The latest issue of the New England Journal of Medicine featured a duet of expansive studies from Guardant Health and Exact Sciences, examining their upcoming tests that aim to increase screening rates and catch earlier cases of colorectal cancer.
Guardant’s liquid biopsy approach put forward data taken from more than 7,800 adults between the ages of 45 and 84, carrying an average risk for cancer—in an analysis from an overarching study of more than 20,000 participants that the company described as one of the largest of its kind, comparing the noninvasive method to regularly scheduled colonoscopies.
The Shield blood test seeks out cancer signals taken from tumor DNA found floating in the bloodstream. The study demonstrated an 83.1% sensitivity for detecting colorectal cancer, with 16.9% of people who had cases discovered during a colonoscopy receiving a false-negative result.
In a statement, Guardant said the findings were “on par with the performance of other guideline-recommended non-invasive screening modalities, where overall sensitivity in detecting colorectal cancer ranges from 74% to 92%.”
The Shield test, which was first unveiled in May 2022, also showed 65% sensitivity in detecting the earliest stage of cancer in pathology-confirmed cases, and 55% sensitivity when relying on clinical findings. Later phases of the disease—including stages II and III, and metastatic stage IV cancer—were all detected 100% of the time.
“Over 50 million eligible Americans do not get recommended screenings for colorectal cancer, partly because current screening methods are inconvenient or unpleasant,” said Guardant co-CEO AmirAli Talasaz. “We are confident that offering an accurate blood test has the potential to significantly reduce preventable colorectal cancer deaths.”
Guardant completed its submission to the FDA for approval in March of last year but has been expecting an advisory committee meeting to supplement the agency’s review; that meeting has not yet been placed on the FDA’s official calendar.
The company said last December it expects to launch the Shield test as an approved in vitro diagnostic in 2024. After first rolling it out as a lab-developed test in 2022, Guardant said the liquid biopsy has since been used by more than 20,000 people.
Exact Sciences, meanwhile, tested out the next generation of its mainstay Cologuard at-home screener. Cologuard Plus showed it could outperform commonly used fecal immunochemical tests, in a head-to-head trial of 20,000 participants who also underwent a colonoscopy.
The company said it submitted its application to the FDA last December—including the results from the latest study, dubbed BLUE-C—and plans to make Cologuard Plus commercially available in 2025, pending the agency’s green light.
“BLUE-C’s publication in The New England Journal of Medicine reflects a decade of deep scientific and medical research in collaboration with Mayo Clinic,” Exact Sciences CEO Kevin Conroy said in a statement. “We’re eager to bring an improved, noninvasive colorectal cancer screening test to patients in Cologuard Plus, as colorectal cancer remains the most preventable, yet least prevented cancer.”
Cologuard Plus met all the study’s endpoints, showing a 94% sensitivity for detecting colorectal cancer as well as 96% specificity among adults ages 45 to 54. According to the company, the test’s low rate of false positives will help reduce the number of avoidable follow-up colonoscopies.
Exact Sciences pegged the test’s sensitivity for detecting early, stage I disease at 87%, compared to a FIT average of 50%. That number rose to 94% for stage II, 97% for stage III, and 100% for stage IV and cases that could not be classified.
The company also claimed that the study’s results could help set the stage for expanding the eligible screening population. While the National Comprehensive Cancer Network lowered its recommended screening age to 45 down from 50 in 2021 (PDF), Exact Sciences said including those average-risk between the ages of 40 and 44 would add 22 million more people in the U.S. That could translate to a $6 billion increase in the colorectal cancer screening market, the company said (PDF).
“Although multiple tests have been developed over time and vary in cost-effectiveness for colorectal cancer screening, the best screening test is the one that gets completed by the patient,” John Carethers, M.D., the University of California San Diego’s vice chancellor for health sciences, wrote in an accompanying NEJM editorial.
Carethers pointed to the overall prevalence of colorectal cancer screening—including noninvasive and endoscopic methods—topping out at about 69% in the U.S. before the COVID-19 pandemic.
To reach a national goal of 80% or more, he suggested encouraging the use of existing approved tests while also improving upon the currently available options.
“Most of the recommended tests, including the two newer tests assessed in the studies now published in the Journal, improve on the sensitivity and approach the specificity of FIT, such that these tests appear to be at least as effective as FIT,” Carethers wrote. “Adherence to screening is a key factor, and ease of test use may contribute to increased adherence.”