Understanding Tumor Markers: A Guide to Marker Tests in Common Use

In the complex world of oncology and cancer care, the term “tumor marker” often arises, but what does it truly mean?

Tumor markers are substances (most often proteins, but also encompassing enzymes, hormones, and even genetic material) that are produced by cancer cells or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. These biological signals can be found in the blood, urine, stool, cerebrospinal fluid, or the tumor tissue itself. 

Understanding the different types of tumor markers and their distinct roles is crucial for patients and their families navigating a cancer diagnosis.

This article delves deep into the subject of tumor markers, explaining what they are, how they are used, the significant limitations of a tumor marker test, and which marker tests are in common use for various types of cancer.

What Exactly Is a Tumor Marker?

A tumor marker is a biological molecule that provides important information about the presence, type, or behavior of cancer. These substances can be proteins, hormones, enzymes, or fragments of DNA shed by tumor cells, and are often found in higher-than-normal levels in the blood, urine, or tissues of individuals with certain cancers. 

Because different cancers are associated with specific markers, Their presence at unusually high levels can help indicate the existence of a particular type of cancer. Tumor markers are also known as “cancer markers” and can be used not only for diagnosis but also for monitoring treatment effectiveness or detecting cancer recurrence.

Tumor markers are often present at low levels in healthy individuals, as they can play roles in normal cell functions. However, their levels may rise due to cancer (malignant) or non-cancerous (benign) conditions. Because of this, a single elevated reading is not sufficient for a cancer diagnosis. A key feature of a useful tumor marker is that its level reflects the tumor’s burden (such as size, growth, or activity) making it a valuable tool for monitoring disease status. Changes in marker levels can signal progression, regression, or recurrence of cancer.

While many potential tumor markers exist, only a few are reliable enough for routine clinical use.

How Are Tumor Markers Used in Cancer Care?

Tumor markers play a multifaceted role in cancer care, offering valuable information beyond a simple positive or negative result. While not used alone, they complement other diagnostic tools such as imaging (CT, MRI, PET) and biopsies.

One primary use is in prognosis, which is to help predict cancer aggressiveness and guide treatment decisions. A very high marker level at diagnosis may suggest a larger or more advanced tumor, influencing therapy intensity. Sometimes, tumor markers might be integrated into formal staging systems.

Tumor markers are also crucial for monitoring treatment effectiveness. In cancers that produce a known marker, doctors can track its levels over time. A decreasing level typically indicates that treatment is working, while stable or rising levels may suggest resistance, prompting a change in therapy. Marker trends can reflect treatment response earlier than imaging scans, offering a biochemical snapshot of progress.

After successful treatment, regular monitoring can reveal a return of cancer before symptoms arise or imaging shows changes. In this context, the trend of increasing levels is more significant than a single high reading, making tumor markers key tools in long-term cancer surveillance.

Can a Tumor Marker Test Diagnose Cancer?

The short answer is generally no; a tumor marker test alone is not sufficient to diagnose cancer.

While an elevated tumour marker can be a significant red flag that warrants further investigation, it is not definitive proof of cancer. Many non-cancerous factors can influence marker levels, making them an unreliable standalone diagnostic test. The presence of cancer can only be confirmed through a biopsy, where a small sample of tumor tissue is removed and examined under a microscope by a pathologist.

Which Are the Most Commonly Used Markers for Specific Cancers?

A wide list of tumor marker tests exists, with specific tumor markers being particularly useful for certain cancer types. Here is a look at some of the commonly used markers and their clinical context:

• Prostate-Specific Antigen (PSA): PSA is a marker for prostate cancer. It’s not ideal for general screening due to many false positives. It’s useful for monitoring recurrence and advanced disease.
• CA-125: CA-125 is used for ovarian cancer. It can be high in many non-cancer conditions, especially in pre-menopausal women. It helps monitor treatment and detect recurrence.
• Carcinoembryonic Antigen (CEA): CEA monitors colorectal cancer after surgery. It is not good for screening. It can also rise in other cancers and smokers.
• CA 15-3 and CA 27.29: These markers track advanced breast cancer. They don’t help with early detection. Tissue markers like ER, PR, and HER2 guide breast cancer treatment.
• Alpha-fetoprotein (AFP) and Human chorionic gonadotropin (hCG):  both help diagnose and monitor certain testicular and ovarian tumors. AFP itself is also used for liver cancer. They assist with staging and treatment monitoring.
• CA 19-9: This is a marker associated with pancreatic cancer and cancers of the bile duct and gallbladder. It is CA 19-9 is used for pancreatic, bile duct, and gallbladder cancers. It tracks treatment response. It can also rise in non-cancer conditions like pancreatitis.

This is just a partial list, and it highlights how a specific marker used is tied to a specific type of cancer and a specific clinical question.

What Does the Future Hold for Tumour Marker Research?

Tumor marker research is growing quickly, aiming to find more accurate and sensitive markers to improve cancer detection and treatment.

One main goal is to discover new markers or groups of markers that can detect cancer early, when it is easier to treat. This could lead to better screening tests for cancers like ovarian, pancreatic, and lung cancer, which currently lack good screening methods.

A very promising area is circulating tumor DNA (ctDNA), also called a “liquid biopsy.” This test looks for tiny pieces of cancer DNA in the blood. It may be more precise than current protein markers because it examines the tumor’s actual genetic material. Liquid biopsies could help find cancer early, identify mutations to guide personalized treatment, monitor how well treatment is working, track drug resistance, and detect leftover cancer cells after surgery to predict recurrence.

Researchers are also using advanced methods like proteomics and metabolomics to find new tumor markers. Combining several markers with artificial intelligence might give more accurate results than single markers. The goal is to find markers unique to cancer cells and present in higher amounts even at early stages.

Though current tumor markers aren’t perfect, they are valuable tools. Future research promises more precise and powerful ways to detect and treat cancer.

Summary

• Tumor markers (or tumour markers) are substances, often proteins or genetic material, that can be elevated in the presence of cancer. They are found in blood, urine, or the tumor tissue itself.
• They are not used alone to diagnose cancer because levels can be affected by many benign conditions. A biopsy is almost always required for a definitive diagnosis.
• Tumour markers are most useful for determining prognosis, monitoring a patient’s response to cancer treatment, and watching for cancer recurrence after treatment has concluded.
• Different tumor markers are associated with specific cancer types, such as PSA for prostate cancer, CA-125 for ovarian cancer, and CEA for colorectal cancer.
• A tumor marker test result must be interpreted carefully by a doctor, considering the trend over time (not a single value) and combining it with other information like symptoms and imaging scans.
• Research into new tumor markers, like circulating tumor DNA (liquid biopsy) and multi-marker panels, holds great promise for improving the early detection and personalized management of cancer.

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Further References

1. National Cancer Institute. Tumor Markers [Internet]. National Cancer Institute. 2019. Available from: https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
2. National Cancer Institute. Tumor Markers in Common Use – National Cancer Institute [Internet]. www.cancer.gov. 2019. Available from: https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list
3. Alix-Panabières C, Pantel K. Liquid Biopsy: From Discovery to Clinical Application. Cancer Discovery [Internet]. 2021 Apr 1;11(4):858–73. Available from: https://pubmed.ncbi.nlm.nih.gov/33811121/
4. Cancer C. Tumour marker tests [Internet]. Canadian Cancer Society. 2024. Available from: https://cancer.ca/en/treatments/tests-and-procedures/tumour-marker-tests

Disclaimer: This article is for educational purposes only. Please consult your healthcare provider for personalized medical advice.