ECLIPSE: Blood-Based Test Shows 83% Accuracy for Detecting Colorectal Cancer

William Grady, MD

Credit: Fred Hutchinson Cancer Center

As the third most diagnosed cancer and the second leading cause of cancer-related death in the US, early detection of colorectal cancer is of paramount importance, yet many individuals eligible to get screened do not adhere to screening guidelines.¹

A cell-free DNA (cfDNA) blood-based assay may offer a more appealing alternative for patients and improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. Indeed, findings from the Evaluation of the ctDNA LUNAR Test in an Average Patient Screening Episode (ECLIPSE) study demonstrated 83% sensitivity for colorectal cancer, similar to the accuracy of current stool tests but less than that of a colonoscopy.¹

“Colorectal cancer is common and very preventable with screening, but only about 50% to 60% of people who are eligible for screening actually take those tests,” William Grady, MD, medical director of the Gastrointestinal Cancer Prevention Program at Fred Hutchinson Cancer Center, said in a press release.² “Getting people to be screened for cancer works best when we offer them screening options and then let them choose what works best for them.”

In 2021, the US Preventive Services Task Force updated its colorectal cancer screening recommendation to include all adults 45 - 75 years of age, expanding upon the previous recommendation in adults 50 - 75 years of age.³ Although several screening tests can be used to find polyps or colorectal cancer, a positive or abnormal result on certain screening tests requires a colonoscopy, the gold standard for colorectal cancer detection and prevention. However, many people eligible for screening do not get screened, highlighting the need for an easily administrable test that patients are more likely to adhere to.⁴

A prospective, observational, multicenter study conducted across 265 sites in the US, ECLIPSE was designed to evaluate the performance of Guardant Health’s Shield, a cfDNA blood-based test, for detecting asymptomatic and early-stage colorectal cancer in a screening-relevant population. For inclusion, patients were required to be 45 - 84 years of age at the time of consent, at average risk for colorectal cancer, and undergoing routine screening with colonoscopy. Key exclusion criteria were a history of cancer, a known diagnosis of inflammatory bowel disease, a hereditary predisposition to colorectal cancer, a history of colorectal cancer in a first-degree relative, and recent receipt of screening for colorectal cancer.¹

The study’s coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions, defined as advanced adenoma (tubular adenoma ≥10 mm in the largest dimension, adenoma of any size with villous features, high-grade dysplasia, or carcinoma in situ) or sessile serrated lesions ≥ 10 mm in the largest dimension.¹

A total of 22,877 participants were enrolled in the study, including 65 evaluable participants with colonoscopy-identified colorectal cancer. Investigators randomly selected 10,193 participants without colorectal cancer from the enrolled participants, forming a clinical validation cohort of 10,258 participants.¹

A total of 7861 participants met all inclusion and exclusion criteria, had complete and valid colonoscopy results, had valid cfDNA blood-based test results, and were thus evaluable for final analysis. Among this cohort, the mean age was 60 (range, 45 - 84) years and 53.7% of patients were female.¹

Among those with colorectal cancer detected by colonoscopy (n = 65), 83.1% (n = 54) had a positive cfDNA test and 16.9% had a negative test, indicating an 83.1% sensitivity of the cfDNA test for detecting colorectal cancer (95% CI, 72.2-90.3). Investigators noted the sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3-94.1), but the sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3-15.3).¹

A total of 89.6% of participants without any advanced colorectal neoplasia identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, indicating an 89.6% specificity for any advanced neoplasia (95% CI, 88.8-90.3). Of note, the lower boundaries of the 95% CIs for sensitivity for colorectal cancer and specificity for advanced neoplasia met the prespecified acceptance criteria as established in other FDA-approved screening tests for colorectal cancer.¹

Among 1116 participants with advanced precancerous lesions identified as the most advanced lesion on colonoscopy, the cfDNA blood-based test was positive for 147 (13.2%), equating to a sensitivity of 13.2% (95% CI, 11.3 to 15.3).¹

“The results of the study are a promising step toward developing more convenient tools to detect colorectal cancer early while it is more easily treated,” Grady said.² “The test, which has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer, could offer an alternative for patients who may otherwise decline current screening options."

References:

1. ^{Chung DC, Gray DM, Singh H, et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Eng J Med. doi:10.1056/NEJMoa2304714.}
2. ^{Fred Hutchinson Cancer Center. Clinical study of a blood test shows 83% accuracy for detecting colorectal cancer. EurekAlert! March 13, 2024. Accessed March 13, 2024. https://www.eurekalert.org/news-releases/1037242}
3. ^{US Preventive Services Task Force. Colorectal Cancer: Screening. Recommendation Topics. May 18, 2021. Accessed March 13, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening}
4. ^{US Centers for Disease Control and Prevention. Colorectal Cancer Screening Tests. Colorectal (Colon) Cancer. February 23, 2023. Accessed March 13, 2024. https://www.cdc.gov/cancer/colorectal/basic_info/screening/tests.htm}