Caution Urged When Using Liquid Biopsies in the Clinic

John Schieszer

A new joint review from ASCO and CAP found insufficient evidence of clinical validity and utility for the use of most ctDNA assays in advanced cancer.

Circulating tumor DNA (ctDNA) assays still lack evidence to support their use in routine cancer care, according to a report from panel of experts. A new joint review from the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) has found that there is insufficient evidence of clinical validity and utility for use of the majority of ctDNA assays in patients with advanced cancer.

“We found that this exciting field is in an early state and much more work needs to be done to develop universal standards for its activation,” said co-chair of the expert panel Alexander Lazar, MD, PhD. Lazar is a professor in the Departments of Pathology and Genomic Medicine, Division of Pathology/Lab Medicine, the University of Texas MD Anderson Cancer Center, Dallas, Texas.

The ASCO/CAP multidisciplinary Expert Panel examined evidence from 77 relevant articles published from January 2007 to March 2017. The review was limited to the analysis of sequence and gene copy number variants in ctDNA from solid tumors.  

The panel found there was not enough evidence to support the use of the majority of ctDNA tests in advanced cancer. In addition, they found insufficient evidence to support the routine use of ctDNA tests for early-stage cancer, making treatment decisions, monitoring how well a treatment is working, finding remaining cancer cells, or for cancer screening.

“The ability to genotype tumors from blood samples is going to be transformational for oncology and pathology. However, we are in early days. The technology of what we can measure exceeds our current ability to understand its clinical impact,” Dr. Lazar told Cancer Network

He said the positive predictive value of these tests is excellent. However, the negative predictive value seems to be suboptimal in many settings. The researchers concluded that there is no evidence of clinical validity and clinical utility to suggest that ctDNA assays are useful for cancer screening, except in a clinical trial.

To date, only a single liquid biopsy test has shown what is considered sufficient clinical utility to be approved by the United States Food and Drug Administration. It is the COBAS assay for mutations in epidermal growth factor receptor, to be used in non–small-cell lung cancer. There is controversy now because currently there are a variety of liquid biopsy tests available for use in clinical practice.

“I’m concerned that, as a medical community, we may rush into routine clinical deployment before we properly understand the strengths, weaknesses, and appropriate context, and thereby prevent ourselves from appropriately recognizing how, where, and when to use liquid biopsies,” Neal Lindeman, MD, an associate professor of pathology at Harvard Medical School in Boston, Massachusetts, told Cancer Network.