DNA or ctDNA. When used as a liquid biopsy biomarker, ctDNA has proven to be extremely effective. Recent studies have shown that ctDNA-based liquid biopsies may be used to track cancer development, understand patient response to treatment, and monitor patients at high risk of recurrence. Because these tests provide molecular information about a patient's individual cancer, which can change at any point during the course of the cancer, physicians are capable of creating more personalized treatment plans. Physicians may also be able to better monitor patient response and make adjustments to treatment in real time. Numerous studies have shown the advantages associated with ctDNA-based liquid biopsies, however more are to be done to determine if these tests improve overall patient outcomes before they are implemented into clinical care.
• Test Procedure:Blood is drawn from the arm. It is sent to a laboratory for measurement of the levels of ctDNA in the blood. A liquid biopsy is performed rather than a tissue biopsy.
• Test Results:The amount of ctDNA in the blood sample may have a variety of explanations. In some cases, it has been shown that a greater amount of ctDNA present in the blood indicates a more advanced cancer. Results of liquid biopsies may also provide molecular information about the cancer that may allow for physicians to create more personalized treatment plans for patients.

• Reviewed by: Cathy Eng, MD, FACP