The U.S. Preventive Services Task Force (USPSTF) appears on the verge of expanding colorectal cancer screening to individuals ages 45 to 49, based on its latest draft recommendations. If it does, Exact Sciences Corp. is ready. A study in Cancer Prevention Research demonstrated that the Madison, Wis.-based company's Cologuard multitarget stool DNA test had better than 95% specificity in individuals with nonadvanced precancerous lesions or negative findings on colonoscopy.

The prospective study provides additional support to the USPSTF’s planned update to its 2016 recommendations. It moves the start date for screening five years earlier as a grade B recommendation and specifically cites the greater life-years associated with tests like Cologuard, which combine stool DNA analysis with a fecal immunochemical test, compared with other nonvisual assessments. Cologuard is the only U.S. FDA-approved stool test and is administered at home.

"Cologuard may appeal to this younger screening population because they can collect sample at home, without missing work or undergoing bowel prep and anesthesia, and only those patients with a positive Cologuard will require a diagnostic colonoscopy," said Exact Sciences CEO Kevin Conroy.

Increasing colorectal cancer (CRC) screening across the board remains a high priority for public health. CRC trails only lung cancer as a leading cause of cancer deaths in the U.S. In large part, the high number of deaths occur because most people with CRC do not receive a diagnosis until the malignancy has spread.

While screening can prevent CRC, nearly 25 million Americans in the existing recommended screening age range of 50 to 75 have skipped screening. That breaks down to about 20% of those older than 65 and more than one-third of those 50 to 65. Another 19 million people aged 45 to 49 also have not been screened.

The USPSTF recommends that clinicians offer CRC screening selectively to patients between the ages of 76 and 85, citing the risks vs. benefits of undergoing screening, particularly as the cancer is typically slow-growing.

CRC most commonly affects the elderly, but the incidence in younger Americans has increased sharply in the last two decades, with more than 130,000 cases diagnosed between 2004 and 2015. More than half of these cases in younger patients were diagnosed at stage 3 or 4, which is associated with lower survival rates.

Once-a-decade colonoscopy remains the most common type of screening for individuals with average risk of CRC in the U.S. More frequent colonoscopy, which allows direct visualization of the colon and same-procedure removal of polyps or precancerous growths, is recommended for people at higher risk as a result of a family history of CRC, with inflammatory bowel disorders, or whose previous tests detected polyps.

But many people take a pass on CRC screening because the preparation, which requires total cleansing of the bowel, is unpleasant and time-consuming, and can cause persistent adverse effects for individuals with existing bowel diseases and the elderly. Patients also must undergo anesthesia and require transportation home from the screening facility.

As people age, the risk of intestinal perforation, the most serious risk associated with colonoscopy, increases. Notably, when rating the various screening methods, the USPSTF lists the primary risk as “harms from screening with [test] arise from colonoscopy to follow up abnormal [test] results.”

Study results

The Cologuard study “is among the first to evaluate the use of a colorectal cancer screening method in patients between the ages of 45 and 49,” said Paul Limburg, chief medical officer for screening at Exact Sciences.

Of the 983 enrolled participants, the study evaluated 816 who completed a Cologuard test followed within 60 days by a colonoscopy at 31 sites across the U.S. between November 2018 and June 2019. Cologuard bowel samples were collected by patients prior to any preparation for their colonoscopy. Clinicians conducting the colonoscopies were blinded to the results of the Cologuard tests.

None of the patients had colorectal cancer. Advanced precancerous lesions were detected in 48, and 253 had nonadvanced adenomas. Negative colonoscopies occurred in 514 cases. Cologuard demonstrated 95.2% specificity among those with nonadvanced precancerous lesions or negative findings at colonoscopy and 96.3% specificity in the subgroup that included only those with negative colonoscopy findings. There was no difference in specificity by sex.

The researchers noted that Cologuard’s “high specificity would help minimize risk from unnecessary diagnostic procedures in this age group.”

Sensitivity for advanced precancerous lesions was 32.7%, with most of the lesions measuring 10 to 19 mm and none displaying high-grade dysplasia.

"The American Cancer Society guidelines and the 2020 draft [USPSTF] guidelines now say that screening should begin at 45, and these data support the use of Cologuard as a first-line screening option," Limburg added.