First-Line Options for CRC Screening: Stool-Based Screening Versus Colonoscopy

SAN FRANCISCO—For colorectal cancer prevention, stool-based testing should be a first-line option rather than just an alternative to colonoscopy, according to Theodore R. Levin, MD, the clinical lead for colorectal cancer screening and the associate director for cancer research at the Kaiser Permanente Division of Research, in Oakland, Calif.

“Stool-based testing is particularly valuable for organized screening where you can do mailed outreach to a large population of patients. Colonoscopy is still important, but I don’t think it works as a population approach. It works much better when there is a physician making a face-to-face recommendation, but many people just don’t come to the doctor,” Dr. Levin said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium. “Stool-based testing provides a very convenient way to reach more patients.”

FIT Reduces Mortality

Stool-based testing has long been viewed as a means of detection and not prevention, but studies establishing it as such are “outdated,” Dr. Levin said. More recent data suggest that the fecal immunochemical test (FIT) can also lower both the incidence of and mortality related to colorectal cancer, he said.

The Cancer Intervention and Surveillance Modeling Network has estimated the number of CRC deaths averted by either colonoscopy every 10 years or annual FIT (with follow-up colonoscopy if needed). At 100% adherence to testing, deaths averted per 1,000 individuals numbered 25 for FIT and 27 for colonoscopy, after 1,496 versus 3,464 lifetime colonoscopies, respectively (JAMA 2021;325[19]:1998-2011).

“This amounted to two additional deaths saved per essentially twice as many colonoscopies, with colonoscopy screening,” Dr. Levin noted.

“It’s really about adherence,” he said, and multiple trials have demonstrated far greater adherence to noninvasive testing. For example, he said, in the COLONPREV trial, colonoscopy detected twice as many advanced adenomas, but FIT every two years detected slightly more cancers because adherence was much better (N Engl J Med 366[8]:697-706). Similarly, in the randomized SCREESCO trial of a single colonoscopy versus two rounds of FIT, the cancer detection rate was 0.16% with colonoscopy and 0.20% with FIT (hazard ratio [HR], 0.78)—a finding attributed to its 55% adherence rate versus 35% for colonoscopy (Lancet Gastroenterol Hepatol 2022;7[6]:513-521). Finally, the PICCOLINO study randomized adults to colonoscopy only, colonoscopy and subsequent FIT in those who did not respond to the colonoscopy invitation, or choice between colonoscopy and FIT. The diagnostic yield for advanced neoplasia was similar (1.1%-1.2%), but participation was far greater in patients given a choice (Gastroenterology 2021;160[4]:1097-1105).

Mailed FIT Program

Dr. Levin and his co-investigators launched a mailed FIT outreach program that examined outcomes in FIT users and patients referred for screening colonoscopy (Gastroenterology 2018;155[5]:1383-1391). The organized screening significantly increased the percentage of patients who were up-to-date with screening, from about 39% to 83%. Higher rates of screening were associated with a 25% reduction in annual CRC incidence and a 52% reduction in CRC mortality—mostly driven by high uptake of FIT, he said.

“We’ve also demonstrated that giving consistent care using a population-based organized screening approach—where you remind everyone, regardless of race or ethnicity or whether they are coming into the office (as required for colonoscopy referral)—you can close gaps in incidence and mortality between white and black patients [N Engl J Med 2022;386(8):796-798],” he added.

“We believe that in an environment where you may get higher participation with FIT—with regular invitations, reminders and tracking so that people with a positive FIT get a colonoscopy—FIT can at least be noninferior to colonoscopy,” Dr. Levin maintained.

What About mt-sDNA Testing?

Dr. Levin acknowledged that stool-based testing with the multi-targeted stool DNA (mt-sDNA) test (Cologuard, Exact Sciences) also has become an attractive alternative for patients. Compared with FIT, mt-sDNA has higher sensitivity but lower specificity; costs substantially more ($600 vs. $25); is sent via United Parcel Service, not mailed; is performed every three years instead of annually; and offers a patient navigator. Importantly, mt-sDNA is considered by the U.S. Multi-Society Task Force on Colorectal Cancer to be a second-tier test, while FIT is top-tier. “FIT is deemed equivalent to colonoscopy by the Multi-Society Task Force,” he noted.

Is the test better than FIT? In a simulation model, Ladabaum et al demonstrated that mt-sDNA administered every three years was actually less effective than annual FIT (Gastroenterology 2016;151[3]:427-439). The researchers showed that for mt-sDNA to become cost-effective, participation would need to increase 1.7-fold or the cost would need to drop by 60%.

Will Providers Choose FIT Over Colonoscopy?

With colonoscopy being an economic driver in community practices, is it reasonable to expect providers to choose FIT screening for their average-risk patients? Aasma Shaukat, MD, MPH, the Robert M. and Mary H. Glickman Professor of Medicine, a professor of population health, and the director of GI Outcomes Research at NYU Grossman School of Medicine, in New York City, said she believes there is actually little to lose, economically, with stool-based screening.

“The number of colonoscopies over 10 years actually increases with FIT screening because stool-based tests don’t do anything by themselves. It’s the ones that are positive, where patients undergo colonoscopy. Our group has done a back-of-the-envelope calculation and [has] found that if you account for the additional number of screening participants and a test positivity rate of 5% to 7% per round, you get a steady stream of about 3 million colonoscopies per year in the U.S. Over 10 years, a provider would actually do more colonoscopies versus one at each end,” she said.

If the ideal of screening every eligible adult is ultimately realized, this approach could also “absorb the capacity” that would be created, she added. “Some 41% of individuals still need screening, and for this we would need 29 million colonoscopies. Even the most resourceful settings do not have that capacity. The best approach is a combination of tests.”

—Caroline Helwick

Dr. Levin reported research support from Freenome and Universal Diagnostics. Dr. Shaukat reported financial relationships with Freenome, Guardant Health and Iterative Health.