GI and Hepatology News

The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.

While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?

A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.

 

What the Study Found

The new analysis found that childhood exposure to a carcinogenic toxin known to cause DNA damage is strongly linked to the development of early-onset CRC.

The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.

In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.

Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.

Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.

However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.

“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.

“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”

 

What the Study Means

Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.

Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”

Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”

“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”

Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”

However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.

But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.

If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.

There are also clinical implications if the findings pan out, Venook said.

This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”

The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.

A version of this article appeared on Medscape.com.

The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.

While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?

A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.

 

What the Study Found

The new analysis found that childhood exposure to a carcinogenic toxin known to cause DNA damage is strongly linked to the development of early-onset CRC.

The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.

In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.

Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.

Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.

However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.

“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.

“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”

 

What the Study Means

Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.

Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”

Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”

“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”

Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”

However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.

But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.

If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.

There are also clinical implications if the findings pan out, Venook said.

This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”

The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.

A version of this article appeared on Medscape.com.

The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.

While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?

A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.

 

What the Study Found

The new analysis found that childhood exposure to a carcinogenic toxin known to cause DNA damage is strongly linked to the development of early-onset CRC.

The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.

In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.

Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.

Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.

However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.

“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.

“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”

 

What the Study Means

Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.

Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”

Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”

“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”

Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”

However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.

But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.

If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.

There are also clinical implications if the findings pan out, Venook said.

This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”

The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.

A version of this article appeared on Medscape.com.

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, AGAF, 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, in Pittsburgh, Pennsylvania, 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.

Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.

A version of this article appeared on Medscape.com.

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, AGAF, 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, in Pittsburgh, Pennsylvania, 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.

Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.

A version of this article appeared on Medscape.com.

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, AGAF, 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, in Pittsburgh, Pennsylvania, 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.

Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.

A version of this article appeared on Medscape.com.

SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?

Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.

Surveillance endoscopy every 2 years offers no benefit in terms of overall or cancer-specific survival, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week^® (DDW) 2025.

At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.

 

The BOSS Trial

The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.

Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.

The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.

Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.

Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.

“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.

Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.

The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.

Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.

 

Will BOSS Change Minds?

Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.

However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”

The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.

Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”

Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.

Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.

While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”

The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?

Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.

Surveillance endoscopy every 2 years offers no benefit in terms of overall or cancer-specific survival, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week^® (DDW) 2025.

At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.

 

The BOSS Trial

The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.

Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.

The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.

Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.

Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.

“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.

Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.

The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.

Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.

 

Will BOSS Change Minds?

Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.

However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”

The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.

Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”

Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.

Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.

While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”

The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?

Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.

Surveillance endoscopy every 2 years offers no benefit in terms of overall or cancer-specific survival, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week^® (DDW) 2025.

At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.

 

The BOSS Trial

The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.

Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.

The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.

Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.

Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.

“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.

Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.

The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.

Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.

 

Will BOSS Change Minds?

Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.

However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”

The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.

Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”

Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.

Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.

While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”

The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The majority of colorectal cancers (CRCs) that emerge following a negative colonoscopy and polypectomy occur prior to recommended surveillance exams, and those cases are more likely to be at an advanced stage, according to new research.

Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.

“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.

“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”

Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.

“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.

In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.

The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.

Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).

Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.

 

Colonoscopist Skill and Benchmarks

A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).

Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).

“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.

“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.

The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.

They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.

And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”

Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.

She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).

“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”

Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.

 

Patient Compliance Can’t Be Counted On 

In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.

“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.

One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.

This underscores the need for better prevention as well as follow-up strategies, he added.

Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.

A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.

While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.

Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.

The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.

Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.

 

FIT Tests Potentially a ‘Major Advantage’

“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.

“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.

More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.

“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.

Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”

Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.

A version of this article appeared on Medscape.com.

SAN DIEGO — The majority of colorectal cancers (CRCs) that emerge following a negative colonoscopy and polypectomy occur prior to recommended surveillance exams, and those cases are more likely to be at an advanced stage, according to new research.

Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.

“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.

“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”

Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.

“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.

In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.

The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.

Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).

Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.

 

Colonoscopist Skill and Benchmarks

A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).

Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).

“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.

“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.

The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.

They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.

And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”

Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.

She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).

“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”

Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.

 

Patient Compliance Can’t Be Counted On 

In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.

“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.

One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.

This underscores the need for better prevention as well as follow-up strategies, he added.

Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.

A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.

While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.

Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.

The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.

Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.

 

FIT Tests Potentially a ‘Major Advantage’

“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.

“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.

More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.

“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.

Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”

Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.

A version of this article appeared on Medscape.com.

SAN DIEGO — The majority of colorectal cancers (CRCs) that emerge following a negative colonoscopy and polypectomy occur prior to recommended surveillance exams, and those cases are more likely to be at an advanced stage, according to new research.

Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.

“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.

“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”

Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.

“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.

In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.

The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.

Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).

Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.

 

Colonoscopist Skill and Benchmarks

A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).

Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).

“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.

“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.

The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.

They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.

And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”

Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.

She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).

“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”

Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.

 

Patient Compliance Can’t Be Counted On 

In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.

“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.

One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.

This underscores the need for better prevention as well as follow-up strategies, he added.

Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.

A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.

While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.

Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.

The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.

Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.

 

FIT Tests Potentially a ‘Major Advantage’

“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.

“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.

More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.

“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.

Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”

Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.

A version of this article appeared on Medscape.com.

SAN DIEGO – Advanced practice providers (APPs) can be trained to perform transnasal endoscopy (TNE) with a single-use ultra-slim gastroscope with only topical anesthesia, a pilot study showed.

“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.

“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.

The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.

The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.

Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.

Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.

TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).

Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.

Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.

Technical success was achieved in all but one patient (96%), and there were no adverse events.

All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.

The average TNE procedure time was 7.3 minutes.

TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.

The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.

“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.

 

Caveats and Cautionary Notes

Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”

Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.

“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.

“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.

The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.

A version of this article appeared on Medscape.com.

SAN DIEGO – Advanced practice providers (APPs) can be trained to perform transnasal endoscopy (TNE) with a single-use ultra-slim gastroscope with only topical anesthesia, a pilot study showed.

“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.

“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.

The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.

The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.

Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.

Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.

TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).

Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.

Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.

Technical success was achieved in all but one patient (96%), and there were no adverse events.

All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.

The average TNE procedure time was 7.3 minutes.

TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.

The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.

“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.

 

Caveats and Cautionary Notes

Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”

Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.

“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.

“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.

The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.

A version of this article appeared on Medscape.com.

SAN DIEGO – Advanced practice providers (APPs) can be trained to perform transnasal endoscopy (TNE) with a single-use ultra-slim gastroscope with only topical anesthesia, a pilot study showed.

“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.

“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.

The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.

The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.

Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.

Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.

TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).

Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.

Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.

Technical success was achieved in all but one patient (96%), and there were no adverse events.

All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.

The average TNE procedure time was 7.3 minutes.

TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.

The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.

“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.

 

Caveats and Cautionary Notes

Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”

Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.

“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.

“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.

The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.

A version of this article appeared on Medscape.com.

SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.

“This is the first study implementing multi-biomarker signatures in informed decisions instead of single biomarker–based trial algorithms [in IBD],” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.

“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.

Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.

In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.

“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.

Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.

To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.

All patients had been assigned the anti-TNF drug infliximab for the first time.

Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.

Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.

The assessments also looked at infliximab and anti-drug antibody levels.

Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.

Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.

The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).

A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.

For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).

Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).

An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.

More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).

“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.

The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.

 

Approach Pioneered in Oncology

Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.

“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.

Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.

The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.” 

 

Benefits in Other IBD Therapies Unclear

Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”

Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”

While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.

“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.

How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.

Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.

“This is the first study implementing multi-biomarker signatures in informed decisions instead of single biomarker–based trial algorithms [in IBD],” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.

“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.

Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.

In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.

“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.

Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.

To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.

All patients had been assigned the anti-TNF drug infliximab for the first time.

Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.

Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.

The assessments also looked at infliximab and anti-drug antibody levels.

Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.

Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.

The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).

A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.

For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).

Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).

An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.

More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).

“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.

The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.

 

Approach Pioneered in Oncology

Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.

“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.

Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.

The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.” 

 

Benefits in Other IBD Therapies Unclear

Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”

Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”

While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.

“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.

How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.

Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.

“This is the first study implementing multi-biomarker signatures in informed decisions instead of single biomarker–based trial algorithms [in IBD],” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.

“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.

Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.

In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.

“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.

Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.

To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.

All patients had been assigned the anti-TNF drug infliximab for the first time.

Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.

Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.

The assessments also looked at infliximab and anti-drug antibody levels.

Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.

Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.

The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).

A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.

For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).

Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).

An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.

More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).

“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.

The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.

 

Approach Pioneered in Oncology

Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.

“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.

Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.

The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.” 

 

Benefits in Other IBD Therapies Unclear

Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”

Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”

While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.

“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.

How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.

Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — Boston Pharmaceuticals’ once-monthly efimosfermin alfa (formerly BOS-580) prescribed for metabolic dysfunction–associated steatohepatitis (MASH) with F2 and F3 fibrosis significantly improved MASH resolution and fibrosis after 24 weeks, according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.

An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.

MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.

The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.

The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.

Primary endpoints were safety and tolerability.

Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.

Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.

 

Positive Results

“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”

After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).

The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.

Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.

Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.

“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.

 

Hopeful Development

“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.

The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.

Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.

Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — Boston Pharmaceuticals’ once-monthly efimosfermin alfa (formerly BOS-580) prescribed for metabolic dysfunction–associated steatohepatitis (MASH) with F2 and F3 fibrosis significantly improved MASH resolution and fibrosis after 24 weeks, according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.

An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.

MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.

The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.

The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.

Primary endpoints were safety and tolerability.

Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.

Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.

 

Positive Results

“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”

After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).

The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.

Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.

Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.

“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.

 

Hopeful Development

“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.

The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.

Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.

Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.

A version of this article appeared on Medscape.com.

SAN DIEGO — Boston Pharmaceuticals’ once-monthly efimosfermin alfa (formerly BOS-580) prescribed for metabolic dysfunction–associated steatohepatitis (MASH) with F2 and F3 fibrosis significantly improved MASH resolution and fibrosis after 24 weeks, according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.

An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.

MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.

The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.

The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.

Primary endpoints were safety and tolerability.

Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.

Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.