Traditional cancer biomarkers such as PSA, CEA, CA125, CA19-9 etc. have been used for years for aiding in the diagnosis and for monitoring therapy of cancer patients. In general, the diagnostic value of these tests is rather limited due to suboptimal sensitivity and specificity. Thus, none of these tests is recommended for population screening to identify early, and potentially curable, disease. A possible exception is PSA for which its screening application for prostate cancer is still controversial.
More recently, it has been postulated that circulating tumor DNA may be the ultimate cancer biomarker. Circulating tumor DNA represents small fragments of DNA that are released into the circulation. In cancer, this DNA may contain mutations which, if identified early, could be valuable for disease diagnosis. It has also been shown that circulating tumor DNA has prognostic value in patients who have been treated and it may also have predictive value for selection of therapy. We have tremendous interest on circulating tumor DNA because it has the potential to revolutionize cancer diagnostics. However, over-optimism is not recommended, for the following reasons:
- It is technically highly difficult to identify tumor DNA in the circulation because the vast amount of circulating DNA is coming from normal cells. Thus, an assay with exquisite sensitivity is required.
- These assays are highly expensive, about 100x more expensive than traditional cancer biomarkers.
- While there is solid data that this liquid biopsy has prognostic and monitoring value, its capability for early cancer detection is highly questionable. Calculations that we made, based on the amount of total circulating DNA and the fraction of DNA that could come from 1mm tumors, reveal that a small amount of blood (such as 10mL) may not contain a single copy of the cancer genome, thus making the diagnosis impossible.
Clinical trials are now underway to examine if there are cancer-specific mutations in the circulation that can be used for early cancer diagnosis and what is the specificity of these tests. We need to await for this data to be published, before we draw any conclusion about the use of circulating tumor DNA for early cancer diagnosis.