Jim Poggi
By Jim Poggi
A review of tumor markers
Quick – name a category of lab testing for a serious patient disease state that spans CLIA waived, moderate and high complexity.
For bonus points, name a lab testing category rapidly expanding with advances in molecular testing and new multi-analyte assays with algorithmic analysis (MAAA), the latest category of testing recognized under the Clinical Lab Fee Schedule.
And no fair doing a google search on tumor markers, because that is the answer I’m looking for.
There’s a lot going on in the world of tumor markers, from new recommendations on colorectal cancer (CRC) screening beginning earlier (age 45 instead of 50), to new FIT/DNA tests for colorectal cancer, new molecular markers for a wide variety of cancers and the latest recommendations on prostate cancer screening – from the US Preventative Services Task Force which re-asserts the value of PSA testing in men aged 55 to 69.
Starting point
With all there is to cover, where to start? While we discuss tumor marker tests with customers nearly every day, I think it pays to start with a definition of tumor markers. This one is from the National Cancer Institute: “Tumor markers are substances that are produced by cancer or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. Most tumor markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in cancerous conditions. These substances can be found in the blood, urine, stool, tumor tissue, or other tissues or bodily fluids of some patients with cancer. Most tumor markers are proteins. However, more recently, patterns of gene expression and changes to DNA have also begun to be used as tumor markers.”
All by itself, that definition tells us why current tumor markers lack a key requirement to be excellent diagnostic tools; they lack specificity since both cancerous and non-cancerous cells produce the substances we use as tumor markers today. This is the reason there has been so much debate about the usefulness of PSA in particular. Tumor markers when used for screening purposes today have an incidence of “false positive results” which future tumor markers aim to correct.
The future is coming fast. In addition to improved specificity of some new molecular markers, newer tumor markers hold promise to aid in assessing pre-disposition of patients to cancer, and are already being used to predict which therapeutic choices will be most effective. The range of diagnostic benefits of the newer markers is expanding quickly, as are the number of new tumor markers being brought to market.
Some of the classic tumor markers on the market today are summarized below:
| Tumor Marker | Associated Cancer | CLIA Category | Developments/Clinical Utility |
| FIT | Colorectal Cancer | Waived | New blood based tests and FIT/DNA tests are entering the market |
| PSA/Free PSA | Prostate Cancer | Moderate | Multianalyte assays with algorithmic analysis (MAAA) are entering the market to improve positive predictive value |
| CA 19-9 | Pancreas, GI System Cancer | Moderate | Assess treatment response |
| CA 15-3/CA 27.29 | Breast Cancer | Moderate | Assess treatment response |
| CA-125 | Ovarian Cancer | Moderate | For diagnosis and treatment response |
| AFP | Liver Cancer | Moderate | For diagnosis and treatment response |
Some of the newer tumor markers entering the market are summarized below:
| Tumor Marker | Associated Cancer | CLIA Category | Developments/Clinical utility |
| ALK gene rearrangements and expression | Non Small Cell Lung Cancer | High complexity | Biopsy; used to determine treatment and prognosis |
| BRAF V600 mutations | Colorectal Cancer and Cutaneous Melanoma | High complexity | Match patients to the most effective treatment |
| EGFR gene mutation analysis | Non Small Cell Lung Cancer | High complexity | Help determine treatment and prognosis |
| Estrogen receptor/Progesterone receptor | Breast Cancer | High complexity | Select patients who would benefit from hormone therapy or other alternate therapies |
| BRCA1, BRCA2 | Ovarian Cancer | High Complexity | Assess patients for most appropriate therapy |
| KRAS gene mutation analysis | CRC and Non Small Cell Lung Cancer | High complexity | Assess patients for most appropriate therapy |
| Methylated DNA biomarkers (Septin 9; others in development) | CRC and Other Cancers | High complexity | Help diagnose |
Future impact
You may be thinking “Wow, that’s a lot of science. Does it impact me and my customers? If so, how?”
It’s a big deal, and we are just beginning to see the changes in the tests we will use in the future to diagnose and treat cancer. Most of the newer tests are still too complex or sophisticated to be useful in the physician office, but that is likely to change. In my opinion, there is probably no area of lab testing undergoing more rapid, and more fundamental, change today than in tumor markers.
A lot of the changes have to do with the quality of the tumor marker tests. Historically, tumor markers tended to be developed as “incidental findings” associated with development and progression of cancer. PSA and early fecal occult blood tests for colorectal cancer are excellent examples. Both are often present or elevated in the presence of cancer, but neither are as specific as clinical practitioners need them to be as perfect lab diagnostic tools. But, the changes we are experiencing today with newer tumor marker tests add numerous clinical benefits including greater specificity and accuracy, the opportunity to help tailor treatment methods and the beginnings of understanding the genetic changes brought about by the development and progression of cancer.
Staying informed keeps you sharp as a consultant and helps you maintain your competitive edge. As an important side note, some of the new tumor marker tests are now classified in the category of Multianalyte Assays with Algorithmic Analysis (MAAAs), which are the fastest growing category of Medicare reimbursement for lab tests, because their reimbursement per test is so high, and also because the number of these tests available is growing rapidly and their clinical importance is increasing.
How else can you keep up with the rapid changes in the tumor marker market?
- Discussions with key PC suppliers
- Ask your category team
- Watch this space
- Follow the news (via AACC and other clinical resources)
Stay informed. Tomorrow is here. Be part of it.