Exact Sciences Scores Big as USPSTF Lowers Colorectal Cancer Screening Start Age to 45

Wouldn’t it be great if a government health task force recommended that people use the kind of test you create every year? Something like that just happened to Exact Sciences, maker of the Cologuard home-based colorectal cancer screening test. It happened when the U.S. Preventive Services Task Force (USPSTF) changed its guidelines by recommending that screening for colon and rectal cancer start at age 45, rather than 50. In addition to saving thousands of lives by promoting earlier colorectal cancer detection, the USPSTF announcement is very good news for molecular screening test companies, especially but not exclusively Exact Sciences. Here is a breakdown of the new USPSTF recommendations and their potential impact on screening patterns and the molecular testing market.

The Diagnostic Challenge Colorectal cancer is the third leading cause of cancer death among adults in the U.S., with more than 52,000 people projected to die from the disease in 2021. Most colorectal cancer cases are diagnosed in people ages 65 to 74. Only 10.5 percent of new cases occur in those below age 50. However, the case incident rate among this group has steadily increased—at a nearly 15 percent clip between 2000 and 2016. Unfortunately, there has been no commensurate increase in colorectal cancer screening over this period. According to the USPSTF, in 2016, 26 percent of eligible U.S. adults had never undergone colorectal cancer screening; in 2018, 31 percent adults were not up to date with their screening. The New Colorectal Screening Recommendations The USPSTF reviews its screening recommendations every four years. The new recommendations, which were published in the Journal of the American Medical Association on May 18, are an update to its previous 2016 guidelines and a final version of draft recommendations published in October 2020. The latest revisions are based on a systematic review evaluating the benefits and harms of screening for colorectal cancer in adults 40 or older. The review also examined whether these findings varied by age, sex, or race/ethnicity. As it did in 2016, the USPSTF commissioned a report from the Cancer Intervention and Surveillance Modeling Network Colorectal Cancer Working Group to provide information from comparative modeling on how estimated life-years gained, colorectal cancer cases averted, and colorectal cancer deaths averted vary by different starting and stopping ages for various screening strategies The headline of the new guidelines is the recommendation that asymptomatic adults at average risk start colorectal cancer screening at age 45, rather than waiting until age 50 as the 2016 guidelines recommended. The new recommendation is in line with the American Cancer Society, which also recommended starting routine colorectal cancer screening at age 45 in 2018. According to the USPSTF, adults ages 45 to 75 should undergo routine colorectal cancer screenings. It estimates that earlier screenings would be associated with up to an additional 27 life-years, two to three fewer colorectal cancer cases, and between 0.9 and 1 fewer deaths from the disease, compared to adults who begin screenings at age 50. The task force assigns members of this age 45 to 49 group a “B” grade, as opposed to the “A” grade given to the age 50 to 75 members of the cohort. Even so, a B grade is enough to ensure members who have commercial insurance will not have to pay out-of-pocket costs to receive their screenings under Affordable Care Act rules. First-dollar health insurance coverage for adults starting at age 45 could impact up to 15 million adults, according to the patient advocacy organization Colorectal Cancer Alliance. Meanwhile, the USPSTF recommends that screening in adults ages 76 to 85 be offered selectively as determined by clinicians on the basis of the specific circumstances of the case, including the patient’s overall health, screening history and preferences. Evidence indicates that the net benefit of screening all persons in this age group is small. The task force assigns this group a “C” grade. USPSTF Colorectal Cancer Screening Recommendations

Ages	Recommendations	Grade
50 to 75	Screening for all members	A
45 to 49	Screening for all members	B
76 to 85	Screening for selective cases determined by clinician based on patient’s health, screening history and preferences	C

Impact on the Laboratory Industry Reducing the starting age for colorectal cancer screening to age 45 with a “B” classification will significantly boost sales of molecular screening tests. The real breakthrough came in 2016, when the USPSTF first added molecular colorectal cancer screening to its guidelines. In addition to Multitargeted stool DNA (mtDNA) tests like Cologuard, the task force recommends two other stool-based tests, namely high-sensitivity Guaiac-based fecal occult blood tests (gFOBT) and Fecal immunochemical tests (FIT), as well as direct visualization approaches like colonoscopy. Stool-Based Tests

Test Type	Recommended Frequency
High-sensitivity gFOBT	Every year
FIT	Every year
mtDNA	Every 1 to 3 years based on manufacturer’s recommendations

Direct Visualization Tests

Test Type	Recommended Frequency
Colonoscopy	Every 10 years
CT colonography	Every 5 years
Flexible sigmoidoscopy	Every 5 years
Flexible sigmoidoscopy with FIT	Every 10 years + FIT every year

While there is plenty of competition, Exact Sciences is the clear market leader in mtDNA at-home colorectal testing with the greatest visibility among the late-40 somethings who will now be able to get screened for free each year, especially if it means avoiding colonoscopy. The draft version of the guidelines said that screening with Cologuard every year “would result in more colonoscopies than annual screening with FIT.” But USPSTF softened its position in the final text by adding new language stating that Cologuard “every 1 to 3 years is estimated to provide a reasonable balance of life years gained per estimated follow-up colonoscopy compared with no screening.”