A scientist prepares samples for DNA analysis. (Photo by Christopher Furlong/Getty Images) Liquid biopsies are a hot topic in medicine. Theoretically, they allow doctors to analyze tumors by picking up minuscule amounts of tumor DNA in the blood, providing an alternative to painful, invasive biopsies. The potential implications of these tests for patients are wide-ranging, with oncologists using them to monitor response to treatment, to see if the tumor is progressing or even to select which patients are eligible for clinical trials for new drugs. Two prostate cancer researchers from The Brady Urological Institute at Johns Hopkins wanted to identify the best liquid biopsy test to recommend to their patients. So they did what any good scientists would do and designed an experiment to find out which of two leading products in the market worked better. Unfortunately, they didn't find themselves choosing between good options, but mildly different ones; they were ultimately left puzzled as to whether either test was actually giving accurate results at all. In the study published yesterday in JAMA Oncology, researchers compared two commercially available tests; the Guardant360 from Guardant Health Inc. and PlasmaSELECT-R64 from Personal Genome Diagnostics, which sequenced parts of 73 and 64 genes, respectively, to pick up errors commonly found in cancers. The researchers sent identical samples from the same blood draw to each company to run through their panels. Remarkably, the results from sections of DNA analyzed by both companies completely matched in only three of 40 patients, raising the rather worrying possibility that patients could be prescribed different treatments based not on the mutations in their tumors, but by which commercial provider their physician uses for the analysis. The lead author of the study, Gonzalo Torga, M.D., has concerns about the tests. "Liquid biopsy is a promising technology, with an exceptional potential to impact our ability to treat patients, but it is a new technology that may need more time and experience to improve," Torga said. "We can’t tell from these studies which laboratory’s panel is better, but we can say that certification for these laboratories must improve." Many biological tests have error margins and acceptable limits for false positives and negatives, but biologically there is no gray area in this case. The mutations that the tests claim to detect are either there or not. Both company laboratories used to analyze the samples are fully licensed and accredited by the relevant regulatory agencies and report a high success rate in identifying mutations, or the absence of them. Given this, there really is little excuse for this lack of concordance between the products from the two companies, especially at a cost of around $4,000 per analysis. The stakes are extremely high for oncologists putting their trust in liquid biopsy tests, and this important study suggests that the technology is simply not ready to help them make critical decisions for patients. Inaccurate detection of DNA mutations could mean that patients are prescribed therapies that are unlikely to help them and, perhaps more seriously, may miss out on experimental therapies that might.
Liquid biopsy technology may not be fully mature enough to deliver reliable results, according to two researchers at Johns Hopkins at Guardant Health . A comparison test to find mutations using Guardant360 by Guardant Health and PlasmaSELECT-R64 from Personal Genome Diagnostics produced results that exactly matched in two out of just three patients. Study lead author Christopher Furlong/Getty Images said the test demonstrated that "certification for these laboratories must improve".