A new study shows that assessment of microsatellite instability (MSI) using a cell-free DNA (cfDNA) sequencing method — liquid biopsy — had high concordance with tissue-based testing.

According to the study, microsatellite instability (MSI) status can predict responses to immune checkpoint blockade. Guidelines issued by the National Comprehensive Cancer Network recommended MSI testing in at least 9 cancer types (including cervical, cholangiocarcinoma, colorectal, endometrial, esophageal and esophagogastric, gastric, ovarian, pancreatic, and prostate cancers), but testing is often underused, due in part to tissue insufficiency or unavailability.

In order to validate using liquid biopsy results for MSI detection, researchers compared results from 1145 samples tested with the Guardant360 cfDNA platform to MSI status determined using tissue testing taken from medical records.

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The overall accuracy for the liquid biopsy testing was 98.4%, according to researchers. MSI-high status was correctly detected in 87% of samples from 949 unique evaluable patients, and the status of microsatellite stable/MSI-low was accurately detected in 99.5% of samples. The positive predictive value was 95%.

“Furthermore, we demonstrate clinical utility by showing that MSI-H patients as detected by cfDNA benefit from [immune checkpoint blockade] therapy in a manner similar to that reported for tissue-defined populations, expanding the availability of MSI detection to all patients regardless of tissue availability or requirement to undergo invasive tissue acquisition procedures,” the researchers wrote.

The study also looked at clinical outcomes from 16 patients with gastric cancer whom were determined by liquid biopsy to be MSI-high and were subsequently treated with immunotherapy. There was “robust clinical activity” in patients who were MSI-high, according to authors, with 63% achieving partial or complete remission.

The researchers noted that the findings are limited to gastric cancer, but that “the observed objective response rate is consistent with expectations form tissue-based studies, suggesting that [immune checkpoint blockade treatment] based on cfDNA MSI results should achieve expected outcomes across solid tumor types.”

Disclosure: Many of the authors disclosed they were stock owners and/or current or former employees of Guardant Health.


Willis J, Lefterova MI, Artyomenko, et al. Validation of microsatellite instability detection using a comprehensive plasma-based genotyping panel [published online August 4, 2019]. Clin Cancer Research. doi: 10.1158/1078-0432.CCR-19-1324