COMMON, DEADLY AND LARGELY PREVENTABLE. Digestive diseases researcher Folasade May laid out the need that prompted a session on emerging colorectal cancer screening tests at the American Association for Cancer Research (AACR) Annual Meeting 2024, held in April in San Diego. (The AACR also publishes Cancer Today.)

May, a gastroenterologist at UCLA Health in Los Angeles, pointed out that colorectal cancer is the third most common cancer in men and women and the second most common cause of cancer death in the U.S. Recommendations call for all adults over 45 to be screened, and testing options include inexpensive at-home kits and colonoscopy, which can remove dangerous polyps before they become cancerous. Despite this, she said, 23 million people in the U.S.—one in three eligible adults—have not been tested.

“Are noninvasive tests the solution to this problem?” asked Samir Gupta, a gastroenterologist with UC San Diego Health. He shared results from a survey of unscreened Americans that asked how they would prefer to get colorectal cancer screening. Less than 14% of respondents chose colonoscopy, while more than 34% preferred an existing stool DNA test.

Digestive disease researchers Samir Gupta, Rachel Issaka and Folasade May discuss emerging tests to screen for colorectal cancer at the AACR Annual Meeting 2024 in San Diego on April 8. Photo by Eric Fitzsimmons

Three existing noninvasive tests have different strengths and benefits, according to May. The fecal immunochemical test (FIT), the high-sensitivity fecal occult blood test (FOBT) and a stool DNA test sold under the brand name Cologuard require collecting stool samples, but they can be done at home with little or no preparation. In terms of sensitivity—the ability to detect colorectal cancer—and specificity—the ability to identify if someone does not have colorectal cancer—each of these tests lags behind colonoscopy, the gold standard for colorectal cancer screening. Colonoscopy scores highly on both measures but requires uncomfortable preparations and often involves sedation.

Advances in testing featured at the session could further broaden options for screening and close the gap in screening accuracy with colonoscopy. May discussed two examples of stool-based screening advances that may offer more accurate results than the current generation of tests if early indications bear out.

In one study, 8,920 people over 45, who were at average risk for colorectal cancer and not up to date with screening, were screened with both a multitarget stool RNA test and a FIT. The results, published Nov. 14, 2023, in JAMA, found that the RNA test had 94% sensitivity compared with 78% for FIT.

The second test, the sDNA-FIT 2.0, is an update of the Cologuard fecal DNA test. The updated assay includes a new molecular panel that uses updated DNA biomarkers, May said. Like the current version, it includes a FIT as part of the assay. In results published March 14, 2024, in the New England Journal of Medicine, samples from 20,176 average-risk adults ages 45 and older showed 93.9% sensitivity compared with 67.3% for FIT.

While stool-based tests look to improve on an existing framework for colorectal cancer screening, blood tests may offer an entirely new option. Rachel Issaka, a gastroenterologist at Fred Hutch Cancer Center in Seattle, presented data from the ECLIPSE study, which was also published March 14, 2024, in the New England Journal of Medicine and on which she and Gupta were authors. A blood test using cell-free DNA was found to have 83.1% sensitivity and 89.6% specificity for colorectal cancer or advanced precancerous lesions. Higher-stage cancers were detected more consistently. The test caught 100% of locally advanced or metastatic cases but had 80.6% sensitivity for localized cases and detected less than 14% of advanced precancerous lesions. Issaka noted that this was the first blood test for colorectal cancer that achieved accuracy comparable with the stool-based screenings. She said that the addition of the blood-based option could improve colorectal cancer screening rates.

Gupta pointed out that multiple randomized trials found offering noninvasive tests increased screening adherence. One study found offering a stool-based test alone or offering a choice of the stool-based test or colonoscopy each achieved higher rates of adherence compared with offering colonoscopy alone. But Gupta also identified issues that should be addressed in research, policy and implementation to allow the next generation of tests to make an impact.

Gupta said abnormal tests need to be followed with a colonoscopy, which can prevent cancer by removing precancerous lesions and is necessary for diagnosis. Failing to follow up after a FIT was associated with a 2.5-fold increase in colorectal cancer death, Gupta said. “The public health impact of increased uptake of noninvasive tests is highly dependent on achieving high rates of colonoscopy completion,” he said. “Frankly, an abnormal noninvasive test that’s not followed by colonoscopy is worthless.”

Some of the racial and ethnic populations who have the greatest need in colorectal cancer, such as African American men, are also disproportionately low income and underinsured, according to Gupta. Realizing the potential public health benefits of new screening options will depend on making sure that all groups have access to the tests, along with efforts that encourage screening and make it easy to complete, Gupta said.

“We need policies that promote timely access to new tests, as well as abnormal test follow-up if we are going to really realize the promise of these tests for all populations,” Gupta said.

Eric Fitzsimmons is an editor at Cancer Today.

Editor’s Note: On July 29, 2024, the Food & Drug Administration (FDA) approved the blood-based screening test for colorectal cancer that was the subject of the ECLIPSE study. The test, manufactured by Guardant and sold under the brand name Shield, is the first blood test approved by the FDA as a primary screening option for colorectal cancer.