DAY 3: The Landscape of Colorectal Cancer (CRC) Screening

Dr. Shaukat noted that only 59% of adults age 45 years and older are up to date on CRC screening, and rates are even lower at federally qualified health centers (FQHCs). The goal is to reach 80% in every community. The stakes are high because CRC is now the leading cause of cancer death in people under 50 years of age. The established screening options are colonoscopy, the fecal immunochemical test (FIT), and multitarget stool DNA (mt-sDNA) testing. Colonoscopy has the best sensitivity for both CRC and advanced adenomas, but it is invasive. An abnormal FIT or mt-sDNA result must be followed by colonoscopy, so in Dr. Shaukat's words, “all roads lead to colonoscopy.” When choosing among tests, adherence matters most, because the best test is the one that gets done. 

Today's high-resolution colonoscopy procedure is efficient, with good patient and provider experience. Public advocacy, including high-profile campaigns by figures such as Katie Couric, has helped make colonoscopy more widely used. CRC rates in the US have fallen for both men and women since 1975, which shows that screening works. Unfortunately, the large randomized NordICC trial in 2022 found that only 42% of people invited to colonoscopy chose to have one, and the invitation reduced CRC incidence by only 18%, with no difference in CRC mortality between the invited and uninvited groups. This year, the 13-year follow-up from the same group showed a similar lack of effect on mortality and a 19% reduction in CRC incidence that was significant only in men. Dr. Shaukat had the opportunity to write an accompanying editorial stressing the importance of adherence and colonoscopy quality, and noting that the trial was underpowered for mortality. It also placed the findings in the context of other data, with the message that clinicians should not let patients be discouraged or dissuaded, because screening colonoscopy remains the most effective modality.

To address low adherence, four new noninvasive CRC screening tests have received FDA approval. Cologuard Plus was evaluated in the BLUE-C study of 20,176 patients and showed 93.9% sensitivity and 92.7% specificity for CRC, with a very low false-positive rate. Its sensitivity for advanced adenomas is unchanged from the previous Cologuard test, and about 1 in 7 tests is positive and requires follow-up. 

The ColoSense multitarget stool RNA test was studied in the CRC-PREVENT trial, which enrolled 8920 participants, including 36 with CRC and 600 with advanced adenomas. It had 94% sensitivity and 87.9% specificity for CRC, similar advanced adenoma detection as the Cologuard Plus, and a higher positivity rate of 17%. Its performance meets and exceeds the threshold for CMS coverage.

Dr. Shaukat noted that FIT mainly detects advanced cancers, so a test that detects cancer across all stages is needed, and two blood-based tests have now been approved. Shield, a cell-free DNA test, was studied in 22,877 people at 26 US sites, with blood drawn within 60 days before a screening colonoscopy. It showed 83% sensitivity and 89% specificity for CRC, but only 13.2% sensitivity for advanced adenomas, which Dr. Shaukat called no better than chance. This result gave the field some pause. The test performs better for stage II to IV cancers than for stage I disease.

Freenome’s SimpleScreen was studied in 48,995 people at 291 US sites and showed 80% sensitivity and 91.5% specificity. Like the Shield test, advanced adenoma sensitivity was low at 12.5%, and it was better at detecting stage 2 to 4 disease. SimpleScreen was approved a few months ago and now sits within Abbott’s portfolio alongside Cologuard Plus. Data on a second version of the SimpleScreen test, which is designed to improve advanced adenoma detection, were also presented at ACG.

The American Cancer Society has updated its CRC screening guidelines to include blood-based tests, but only for patients who decline stool-based testing or colonoscopy. Media coverage of the new blood tests has led patients to ask for them, however. Dr. Shaukat sees this as an opportunity for education, but said guardrails are needed to reduce confusion. Much of the burden falls on primary care physicians to make sure patients understand the tests’ limitations. The CRC screening menu has become complicated very quickly, and gastroenterologists need to understand it well enough to help guide health systems. A 2024 modeling analysis by Dr. Shaukat and colleagues in Gastroenterology found that a blood test is better than no screening but is not better than colonoscopy and should not be offered first line.

Follow-up remains a major gap. Only 50% to 55% of patients with an abnormal noninvasive test go on to have a colonoscopy, even though they have a 10-fold higher risk of neoplasia. This gap prompted a new HEDIS measure requiring follow-up colonoscopy in 80% of patients with an abnormal test. That raises the question of who is responsible for the follow-up: the primary care physician, the gastroenterologist, or the payer. Dr. Shaukat said gastroenterologists need to educate payers, ensure easy access to high-quality colonoscopy, and become proficient in polypectomy. They should also support referral follow-through with metric-driven quality indicators, visible advocacy, and public education.

Dr. Shaukat concluded that CRC screening remains a challenge after 30 years of work. The field needs to focus on quality and push back against declining reimbursement. Putting these tests into practice will take work.