16-05-2025
Colorectal Cancer Screening Choices: Is Compliance Key?
SAN DIEGO — In the ever-expanding options for colorectal cancer (CRC) screening, blood tests using precision medicine are becoming more advanced and convenient than ever; however, caveats abound, and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.
Regarding tests, 'perfect is not possible,' said William M. Grady, MD, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week (DDW) 2025.
'We have to remember that that's the reality of colorectal cancer screening, and we need to meet our patients where they live,' said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).
A big point in their favor is their convenience and higher patient compliance — better tests that don't get done do not work, he stressed.
He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.
With troubling increases in CRC incidence among younger patients, 'that's a group we're particularly concerned about,' Grady said.
Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.
Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.
'What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,' he said.
Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).
'The bottom line is that these tests decrease CRC mortality and incidence, and we know there's a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,' Grady said.
Blood-Based Tests: Caveats, Harms?
Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, Pittsburgh, checked off some of the key caveats.
While the overall sensitivity of blood-based tests may look favorable, these tests don't detect early CRC well,' said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.
Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.
These rates are 'similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,' Schoen said. 'Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].'
Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.
Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.
He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.
'We have a long way to go to make sure that people who get positive noninvasive tests get followed up,' he said.
In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.
Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.
Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, 'the rate of CRC deaths would increase,' Schoen noted.
The findings underscore that 'blood testing is unfavorable as a 'substitution test,'' he added. 'In fact, widespread adoption of blood testing could increase CRC morbidity.'
'Is it better than nothing?' he asked. 'Yes, but only if performance of a colonoscopy after a positive test is accomplished.'
What About FIT?
Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.
Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.
In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.
Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).
'This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,' Tinmouth said.
Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.
'FIT has clear and compelling advantages over colonoscopy,' she said. As well as better compliance among all groups, 'it is less costly and also better for the environment [by using fewer resources],' she added.
Colonoscopy: 'Best for First-Line Screening'
Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.
A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.
In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said.
Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.
Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.
'Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,' she said.
Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study's appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.
The collective findings underscore that 'colonoscopy as a standalone test is uniquely cost-effective,' in the face of costs related to colon cancer treatment.
Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.
