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The Promise of Tumor Markers

Oncologists hope that tumor markers can be used for true early detection of cancer. Many of today's detection methods use imaging tools that can find a cancer only after it has been present many years, often as much as a decade or two.


Fig 1: Find tumors at the latent phase


Fig 2: The tumor is much smaller if found during the latent phase (0.01- 0.1 cm)


The graphs above indicate the current limit of clinical detection for most tumors. It is estimated that about 70% of the natural growth of a tumor has already taken place by the time it is detected today. Images courtesy of BioMark Technologies

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What are the potential advantages of using tumor markers?

Although tumor markers are usually imperfect as screening tests for detection of occult (hidden) cancers, once a particular tumor has been found using a marker, the marker may be a way of monitoring the success (or failure) of treatment.

The tumor marker level may also reflect the extent (the stage) of the disease, indicating how quickly the cancer is likely to progress and helping to determine the prognosis (outlook).

Rising levels on test results can be, but are not always worrisome. Although changes in tumor marker levels may be cause for alarm, other non-cancerous diseases can cause test results to vary. Conditions in the lab that processes tests may also alter the results.

Patients should always talk to their oncologist about their test results and keep asking questions until they understand how these results will impact their prognosis and treatment plan.


Advantages of using tumor markers include:

Early detection

  • Providing more information about the disease to allow for tailored treatments to be used, resulting in improved efficacy and survival
  • Avoiding side effects from having unnecessary treatments
  • Offering less invasive diagnostics
  • Improving quality of life, and
  • Reducing costs

What are the potential disadvantages of tumor markers?

Being able to deduce diagnostic patterns that are unique to specific cancer states is a challenge because of the biological variability in an individual patients sample, as well as the huge range of biomarker concentrations in all patients compared.

Differences in sample collection, handling or storage, and profiling techniques among various research sites may change the protein profile obtained from a given sample. Therefore, standardization issues regarding biological variation, preanalytical variables and analytical variability must be tackled before standard values can be established.

A major problem in the identification of cancer biomarkers is the very low concentrations of markers obtained from tissues with small, early-stage cancer lesions.


Fortunately, investigators have found a new way to amplify and concentrate these biomarkers in the blood.

The albumin molecule that circulates in our bloodstream acts as a molecular mop, grabbing low-molecular-weight proteins as they are prepared for elimination from the blood.

The "mop" actually helps collect and amplify (more than 100-fold) the lowabundance serum protein patterns needed for analysis.


Image courtesy of the National Cancer Institute


Other Problems Include:

  • Lack of reliability
  • Proteins and/or modified proteins may vary among individuals, between cell types, and even within the same cell under different stimuli or different disease-states. So it is difficult to know which value obtained from an individual is accurate and what value in different patients indicates a problem.
  • Normal cells as well as cancer cells can produce most tumor markers.
  • Tumor markers are not always present in early-stage cancers.
  • Tumor markers can be present because of noncancerous conditions.
  • People with cancer may never have elevated tumor markers in their blood.
  • Even when tumor marker levels are high, they are not specific enough to confirm the presence of cancer.


The following comments are excerpts from the case study:

PSA Testing: Yes, No, Maybe?
Recent Research, Guideline Updates Add to Controversy
By Gina Rollins

"PSA is found in normal prostate tissue and at elevated levels when the gland is inflamed. Since PSA is not specific to prostate malignancy, a diagnosis of prostate cancer based on rising PSA serum levels results in a high rate of false positives-up to 75% according to some studies. False positive values are highly undesirable because they trigger costly, invasive medical interventions that divert healthcare resources that could be better spent.

Biopsies of 100 suspected prostate cancer patients with PSA readings of 3 ng/mL or higher will yield only 25 confirmed cases. In addition, 40% of PSA-negative readings are false negative. The FDA approved PSA testing at a time when prostate cancer diagnostics were essentially nonexistent. Were the PSA test to come up for regulatory review today, it is unlikely it would be approved for use in prostate cancer screening.

Diagnostic tests that are approved for a single purpose are often used in situations for which the test was not designed. The PSA test is a prime example. PSA was originally approved in 1985 as a test to detect the recurrence of prostate cancer in men who had been previously treated for the disease with radiation or surgery.

Today the test is routinely prescribed as a screening tool despite the fact that evidence linking PSA testing to improved outcomes is lacking."




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