• Revised ACS guidelines expand CRC screening options but are intended to complement, not replace, existing methods.
• Personalized approaches with risk tools and AI assistance may bolster early detection.

Updated American Cancer Society guidance is reshaping colorectal cancer screening, expanding testing options and raising questions about where noninvasive tests, AI and risk-based screening fit alongside established approaches.

In its recently revised screening guidance, the American Cancer Society (ACS) included two new at-home stool tests and added a limited recommendation for blood-based screening for patients who decline other forms of screening.

The update has sparked concern from ACG, which warned that the new blood-based test guidelines could confuse patients and undermine adherence to higher-sensitivity screening options.

“Blood-based tests — which can detect circulating free DNA associated with colon cancer — are potentially the holy grail of colon cancer screening,” David Lieberman, MD, professor of gastroenterology and hepatology at Oregon Health & Science University and former AGA president, told Healio.

“If we could [screen] with a blood test, so that people don’t have to deal with stool or bowel prep before having a colonoscopy, that would be great,” he said. “However, the current versions of these tests fail to detect many early-stage cancers and advanced polyps, lesions we clearly want to detect to help prevent colon cancer.”

Lieberman said it was important to note that in published studies, blood-based tests underperform other screening options at detecting early-stage cancer and precancerous polyps.

“We hope these tests will get better as the science improves,” Lieberman said.

A recent CMS decision reflects the evolving landscape of CRC screening, designating fixed sensitivity and specificity thresholds to qualify noninvasive CRC biomarker tests for coverage, streamlining the process for any future options approved by the FDA.

“We all have a part to play in reducing the burden of colorectal cancer,” Shivan J. Mehta, MD, MBA, MSHP, associate professor of medicine and health policy and associate chief innovation officer at University of Pennsylvania Perelman School of Medicine, told Healio. “No one solution is going to solve the problem alone.”

While current guidelines rely largely on age and average-risk categories, researchers are exploring ways to refine screening decisions by incorporating additional markers of individual risk.

“An ideal [CRC] screening program would be risk-based,” Lieberman said. “We would reserve the most invasive, highest-risk procedures — which would be colonoscopies — for the highest-risk individuals, and use less invasive and risky tests for individuals at lower risk.”

However, clinicians currently do not have the tools to further stratify risk for CRC among individuals at average-risk.

In the near future, polygenic risk scores — based on genes associated with CRC development— may be able to address this issue and determine whether patients should opt for stool-based screening or colonoscopy, Lieberman noted.

“When we break down a large sample of individuals by these risk scores, the individuals at the very lowest end of the score have a very low risk of developing colon cancer, whereas the individuals on the high end have a high risk,” he said. “For the people in the middle we’re still a little less sure about it, but I think we’re on the cusp of being able to use this kind of information to help risk stratify.”

Fecal immunochemical tests, which detect human hemoglobin in a stool sample, also have the potential to provide a more precise risk-stratification assessment.

“Right now, the test is reported as a yes or a no. If it reaches a certain threshold, it’s considered positive, and if it doesn’t reach that threshold, it’s considered negative,” Lieberman said. “But what if we used the quantitative information — the absolute value of the human hemoglobin? That is potentially a tool that could be applied to help us understand who might be at higher risk and who might be a lower risk.”

Clinicians now have the added challenge of deciding where blood-based CRC tests fit into screening efforts.

“The new ACS guidelines say that [blood-based tests] should be offered if patients decline or are not able to participate in other screening options,” Mehta said. “If we are now able to test a patient who wouldn’t have ordinarily gotten screened because they didn’t want to complete the other screening options, that would be beneficial.”

However, blood-based tests should be “a complement, not a substitute,” he emphasized. Colonoscopy remains the most comprehensive test for screening and is the only method that also allows for the removal of polyps.

“Patients develop precancerous lesions and polyps in their colon before they develop cancer,” Lieberman said. “If we can detect the highest risk polyps and remove them, then we have the potential to prevent cancer.”

Current screening standards dictate that clinicians should offer all average-risk individuals colonoscopy or stool-based tests at set intervals, but there are still challenges with uptake and adherence.

When a patient at average risk receives a negative colonoscopy result, they generally do not have to return for screening for 10 years.

“For stool-based testing, patients have to come back every 1 to 3 years, and the challenge is that life gets in the way,” Mehta said. “Unless there is a systematic or organized program to send outreach, many of those patients forget about it.”

Mehta highlighted the importance of patient outreach programs to ensure adherence and follow-up.

“When Kaiser Permanente in Northern California implemented a population health strategy of mailing stool testing kits to their patients, they found that it reduced the incidence of colorectal cancer, improved outcomes and eliminated disparities between Black and non-Black patients,” he said.

Black individuals in the U.S. face higher CRC incidence and mortality rates than white individuals, as well as disparities in screening rates, as Healio previously reported.

Patients living in rural areas face similar disparities, an issue that can be mitigated by providing telehealth and patient navigation services, according to Lieberman.

Navigation services are particularly important to ensure rural patients complete follow-up colonoscopies after noninvasive screening tests yield positive results.

“Getting that patient to a colonoscopy in a rural community can be challenging,” Lieberman said.

The emergence of AI-assistive technologies have also had an impact on the CRC screening landscape.

“In the realm of colorectal cancer screening, the most mature aspect of AI has been polyp detection during colonoscopy,” Mehta said.

Lieberman said his personal experience with AI-assisted colonoscopy aligns with broader studies, which indicate AI tools are most helpful at detecting small polyps.

“One might argue that has some value, but questionable value, because most small polyps never grow into big problems,” Lieberman said.

Existing AI-assisted colonoscopy tools may be most helpful to clinicians with lower adenoma detection rates, Lieberman said.

Mehta also emphasized the importance of adenoma detection rate (ADR) as the primary benchmark for gastroenterologists.

“When patients or primary care doctors are referring people to a gastroenterologist, the most important thing to know is whether they track their quality metrics,” he said.
The AI part is secondary. If they use AI technology to help them, then that can be useful. If they don’t use it, but still have a higher ADR, that’s also reasonable.”

In 2021, the U.S. Preventive Services Task Force shifted the recommended CRC screening age from 50 years to 45 years, recognizing an increase in early-onset CRC incidence.

“Primary care physicians need to start having discussions with patients about screening before age 45,” Lieberman said.

He recommends clinicians obtain a complete family history of cancer, colon cancer and advanced polyps as patients approach screening age.

“[High-risk] individuals need to get screened at an earlier age, so we need to be more vigilant about identifying them,” Mehta said.

Mehta also highlighted the importance of watching out for CRC symptoms — including rectal bleeding and iron deficiency anemia — in younger patients.

Given the rise in early-onset CRC, “when younger people have rectal bleeding, we’re going to be more fastidious about making sure they get a colonoscopy,” Mehta said.

David Lieberman, MD, can be reached at lieberma@ohsu.edu.

Shivan J. Mehta, MD, MBA, MSHP, can be reached at shivan.mehta@pennmedicine.upenn.edu.