The optimal treatment of solid tumor patients requires good cancer treatments as well as biological tests or markers that can indicate when these treatments should be utilized. An example of such indicators are the specific proteins that various tumors produce and secrete into the bloodstream. These include carcinoembryonic antigen (CEA), associated with colorectal cancer as well as other epithelial malignancies; prostate-specific antigen (PSA), associated with prostate cancer; CA125, associated with ovarian cancer; CA19-9, associated with pancreatic cancer and other cancers of the biliary tract; alpha-fetoprotein (AFP), associated with liver cancer; and others. They are of great help in confirming and establishing the diagnosis of the site of the malignancy at the time of presentation.
Even more importantly, these serum markers are useful in monitoring the progress of treatment for the various cancers. The response to treatment can be assessed by increases or decreases in the level of the tumor marker for a patient with advanced disease. For a patient who has had their tumor resected and is considered to be disease-free, the tumor marker can be the primary and best tool for ongoing surveillance and monitoring to detect recurrence of the tumor and to precipitate further diagnostic and therapeutic maneuvers.
The truth is that these serum protein biomarkers vary in quality and often lack the precision, i.e., the sensitivity and specificity, that one would desire for the purposes cited above. Thus, it is frequently the case that recurrent disease is present when the tumor marker is normal and therefore it gives the patient and the oncologist false reassurance. Thus, a new technology has developed that has significantly greater sensitivity and specificity for the presence of disease and, therefore, provides a more accurate picture of the status of the cancer patient. This test, ctDNA or circulating tumor DNA, came into increasing use about two years ago and is becoming more and more the norm and a standard test in the assessment and monitoring of certain tumors, most notably colorectal cancer, and increasingly breast cancer and lung cancer.
The ctDNA test is a non-invasive blood-based biomarker that reflects cancer-related abnormalities found in tumor tissue. Multiple studies indicate that it is a sensitive and specific assay for the detection of molecular residual disease. It detects the presence of tumor DNA that is present in the blood and reflects the breakdown of dead tumor cells. The presence of this tumor DNA may precede the presence of visible radiologic abnormalities by months, but the fact that the test is positive has a predictive value close to 100% that such radiologic tumor abnormalities will eventually appear. Thus, a positive ctDNA test is an ominous sign for the patient and highly predictive of recurrence.
For those who have a negative ctDNA test following a curative resection, there is a decreased risk of recurrence, though there is no absolute guarantee that recurrence will not occur; there is a small false negative rate (a few percent). As stated above, the ctDNA test performs better in this regard than the serum CEA (for colorectal cancer).
What can one do for the patient who has a positive ctDNA test? If the patient has not yet received adjuvant systemic chemotherapy, that is an option, and frequently the ctDNA will revert to negative after a course of such therapy. Presumably this will ameliorate the negative outcome associated with the positive ctDNA test. Otherwise, a patient with a positive ctDNA test has good reason to be anxious.
For patients with breast cancer, those who test positive after surgery should be considered high-risk and be treated accordingly; while conversely, those who are negative can be considered low-risk and may be treated with less aggressive interventions, or even be simply observed and monitored.
Likewise, ctDNA testing has been shown to be prognostic in patients with lung cancer who have undergone curative resection. Its use is currently being assessed for bladder cancer, multiple myeloma and other cancers. There is little doubt that this is a technology that is rapidly going to overtake the discipline of oncology with various applications. Probably its most profound effect will be to reduce the settings in which chemotherapy will be utilized by identifying patients at low risk for recurrence.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
