Liquid biopsies have been the focus of intense research and, a group of experts impaneled by the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) reported in March, “studies of multiple cancer types indicate that ctDNA analysis can identify the emergence of resistant mutations months earlier than standard radiologic studies, creating an opportunity to test whether changing therapy before clinical progression could improve outcomes.”3

Advances in genomic analysis have aided the progress of the blood tests, but several factors pose challenges.

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“Available evidence indicates that patients with early-stage cancers can harbor less than one mutant template molecule per milliliter of plasma,” the CancerSEEK paper’s authors stated, “which is often beyond the limit of detection of previously reported technologies that assess multiple mutations simultaneously. Yet another issue with liquid biopsies is the identification of the underlying tissue of origin. Because the same gene mutations drive multiple tumor types, liquid biopsies based on genomic analysis alone generally cannot identify the anatomical location of the primary tumor.”

Therefore, while ASCO/CAP panel recognized the promising results of research thus far, they cautioned that blood tests based on ctDNA require much more extensive and broad-based clinical trials before they can be used in routine practice.

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“There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection,” the authors said. “There is no evidence of clinical validity or clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial.”

However, as the National Cancer Institute said in an article on its website last November, “There has been a recent surge of research related to liquid biopsy tests that analyze tumor DNA in blood, called circulating tumor DNA (ctDNA), and several ctDNA-based liquid biopsy tests are in clinical development.”4

In fact, the U.S. Food and Drug Administration (FDA) gave approval to a blood-based cancer test for the first time just 2 years ago. The cobas EGFR Mutation Test v2 can detect epidermal growth factor receptor (EGFR) gene mutations in patients with non-small-cell lung cancer and help identify those who “may benefit from treatment with [erlotinib].”5

However, the FDA advised, “if such mutations are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present.”

“Approvals of liquid biopsy tests make it possible to deliver highly individualized health care for patients,” Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health in Silver Spring, Maryland, explained at the time. “Liquid biopsies also have the potential to allow physicians to identify patients whose tumors have specific mutations in the least invasive way possible.”

The accelerated pace of research is bringing new evidence supporting the use of liquid biopsies in a variety of ways and quickly addressing some of the concerns. As one of the members of the ASCO/CAP panel, Alexander Lazar, MD, PhD, FCAP, of the departments of pathology and genomic medicine at the University of Texas MD Anderson Cancer Center in Houston, said via email, “The field of liquid biopsies is moving very rapidly. Our comments in the manuscript were based on the literature at the time we discussed and wrote the review — almost a year ago. Because of the excitement and work of many in this field, there is more published literature supporting the use of this approach. Using liquid biopsies results to determine therapy for a positive result is clinically feasible; if a mutation is present, acting upon it is reasonable. There is less certainty regarding clinical action on negative results, that is, not seeing a particular mutation. … However,” he continued, “with each study published we are learning how to better apply these tests effectively.”


  1. Heitzer E, Perakis S, Geigl JB, Speicher MR. The potential of liquid biopsies for the early detection of cancer. NPJ Precis Oncol. 2017;1:36. doi: 10.1038/s41698-017-0039-5
  2. Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018; 359:926-930. doi: 10.1126/science.aar3247
  3. Merker JD, Oxnard, GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review {Published online March 5, 2018]. Arch Pathol Lab Med. doi:  10.5858/arpa.2018-0901-SA
  4. National Cancer Institute. Liquid Biopsy: Using DNA in Blood to Detect, Track, and Treat Cancer. Published November 8, 2017. Accessed June 19, 2018.
  5. Food and Drug Administration. FDA News Release, FDA approves first blood test to detect gene mutation associated with non-small cell lung cancer. Published June 1, 2016. Accessed June 19, 2018.