Screening for colorectal cancer via a blood-based test may be as sensitive and specific as stool-based tests, according to the first prospective study to evaluate its accuracy in a screening population. The new blood-based test is reportedly able to detect circulating tumor DNA, which then can be analyzed for various characteristics, including cancer genetics and methylation.
The LUNAR-2 test from Guardant Health was 100% sensitive and 90% specific for detecting CRC in a multicenter Spanish study. At 95% specificity, it was 88% sensitive, said investigator Paloma Peinado, MD, a medical oncologist at HM Hospitales, in Madrid, Spain.
“In this real-world, prospective study of individuals eligible for colonoscopy, the sensitivity and specificity of the multi-modal blood-based test reaches thresholds consistent with available stool-based screening options,” Dr. Peinado said. “The reported performance, combined with a more acceptable mode of testing, suggests that this blood-based test may be a viable CRC screening option that could improve screening adherence.”
Real-World Results In Line With Published Data
This study, the results of which Dr. Peinado presented at the 2022 Digestive Disease Week (abstract 226), was the first prospective, real-world population study evaluating this particular assay. Dr. Peinado added that “it is promising to see that the performance in the screened cohort is consistent with previously reported data in case-cohort studies,” in which the test achieved 91% sensitivity for CRC at 94% specificity (J Clin Oncol 2021;39[15]:3536-3536).
The prospective observational study evaluated 557 individuals who were 45 to 84 years of age and gave blood samples before colonoscopy. One-third of the group enrolled were at average risk for CRC, 49% were symptomatic, 11% had a positive family history of CRC, 6% had a positive stool-based test result and 1% presented for colonoscopy for other reasons.
The primary analysis correlated the results from the LUNAR-2 test with the most advanced colonoscopy finding. The LUNAR-2 test looks for circulating tumor DNA (ctDNA) mutations known to be present in cancer, analyzes which genes are turned on or off throughout the genome, and assesses ctDNA fragment size, which can indicate the presence of cancer. The analysis concludes with a final abnormal or normal test result. The result indicated the presence of CRC (abnormal) or non-advanced adenoma/no cancer (normal).
Accuracy of the Assay
Colonoscopy findings showed CRC in eight patients (1.4%), advanced adenomas in 41 (7.4%) and no advanced adenomas or CRC in 508 (91.2%).
At 90% specificity, the blood-based assay was 100% sensitive, identifying all eight CRCs found on colonoscopy. At 95% specificity, the test was 88% sensitive, identifying seven of the eight cases—missing one case of stage II cancer, Dr. Peinado reported.
“There were no differences in sensitivity or specificity based on the indication for colonoscopy,” she said, “and specificity did not differ when restricting the analysis to only those with a negative colonoscopy.”
In comparison, for stool-based testing, previous studies documented that the multi-target stool DNA test had a sensitivity of 92% and a specificity of 86%, while the fecal immunochemical test was 73% sensitive and 94% specific (N Engl J Med 2014;370[14]:1287-1297). Colonoscopy was reported to be 95% sensitive and 86% specific (JAMA 2021;325[19]:1998-2011).
Data Needed on Detection Of Advanced Adenomas
Dr. Peinado and her co-investigators did not calculate the sensitivity and specificity for advanced adenomas in the study, noting that these will be analyzed in the future, to provide a fuller look at the potential of the test for use in CRC screening.
A study using an updated version of this multimodal test, the ECLIPSE trial (ClinicalTrials.gov Identifier: NCT04136002), did include data on advanced adenomas. Guardant announced positive results from the trial in December. According to a press release from the company, the test demonstrated 83% sensitivity in detecting CRC and 13% sensitivity in detecting advanced adenomas. Specificity was 90% in participants without advanced neoplasia and those who had a negative colonoscopy result. Based on these results, Guardant noted that it planned to complete its premarket approval submission to the FDA in the first quarter of this year.
“There is a lot of enthusiasm for the development of these blood-based colon cancer screening tests because the technology has rapidly improved,” said Aasma Shaukat, MD, MPH, the Robert M. and Mary H. Glickman Professor of medicine and gastroenterology at the NYU Grossman School of Medicine, in New York City. “We used to not be able to detect cancers until they were fairly late. … Now, technology allows us to pick up [ctDNA] and also proteomic and metabolic signatures, where we can start detecting cancer signals earlier and earlier.”
Referring to several blood-based tests now in clinical trials, Dr. Shaukat added, “We’ve seen very promising pilot data.” The ability of these tests to detect advanced adenomas, which has yet to be shown, “will truly determine their [value].”
—Caroline Helwick
Dr. Peinado reported financial relationships with Guardant Health, Lilly and Merck. Dr. Shaukat reported a financial relationship with Freenome.
This article is from the March 2023 print issue.