GI Oncology

Early-onset gastrointestinal (GI) cancers diagnosed before age 50 are rising at alarming rates worldwide, underscoring the need for enhanced prevention strategies and early detection, said the authors of a JAMA review.

In the US, early-onset GI cancers are increasing faster than any other type of early-onset cancer, including breast cancer. The trend is not limited to colorectal cancer (CRC). Gastric, pancreatic, esophageal, as well as many biliary tract and appendix cancers, are also on the rise in young adults, Kimmie Ng, MD, MPH, and Thejus Jayakrishnan, MD, both with Dana-Farber Cancer Institute, Boston, noted in their article.

The increase in early-onset GI cancers follows a “birth cohort effect,” with generational variation in risk, suggesting a potential association with changes in environmental exposures, Ng explained in an accompanying JAMA podcast.

All these GI cancers link strongly to multiple modifiable risk factors, and it is a “top area of investigation to determine exactly what environmental exposures are at play,” Ng added.

For many of these GI cancers, obesity has been the “leading hypothesis” given that rising rates seem to parallel the increase in incidence of these early-onset GI cancers, Ng explained.

“But we also have evidence, particularly strong for colorectal cancer, that dietary patterns, such as consuming a Western diet, as well as sedentary behavior and lifestyles seem to be associated with a significantly higher risk of developing these cancers at an age under 50,” Ng said.

 

Rising Incidence 

Globally, among early-onset GI cancers reported in 2022, CRC was the most common (54%), followed by gastric cancer (24%), esophageal cancer (13%), and pancreatic cancer (9%).

In the US in 2022, 20,805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric cancer, 2657 with early-onset pancreatic cancer, and 875 with early-onset esophageal cancer.

Since the mid-1990s, CRC among adults of all ages in the US declined by 1.3%-4.2% annually but early-onset CRC increased by roughly 2% per year in both men and women, and currently makes up about 14% of all CRC cases.

Early-onset pancreatic cancer and esophageal cancer each currently make up about 5% of all cases of these cancers in the US.

Between 2010 and 2019, the number of newly diagnosed cases of early-onset GI cancers rose by nearly about 15%, with Black, Hispanic, Indigenous ancestry, and women disproportionately affected, Ng and coauthors noted in a related review published in the British Journal of Surgery.

 

Modifiable and Nonmodifiable Risk Factors 

Along with obesity and poor diet, other modifiable risk factors for early-onset GI cancers include sedentary lifestyle, cigarette smoking, and alcohol consumption.

Nonmodifiable risk factors include family history, hereditary cancer syndromes such as Lynch syndrome and inflammatory bowel disease.

Roughly 15%-30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2.

All individuals with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk, Ng and Jayakrishnan advised.

 

Treatment Challenges

Treatment for early-onset GI cancers is generally similar to later-onset GI cancers and prognosis for patients with early-onset GI cancers is “similar to or worse” than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection, the authors said.

Ng noted that younger cancer patients often face more challenges after diagnosis than older patients and benefit from multidisciplinary care, including referral for fertility counseling and preservation if appropriate, and psychosocial support.

“It is very difficult and challenging to receive a cancer diagnosis no matter what age you are, but when a person is diagnosed in their 20s, 30s, or 40s, there are unique challenges,” Ng said.

Studies have documented “much higher levels of psychosocial distress, depression and anxiety” in early-onset cancer patients, “and they also often experience more financial toxicity, disruptions in their education as well as their career and there may be fertility concerns,” Ng added.

 

Diagnostic Delays and Screening

Currently, screening is not recommended for most early-onset GI cancers — with the exception of CRC, with screening recommended for average-risk adults in the US starting at age 45.

Yet, despite this recommendation, fewer than 1 in 5 (19.7%) US adults aged 45-49 years were screened in 2021, indicating a significant gap in early detection efforts.

High-risk individuals, such as those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma, should begin CRC screening earlier, at an age determined by the specific risk factor.

“Studies have shown significant delays in diagnosis among younger patients. It’s important that prompt diagnosis happens so that these patients do not end up being diagnosed with advanced or metastatic stages of cancer, as they often are,” Ng said.

“Screening adherence is absolutely critical,” co-author Jayakrishnan added in a news release.

“We have strong evidence that colorectal cancer screening saves lives by reducing both the number of people who develop colorectal cancer and the number of people who die from it. Each missed screening is a lost opportunity to detect cancer early when it is more treatable, or to prevent cancer altogether by identifying and removing precancerous polyps,” Jayakrishnan said.This research had no funding. Ng reported receipt of nonfinancial support from Pharmavite, institutional grants from Janssen, and personal fees from Bayer, Seagen, GlaxoSmithKline, Pfizer, CytomX, Jazz Pharmaceuticals, Revolution Medicines, Redesign Health, AbbVie, Etiome, and CRICO. Ng is an associate editor of JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Jayakrishnan had no disclosures.

A version of this article appeared on Medscape.com.

Early-onset gastrointestinal (GI) cancers diagnosed before age 50 are rising at alarming rates worldwide, underscoring the need for enhanced prevention strategies and early detection, said the authors of a JAMA review.

In the US, early-onset GI cancers are increasing faster than any other type of early-onset cancer, including breast cancer. The trend is not limited to colorectal cancer (CRC). Gastric, pancreatic, esophageal, as well as many biliary tract and appendix cancers, are also on the rise in young adults, Kimmie Ng, MD, MPH, and Thejus Jayakrishnan, MD, both with Dana-Farber Cancer Institute, Boston, noted in their article.

The increase in early-onset GI cancers follows a “birth cohort effect,” with generational variation in risk, suggesting a potential association with changes in environmental exposures, Ng explained in an accompanying JAMA podcast.

All these GI cancers link strongly to multiple modifiable risk factors, and it is a “top area of investigation to determine exactly what environmental exposures are at play,” Ng added.

For many of these GI cancers, obesity has been the “leading hypothesis” given that rising rates seem to parallel the increase in incidence of these early-onset GI cancers, Ng explained.

“But we also have evidence, particularly strong for colorectal cancer, that dietary patterns, such as consuming a Western diet, as well as sedentary behavior and lifestyles seem to be associated with a significantly higher risk of developing these cancers at an age under 50,” Ng said.

 

Rising Incidence 

Globally, among early-onset GI cancers reported in 2022, CRC was the most common (54%), followed by gastric cancer (24%), esophageal cancer (13%), and pancreatic cancer (9%).

In the US in 2022, 20,805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric cancer, 2657 with early-onset pancreatic cancer, and 875 with early-onset esophageal cancer.

Since the mid-1990s, CRC among adults of all ages in the US declined by 1.3%-4.2% annually but early-onset CRC increased by roughly 2% per year in both men and women, and currently makes up about 14% of all CRC cases.

Early-onset pancreatic cancer and esophageal cancer each currently make up about 5% of all cases of these cancers in the US.

Between 2010 and 2019, the number of newly diagnosed cases of early-onset GI cancers rose by nearly about 15%, with Black, Hispanic, Indigenous ancestry, and women disproportionately affected, Ng and coauthors noted in a related review published in the British Journal of Surgery.

 

Modifiable and Nonmodifiable Risk Factors 

Along with obesity and poor diet, other modifiable risk factors for early-onset GI cancers include sedentary lifestyle, cigarette smoking, and alcohol consumption.

Nonmodifiable risk factors include family history, hereditary cancer syndromes such as Lynch syndrome and inflammatory bowel disease.

Roughly 15%-30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2.

All individuals with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk, Ng and Jayakrishnan advised.

 

Treatment Challenges

Treatment for early-onset GI cancers is generally similar to later-onset GI cancers and prognosis for patients with early-onset GI cancers is “similar to or worse” than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection, the authors said.

Ng noted that younger cancer patients often face more challenges after diagnosis than older patients and benefit from multidisciplinary care, including referral for fertility counseling and preservation if appropriate, and psychosocial support.

“It is very difficult and challenging to receive a cancer diagnosis no matter what age you are, but when a person is diagnosed in their 20s, 30s, or 40s, there are unique challenges,” Ng said.

Studies have documented “much higher levels of psychosocial distress, depression and anxiety” in early-onset cancer patients, “and they also often experience more financial toxicity, disruptions in their education as well as their career and there may be fertility concerns,” Ng added.

 

Diagnostic Delays and Screening

Currently, screening is not recommended for most early-onset GI cancers — with the exception of CRC, with screening recommended for average-risk adults in the US starting at age 45.

Yet, despite this recommendation, fewer than 1 in 5 (19.7%) US adults aged 45-49 years were screened in 2021, indicating a significant gap in early detection efforts.

High-risk individuals, such as those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma, should begin CRC screening earlier, at an age determined by the specific risk factor.

“Studies have shown significant delays in diagnosis among younger patients. It’s important that prompt diagnosis happens so that these patients do not end up being diagnosed with advanced or metastatic stages of cancer, as they often are,” Ng said.

“Screening adherence is absolutely critical,” co-author Jayakrishnan added in a news release.

“We have strong evidence that colorectal cancer screening saves lives by reducing both the number of people who develop colorectal cancer and the number of people who die from it. Each missed screening is a lost opportunity to detect cancer early when it is more treatable, or to prevent cancer altogether by identifying and removing precancerous polyps,” Jayakrishnan said.This research had no funding. Ng reported receipt of nonfinancial support from Pharmavite, institutional grants from Janssen, and personal fees from Bayer, Seagen, GlaxoSmithKline, Pfizer, CytomX, Jazz Pharmaceuticals, Revolution Medicines, Redesign Health, AbbVie, Etiome, and CRICO. Ng is an associate editor of JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Jayakrishnan had no disclosures.

A version of this article appeared on Medscape.com.

Early-onset gastrointestinal (GI) cancers diagnosed before age 50 are rising at alarming rates worldwide, underscoring the need for enhanced prevention strategies and early detection, said the authors of a JAMA review.

In the US, early-onset GI cancers are increasing faster than any other type of early-onset cancer, including breast cancer. The trend is not limited to colorectal cancer (CRC). Gastric, pancreatic, esophageal, as well as many biliary tract and appendix cancers, are also on the rise in young adults, Kimmie Ng, MD, MPH, and Thejus Jayakrishnan, MD, both with Dana-Farber Cancer Institute, Boston, noted in their article.

The increase in early-onset GI cancers follows a “birth cohort effect,” with generational variation in risk, suggesting a potential association with changes in environmental exposures, Ng explained in an accompanying JAMA podcast.

All these GI cancers link strongly to multiple modifiable risk factors, and it is a “top area of investigation to determine exactly what environmental exposures are at play,” Ng added.

For many of these GI cancers, obesity has been the “leading hypothesis” given that rising rates seem to parallel the increase in incidence of these early-onset GI cancers, Ng explained.

“But we also have evidence, particularly strong for colorectal cancer, that dietary patterns, such as consuming a Western diet, as well as sedentary behavior and lifestyles seem to be associated with a significantly higher risk of developing these cancers at an age under 50,” Ng said.

 

Rising Incidence 

Globally, among early-onset GI cancers reported in 2022, CRC was the most common (54%), followed by gastric cancer (24%), esophageal cancer (13%), and pancreatic cancer (9%).

In the US in 2022, 20,805 individuals were diagnosed with early-onset CRC, 2689 with early-onset gastric cancer, 2657 with early-onset pancreatic cancer, and 875 with early-onset esophageal cancer.

Since the mid-1990s, CRC among adults of all ages in the US declined by 1.3%-4.2% annually but early-onset CRC increased by roughly 2% per year in both men and women, and currently makes up about 14% of all CRC cases.

Early-onset pancreatic cancer and esophageal cancer each currently make up about 5% of all cases of these cancers in the US.

Between 2010 and 2019, the number of newly diagnosed cases of early-onset GI cancers rose by nearly about 15%, with Black, Hispanic, Indigenous ancestry, and women disproportionately affected, Ng and coauthors noted in a related review published in the British Journal of Surgery.

 

Modifiable and Nonmodifiable Risk Factors 

Along with obesity and poor diet, other modifiable risk factors for early-onset GI cancers include sedentary lifestyle, cigarette smoking, and alcohol consumption.

Nonmodifiable risk factors include family history, hereditary cancer syndromes such as Lynch syndrome and inflammatory bowel disease.

Roughly 15%-30% of early-onset GI cancers have pathogenic germline variants in genes such as DNA mismatch repair genes and BRCA1/2.

All individuals with early-onset GI cancers should undergo germline and somatic genetic testing to guide treatment, screen for other cancers (eg, endometrial cancer in Lynch syndrome), and assess familial risk, Ng and Jayakrishnan advised.

 

Treatment Challenges

Treatment for early-onset GI cancers is generally similar to later-onset GI cancers and prognosis for patients with early-onset GI cancers is “similar to or worse” than that for patients with later-onset GI cancers, highlighting the need for improved methods of prevention and early detection, the authors said.

Ng noted that younger cancer patients often face more challenges after diagnosis than older patients and benefit from multidisciplinary care, including referral for fertility counseling and preservation if appropriate, and psychosocial support.

“It is very difficult and challenging to receive a cancer diagnosis no matter what age you are, but when a person is diagnosed in their 20s, 30s, or 40s, there are unique challenges,” Ng said.

Studies have documented “much higher levels of psychosocial distress, depression and anxiety” in early-onset cancer patients, “and they also often experience more financial toxicity, disruptions in their education as well as their career and there may be fertility concerns,” Ng added.

 

Diagnostic Delays and Screening

Currently, screening is not recommended for most early-onset GI cancers — with the exception of CRC, with screening recommended for average-risk adults in the US starting at age 45.

Yet, despite this recommendation, fewer than 1 in 5 (19.7%) US adults aged 45-49 years were screened in 2021, indicating a significant gap in early detection efforts.

High-risk individuals, such as those with Lynch syndrome, a first-degree relative with CRC, or advanced colorectal adenoma, should begin CRC screening earlier, at an age determined by the specific risk factor.

“Studies have shown significant delays in diagnosis among younger patients. It’s important that prompt diagnosis happens so that these patients do not end up being diagnosed with advanced or metastatic stages of cancer, as they often are,” Ng said.

“Screening adherence is absolutely critical,” co-author Jayakrishnan added in a news release.

“We have strong evidence that colorectal cancer screening saves lives by reducing both the number of people who develop colorectal cancer and the number of people who die from it. Each missed screening is a lost opportunity to detect cancer early when it is more treatable, or to prevent cancer altogether by identifying and removing precancerous polyps,” Jayakrishnan said.This research had no funding. Ng reported receipt of nonfinancial support from Pharmavite, institutional grants from Janssen, and personal fees from Bayer, Seagen, GlaxoSmithKline, Pfizer, CytomX, Jazz Pharmaceuticals, Revolution Medicines, Redesign Health, AbbVie, Etiome, and CRICO. Ng is an associate editor of JAMA but was not involved in any of the decisions regarding review of the manuscript or its acceptance. Jayakrishnan had no disclosures.

A version of this article appeared on Medscape.com.

Private equity (PE) acquisition of gastroenterology (GI) practices led to higher colonoscopy prices, utilization, and spending with no commensurate effect on quality, an economic analysis found. Price increases ranged from about 5% to about 7%.

In view of the growing trend to such acquisitions, policy makers should monitor the impact of PE investment in medical practices, according to researchers led by health economist Daniel R. Arnold, PhD, of the Department of Health Services, Policy & Practice in the School of Public Health at Brown University in Providence, Rhode Island. “In a previous study of ours, gastroenterology stood out as a particularly attractive specialty to private equity,” Arnold told GI & Hepatology News.

Published in JAMA Health Forum, the economic evaluation of more than 1.1 million patients and 1.3 million colonoscopies concluded that PE acquisitions of GI sites are difficult to justify.

 

The Study

This difference-in-differences event study and economic evaluation analyzed data from US GI practices acquired by PE firms from 2015 to 2021. Commercial insurance claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021, with all data analyzed from April to September 2024.

The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality, as defined by polyp detection, incomplete colonoscopies, and four adverse event measures: cardiovascular, serious and nonserious GI events, and any other adverse events.

The mean age of patients was 47.1 years, and 47.8% were men. The sample included 718, 851 colonoscopies conducted by 1494 physicians in 590, 900 patients across 1240 PE-acquired practice sites and 637, 990 control colonoscopies conducted by 2550 physicians in 527,380 patients across 2657 independent practice sites.

Among the findings:

• Colonoscopy prices at PE-acquired sites increased by 4.5% (95% CI, 2.5-6.6; P < .001) vs independent practices. That increase was much lower than that reported by Singh and colleagues for  .
• The estimated price increase was 6.7% (95% CI, 4.2-9.3; P < .001) when only colonoscopies at PE practices with market shares above the 75th percentile (24.4%) in 2021 were considered. Both increases were in line with other research, Arnold said.
• Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3-19.4; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively. These measures, however, were already increasing before PE acquisition.
• No statistically significant associations were detected for the six quality measures analyzed.

Could such cost-raising acquisitions potentially be blocked by concerned regulators? 

“No. Generally the purchases are at prices below what would require notification to federal authorities,” Arnold said. “The Department of Justice/Federal Trade Commission hinted at being willing to look at serial acquisitions in their 2023 Merger Guidelines, but until that happens, these will likely continue to fly under the radar.”

Still, as evidence of PE-associated poorer quality outcomes as well as clinician burnout continues to emerge, Arnold added, “I would advise physicians who get buyout offers from PE to educate themselves on what could happen to patients and staff if they choose to sell.”

Offering an outsider’s perspective on the study, health economist Atul Gupta, PhD, an assistant professor of healthcare management in the Wharton School at the University of Pennsylvania in Philadelphia, called it an “excellent addition to the developing literature examining the effects of private equity ownership of healthcare providers.” Very few studies have examined the effects on prices and quality for the same set of deals and providers. “This is important because we want to be able to do an apples-to-apples comparison of the effects on both outcomes before judging PE ownership,” he told GI & Hepatology News.

In an accompanying editorial , primary care physician Jane M. Zhu, MD, an associate professor of medicine at Oregon Health & Science University in Portland, Oregon, and not involved in the commercial-insurance-based study, said one interpretation of the findings may be that PE acquisition focuses on reducing inefficiencies, improving access by expanding practice capacity, and increasing throughput. “Another interpretation may be that PE acquisition is focused on the strategic exploitation of market and pricing power. The latter may have less of an impact on clinical measures like quality of care, but potentially, both strategies could be at play.” 

Since this analysis focused on the commercial population, understanding how patient demographics may change after PE acquisition is a future avenue for exploration. “For instance, a potential explanation for both the price and utilization shifts might be if payer mix shifted toward more commercially insured patients at the expense of Medicaid or Medicare patients,” she wrote.

Zhu added that the impact of PE on prices and spending, by now replicated across different settings and specialties, is far clearer than the effect of PE on access and quality. “The analysis by Arnold et al is a welcome addition to the literature, generating important questions for future study and transparent monitoring as investor-owners become increasingly influential in healthcare.”

Going forward, said Gupta, an open question is whether the harmful effects of PE ownership of practices are differentially worse than those of other corporate entities such as insurers and hospital systems.

“There are reasons to believe that PE could be worse in theory. For example, their short-term investment horizon may force them to take measures that others will not as well as avoid investing into capital improvements that have a long-run payoff,” he said. “Their uniquely high dependence on debt and unbundling of real estate can severely hurt financial solvency of providers.” But high-quality evidence is lacking to compare the effects from these two distinct forms of corporatization.

The trend away from individual private practice is a reality, Arnold said. “The administrative burden on solo docs is becoming too much and physicians just seem to want to treat patients and not deal with it. So the options at this point really become selling to a hospital system or private equity.”

This study was funded by a grant from the philanthropic foundation Arnold Ventures (no family relation to Daniel Arnold). 

Arnold reported receiving grants from Arnold Ventures during the conduct of the study. Gupta had no competing interests to declare. Zhu reported receiving grants from the Agency for Healthcare Research and Quality during the submitted work and from the National Institutes of Health, National Institute for Health Care Management Foundation, and American Psychological Association, as well as personal fees from Cambia outside the submitted work.

A version of this article appeared on Medscape.com.

Private equity (PE) acquisition of gastroenterology (GI) practices led to higher colonoscopy prices, utilization, and spending with no commensurate effect on quality, an economic analysis found. Price increases ranged from about 5% to about 7%.

In view of the growing trend to such acquisitions, policy makers should monitor the impact of PE investment in medical practices, according to researchers led by health economist Daniel R. Arnold, PhD, of the Department of Health Services, Policy & Practice in the School of Public Health at Brown University in Providence, Rhode Island. “In a previous study of ours, gastroenterology stood out as a particularly attractive specialty to private equity,” Arnold told GI & Hepatology News.

Published in JAMA Health Forum, the economic evaluation of more than 1.1 million patients and 1.3 million colonoscopies concluded that PE acquisitions of GI sites are difficult to justify.

 

The Study

This difference-in-differences event study and economic evaluation analyzed data from US GI practices acquired by PE firms from 2015 to 2021. Commercial insurance claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021, with all data analyzed from April to September 2024.

The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality, as defined by polyp detection, incomplete colonoscopies, and four adverse event measures: cardiovascular, serious and nonserious GI events, and any other adverse events.

The mean age of patients was 47.1 years, and 47.8% were men. The sample included 718, 851 colonoscopies conducted by 1494 physicians in 590, 900 patients across 1240 PE-acquired practice sites and 637, 990 control colonoscopies conducted by 2550 physicians in 527,380 patients across 2657 independent practice sites.

Among the findings:

• Colonoscopy prices at PE-acquired sites increased by 4.5% (95% CI, 2.5-6.6; P < .001) vs independent practices. That increase was much lower than that reported by Singh and colleagues for  .
• The estimated price increase was 6.7% (95% CI, 4.2-9.3; P < .001) when only colonoscopies at PE practices with market shares above the 75th percentile (24.4%) in 2021 were considered. Both increases were in line with other research, Arnold said.
• Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3-19.4; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively. These measures, however, were already increasing before PE acquisition.
• No statistically significant associations were detected for the six quality measures analyzed.

Could such cost-raising acquisitions potentially be blocked by concerned regulators? 

“No. Generally the purchases are at prices below what would require notification to federal authorities,” Arnold said. “The Department of Justice/Federal Trade Commission hinted at being willing to look at serial acquisitions in their 2023 Merger Guidelines, but until that happens, these will likely continue to fly under the radar.”

Still, as evidence of PE-associated poorer quality outcomes as well as clinician burnout continues to emerge, Arnold added, “I would advise physicians who get buyout offers from PE to educate themselves on what could happen to patients and staff if they choose to sell.”

Offering an outsider’s perspective on the study, health economist Atul Gupta, PhD, an assistant professor of healthcare management in the Wharton School at the University of Pennsylvania in Philadelphia, called it an “excellent addition to the developing literature examining the effects of private equity ownership of healthcare providers.” Very few studies have examined the effects on prices and quality for the same set of deals and providers. “This is important because we want to be able to do an apples-to-apples comparison of the effects on both outcomes before judging PE ownership,” he told GI & Hepatology News.

In an accompanying editorial , primary care physician Jane M. Zhu, MD, an associate professor of medicine at Oregon Health & Science University in Portland, Oregon, and not involved in the commercial-insurance-based study, said one interpretation of the findings may be that PE acquisition focuses on reducing inefficiencies, improving access by expanding practice capacity, and increasing throughput. “Another interpretation may be that PE acquisition is focused on the strategic exploitation of market and pricing power. The latter may have less of an impact on clinical measures like quality of care, but potentially, both strategies could be at play.” 

Since this analysis focused on the commercial population, understanding how patient demographics may change after PE acquisition is a future avenue for exploration. “For instance, a potential explanation for both the price and utilization shifts might be if payer mix shifted toward more commercially insured patients at the expense of Medicaid or Medicare patients,” she wrote.

Zhu added that the impact of PE on prices and spending, by now replicated across different settings and specialties, is far clearer than the effect of PE on access and quality. “The analysis by Arnold et al is a welcome addition to the literature, generating important questions for future study and transparent monitoring as investor-owners become increasingly influential in healthcare.”

Going forward, said Gupta, an open question is whether the harmful effects of PE ownership of practices are differentially worse than those of other corporate entities such as insurers and hospital systems.

“There are reasons to believe that PE could be worse in theory. For example, their short-term investment horizon may force them to take measures that others will not as well as avoid investing into capital improvements that have a long-run payoff,” he said. “Their uniquely high dependence on debt and unbundling of real estate can severely hurt financial solvency of providers.” But high-quality evidence is lacking to compare the effects from these two distinct forms of corporatization.

The trend away from individual private practice is a reality, Arnold said. “The administrative burden on solo docs is becoming too much and physicians just seem to want to treat patients and not deal with it. So the options at this point really become selling to a hospital system or private equity.”

This study was funded by a grant from the philanthropic foundation Arnold Ventures (no family relation to Daniel Arnold). 

Arnold reported receiving grants from Arnold Ventures during the conduct of the study. Gupta had no competing interests to declare. Zhu reported receiving grants from the Agency for Healthcare Research and Quality during the submitted work and from the National Institutes of Health, National Institute for Health Care Management Foundation, and American Psychological Association, as well as personal fees from Cambia outside the submitted work.

A version of this article appeared on Medscape.com.

Private equity (PE) acquisition of gastroenterology (GI) practices led to higher colonoscopy prices, utilization, and spending with no commensurate effect on quality, an economic analysis found. Price increases ranged from about 5% to about 7%.

In view of the growing trend to such acquisitions, policy makers should monitor the impact of PE investment in medical practices, according to researchers led by health economist Daniel R. Arnold, PhD, of the Department of Health Services, Policy & Practice in the School of Public Health at Brown University in Providence, Rhode Island. “In a previous study of ours, gastroenterology stood out as a particularly attractive specialty to private equity,” Arnold told GI & Hepatology News.

Published in JAMA Health Forum, the economic evaluation of more than 1.1 million patients and 1.3 million colonoscopies concluded that PE acquisitions of GI sites are difficult to justify.

 

The Study

This difference-in-differences event study and economic evaluation analyzed data from US GI practices acquired by PE firms from 2015 to 2021. Commercial insurance claims covering more than 50 million enrollees were used to calculate price, spending, utilization, and quality measures from 2012 to 2021, with all data analyzed from April to September 2024.

The main outcomes were price, spending per physician, number of colonoscopies per physician, number of unique patients per physician, and quality, as defined by polyp detection, incomplete colonoscopies, and four adverse event measures: cardiovascular, serious and nonserious GI events, and any other adverse events.

The mean age of patients was 47.1 years, and 47.8% were men. The sample included 718, 851 colonoscopies conducted by 1494 physicians in 590, 900 patients across 1240 PE-acquired practice sites and 637, 990 control colonoscopies conducted by 2550 physicians in 527,380 patients across 2657 independent practice sites.

Among the findings:

• Colonoscopy prices at PE-acquired sites increased by 4.5% (95% CI, 2.5-6.6; P < .001) vs independent practices. That increase was much lower than that reported by Singh and colleagues for  .
• The estimated price increase was 6.7% (95% CI, 4.2-9.3; P < .001) when only colonoscopies at PE practices with market shares above the 75th percentile (24.4%) in 2021 were considered. Both increases were in line with other research, Arnold said.
• Colonoscopy spending per physician increased by 16.0% (95% CI, 8.4%-24.0%; P < .001), while the number of colonoscopies and the number of unique patients per physician increased by 12.1% (95% CI, 5.3-19.4; P < .001) and 11.3% (95% CI, 4.4%-18.5%; P < .001), respectively. These measures, however, were already increasing before PE acquisition.
• No statistically significant associations were detected for the six quality measures analyzed.

Could such cost-raising acquisitions potentially be blocked by concerned regulators? 

“No. Generally the purchases are at prices below what would require notification to federal authorities,” Arnold said. “The Department of Justice/Federal Trade Commission hinted at being willing to look at serial acquisitions in their 2023 Merger Guidelines, but until that happens, these will likely continue to fly under the radar.”

Still, as evidence of PE-associated poorer quality outcomes as well as clinician burnout continues to emerge, Arnold added, “I would advise physicians who get buyout offers from PE to educate themselves on what could happen to patients and staff if they choose to sell.”

Offering an outsider’s perspective on the study, health economist Atul Gupta, PhD, an assistant professor of healthcare management in the Wharton School at the University of Pennsylvania in Philadelphia, called it an “excellent addition to the developing literature examining the effects of private equity ownership of healthcare providers.” Very few studies have examined the effects on prices and quality for the same set of deals and providers. “This is important because we want to be able to do an apples-to-apples comparison of the effects on both outcomes before judging PE ownership,” he told GI & Hepatology News.

In an accompanying editorial , primary care physician Jane M. Zhu, MD, an associate professor of medicine at Oregon Health & Science University in Portland, Oregon, and not involved in the commercial-insurance-based study, said one interpretation of the findings may be that PE acquisition focuses on reducing inefficiencies, improving access by expanding practice capacity, and increasing throughput. “Another interpretation may be that PE acquisition is focused on the strategic exploitation of market and pricing power. The latter may have less of an impact on clinical measures like quality of care, but potentially, both strategies could be at play.” 

Since this analysis focused on the commercial population, understanding how patient demographics may change after PE acquisition is a future avenue for exploration. “For instance, a potential explanation for both the price and utilization shifts might be if payer mix shifted toward more commercially insured patients at the expense of Medicaid or Medicare patients,” she wrote.

Zhu added that the impact of PE on prices and spending, by now replicated across different settings and specialties, is far clearer than the effect of PE on access and quality. “The analysis by Arnold et al is a welcome addition to the literature, generating important questions for future study and transparent monitoring as investor-owners become increasingly influential in healthcare.”

Going forward, said Gupta, an open question is whether the harmful effects of PE ownership of practices are differentially worse than those of other corporate entities such as insurers and hospital systems.

“There are reasons to believe that PE could be worse in theory. For example, their short-term investment horizon may force them to take measures that others will not as well as avoid investing into capital improvements that have a long-run payoff,” he said. “Their uniquely high dependence on debt and unbundling of real estate can severely hurt financial solvency of providers.” But high-quality evidence is lacking to compare the effects from these two distinct forms of corporatization.

The trend away from individual private practice is a reality, Arnold said. “The administrative burden on solo docs is becoming too much and physicians just seem to want to treat patients and not deal with it. So the options at this point really become selling to a hospital system or private equity.”

This study was funded by a grant from the philanthropic foundation Arnold Ventures (no family relation to Daniel Arnold). 

Arnold reported receiving grants from Arnold Ventures during the conduct of the study. Gupta had no competing interests to declare. Zhu reported receiving grants from the Agency for Healthcare Research and Quality during the submitted work and from the National Institutes of Health, National Institute for Health Care Management Foundation, and American Psychological Association, as well as personal fees from Cambia outside the submitted work.

A version of this article appeared on Medscape.com.

WASHINGTON — For years, oncologist Jonathan Peled, MD, PhD, and his colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City have been documenting gut microbiota disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its role in frequent and potentially fatal bloodstream infections (BSIs) in the first 100 days after transplant.

Modulating microbiome composition to improve outcomes after allo-HSCT for hematological malignancies is a prime goal, and at the Gut Microbiota for Health (GMFH) World Summit 2025, Peled shared two new findings.

In one study, his team found that sucrose can exacerbate antibiotic-induced microbiome injury in patients undergoing allo-HSCT — a finding that “raises the question of whether our dietary recommendations [for] allo-HSCT patients are correct,” said Peled, assistant attending at MSKCC, during a session on the gut microbiome and oncology.

And in another study, they found that a rationally designed probiotic formulation may help lower the incidence of bacterial BSIs. In December 2024, the probiotic formulation (SER-155, Seres Therapeutics, Inc.) was granted breakthrough therapy designation by the FDA.

With immunotherapies more broadly, researchers are increasingly looking at diet and modulation of the microbiome to improve both treatment tolerance and efficacy, experts said at the meeting convened by the AGA and the European Society of Neurogastroenterology and Motility.

“Cancer patients and caregivers are asking, ‘What should I eat?’” said Carrie Daniel-MacDougall, PhD, MPH, a nutritional epidemiologist at the University of Texas MD Anderson Cancer Center in Houston. “They’re not just focused on side effects — they want a good outcome for their treatment, and they’re exploring a lot of dietary strategies [for which there] is not a lot of evidence.”

Clinicians are challenged by the fact that “we don’t typically collect dietary data in clinical trials of cancer drugs,” leaving them to extrapolate from evidence-based diet guidelines for cancer prevention, Daniel-MacDougall said.

But “I think that’s starting to shift,” she said, with the microbiome being increasingly recognized for its potential influences on therapeutic response and clinical trials underway looking at “a healthy dietary pattern not just for prevention but survival.”

 

Diet and Probiotics After allo-HSCT

The patterns of microbiota disruption during allo-HSCT — a procedure that includes antibiotic administration, chemotherapy, and sometimes irradiation — are characterized by loss of diversity and the expansion of potentially pathogenic organisms, most commonly Enterococcus, said Peled.

This has been demonstrated across transplantation centers. In a multicenter, international study published in 2020, the patterns of microbiota disruption and their impact on mortality were similar across MSK and other transplantation centers, with higher diversity of intestinal microbiota associated with lower mortality.

Other studies have shown that Enterococcus domination alone (defined arbitrarily as > 30% of fecal microbial composition) is associated with graft vs host disease and higher mortality after allo-HSCT and that intestinal domination by Proteobacteria coincides temporally with BSIs, he said.

Autologous fecal microbiota transplantation (FMT) has been shown to largely restore the microbiota composition the patient had before antibiotic treatment and allo-HSCT, he said, making fecal sample banking and posttreatment FMT a potential approach for reconstituting the gut microbiome and improving outcomes.

But “lately we’ve been very interested in diet for modulating [harmful] patterns” in the microbiome composition, Peled said.

In the new study suggesting a role for sugar avoidance, published last year as a bioRxiv preprint, Peled and his colleagues collected real-time dietary intake data (40,702 food entries) from 173 patients hospitalized for several weeks for allo-HSCT at MSK and analyzed it alongside longitudinally collected fecal samples. They used a Bayesian mixed-effects model to identify dietary components that may correlate with microbial disruption.

“What jumped out as very predictive of a low diversity fecal sample [and expansion of Enterococcus] in the 2 days prior to collection was the interaction between antibiotics and the consumption of sweets” — foods rich in simple sugars, Peled said. The relationship between sugar and the microbiome occurred only during periods of antibiotic exposure.

“And it was particularly perplexing because the foods that fall into the ‘sweets’ category are foods we encourage people to eat clinically when they’re not feeling well and food intake drops dramatically,” he said. This includes foods like nutritional drinks or shakes, Italian ice, gelatin dessert, and sports drinks.

(In a mouse model of post-antibiotic Enterococcus expansion, Peled and his co-investigators then validated the findings and ruled out the impact of any reductions in fiber.)

In addition to possibly revising dietary recommendations for patients undergoing allo-HSCT, the findings raise the question of whether avoiding sugar intake while on antibiotics, in general, is a way to mitigate antibiotic-induced dysbiosis, he said.

To test the role of probiotics, Peled and colleagues collaborated with Seres Therapeutics on a phase 1b trial of an oral combination (SER-155) of 16 fermented strains “selected rationally,” he said, for their ability to decolonize gut pathogens, improve gut barrier function (in vitro), and reduce gut inflammation and local immune activation.

After a safety lead-in, patients were randomized to receive SER-155 (20) or placebo (14) three times — prior to transplant, upon neutrophil engraftment (with vancomycin “conditioning”), and after transplant. “The strains succeeded in grafting in the [gastrointestinal] GI tract…and some of them persisted all the way through to day 100,” Peled said.

The incidence of pathogen domination was substantially lower in the probiotic recipients compared to an MSK historical control cohort, and the incidence of BSIs was significantly lower compared to the placebo arm (10% vs 43%, respectively, representing a 77% relative risk reduction), he said.

 

Diet and Immunotherapy Response: Trials at MD Anderson

One of the first trials Daniel-MacDougall launched at MD Anderson on diet and the microbiome randomized 55 patients who were obese and had a history of colorectal cancer or precancerous polyps to add a cup of beans to their usual diet or to continue their usual diet without beans. There was a crossover at 8 weeks in the 16-week BE GONE trial; stool and fasting blood were collected every 4 weeks.

“Beans are a prebiotic super-house in my opinion, and they’re also something this population would avoid,” said Daniel-MacDougall, associate professor in the department of epidemiology at MD Anderson and faculty director of the Bionutrition Research Core and Research Kitchen.

“We saw a modest increase in alpha diversity [in the intervention group] and similar trends with microbiota-derived metabolites” that regressed when patients returned to their usual diet, she said. The researchers also documented decreases in proteomic biomarkers of intestinal and systemic immune and inflammatory response.

The impact of diet on cancer survival was shown in subsequent research, including an observational study published in Science in 2021 of patients with melanoma receiving immune checkpoint blockade (ICB) treatment. “Patients who consumed insufficient dietary fiber at the start of therapy tended to do worse [than those reporting sufficient fiber intake],” with significantly lower progression-free survival, Daniel-MacDougall said.

“And interestingly, when we looked at dietary fiber [with and without] probiotic use, patients who had sufficient fiber but did not take probiotics did the best,” she said. [The probiotics were not endorsed or selected by their physicians.]

Now, the researchers at MD Anderson are moving into “precision nutrition” research, Daniel-MacDougall said, with a phase 2 randomized, double-blind trial of high dietary fiber intake (a target of 50 g/d from whole foods) vs a healthy control diet (20 g/d of fiber) in patients with melanoma receiving ICB.

The study, which is underway, is a fully controlled feeding study, with all meals and snacks provided by MD Anderson and macronutrients controlled. Researchers are collecting blood, stool, and tumor tissue (if available) to answer questions about the microbiome, changes in systemic and tissue immunity, disease response and immunotherapy toxicity, and other issues.

Peled disclosed IP licensing and research support from Seres Therapeutics; consulting with Da Volterra, MaaT Pharma, and CSL Behring; and advisory/equity with Postbiotics + Research LLC and Prodigy Biosciences. Daniel-MacDougall reported having no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — For years, oncologist Jonathan Peled, MD, PhD, and his colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City have been documenting gut microbiota disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its role in frequent and potentially fatal bloodstream infections (BSIs) in the first 100 days after transplant.

Modulating microbiome composition to improve outcomes after allo-HSCT for hematological malignancies is a prime goal, and at the Gut Microbiota for Health (GMFH) World Summit 2025, Peled shared two new findings.

In one study, his team found that sucrose can exacerbate antibiotic-induced microbiome injury in patients undergoing allo-HSCT — a finding that “raises the question of whether our dietary recommendations [for] allo-HSCT patients are correct,” said Peled, assistant attending at MSKCC, during a session on the gut microbiome and oncology.

And in another study, they found that a rationally designed probiotic formulation may help lower the incidence of bacterial BSIs. In December 2024, the probiotic formulation (SER-155, Seres Therapeutics, Inc.) was granted breakthrough therapy designation by the FDA.

With immunotherapies more broadly, researchers are increasingly looking at diet and modulation of the microbiome to improve both treatment tolerance and efficacy, experts said at the meeting convened by the AGA and the European Society of Neurogastroenterology and Motility.

“Cancer patients and caregivers are asking, ‘What should I eat?’” said Carrie Daniel-MacDougall, PhD, MPH, a nutritional epidemiologist at the University of Texas MD Anderson Cancer Center in Houston. “They’re not just focused on side effects — they want a good outcome for their treatment, and they’re exploring a lot of dietary strategies [for which there] is not a lot of evidence.”

Clinicians are challenged by the fact that “we don’t typically collect dietary data in clinical trials of cancer drugs,” leaving them to extrapolate from evidence-based diet guidelines for cancer prevention, Daniel-MacDougall said.

But “I think that’s starting to shift,” she said, with the microbiome being increasingly recognized for its potential influences on therapeutic response and clinical trials underway looking at “a healthy dietary pattern not just for prevention but survival.”

 

Diet and Probiotics After allo-HSCT

The patterns of microbiota disruption during allo-HSCT — a procedure that includes antibiotic administration, chemotherapy, and sometimes irradiation — are characterized by loss of diversity and the expansion of potentially pathogenic organisms, most commonly Enterococcus, said Peled.

This has been demonstrated across transplantation centers. In a multicenter, international study published in 2020, the patterns of microbiota disruption and their impact on mortality were similar across MSK and other transplantation centers, with higher diversity of intestinal microbiota associated with lower mortality.

Other studies have shown that Enterococcus domination alone (defined arbitrarily as > 30% of fecal microbial composition) is associated with graft vs host disease and higher mortality after allo-HSCT and that intestinal domination by Proteobacteria coincides temporally with BSIs, he said.

Autologous fecal microbiota transplantation (FMT) has been shown to largely restore the microbiota composition the patient had before antibiotic treatment and allo-HSCT, he said, making fecal sample banking and posttreatment FMT a potential approach for reconstituting the gut microbiome and improving outcomes.

But “lately we’ve been very interested in diet for modulating [harmful] patterns” in the microbiome composition, Peled said.

In the new study suggesting a role for sugar avoidance, published last year as a bioRxiv preprint, Peled and his colleagues collected real-time dietary intake data (40,702 food entries) from 173 patients hospitalized for several weeks for allo-HSCT at MSK and analyzed it alongside longitudinally collected fecal samples. They used a Bayesian mixed-effects model to identify dietary components that may correlate with microbial disruption.

“What jumped out as very predictive of a low diversity fecal sample [and expansion of Enterococcus] in the 2 days prior to collection was the interaction between antibiotics and the consumption of sweets” — foods rich in simple sugars, Peled said. The relationship between sugar and the microbiome occurred only during periods of antibiotic exposure.

“And it was particularly perplexing because the foods that fall into the ‘sweets’ category are foods we encourage people to eat clinically when they’re not feeling well and food intake drops dramatically,” he said. This includes foods like nutritional drinks or shakes, Italian ice, gelatin dessert, and sports drinks.

(In a mouse model of post-antibiotic Enterococcus expansion, Peled and his co-investigators then validated the findings and ruled out the impact of any reductions in fiber.)

In addition to possibly revising dietary recommendations for patients undergoing allo-HSCT, the findings raise the question of whether avoiding sugar intake while on antibiotics, in general, is a way to mitigate antibiotic-induced dysbiosis, he said.

To test the role of probiotics, Peled and colleagues collaborated with Seres Therapeutics on a phase 1b trial of an oral combination (SER-155) of 16 fermented strains “selected rationally,” he said, for their ability to decolonize gut pathogens, improve gut barrier function (in vitro), and reduce gut inflammation and local immune activation.

After a safety lead-in, patients were randomized to receive SER-155 (20) or placebo (14) three times — prior to transplant, upon neutrophil engraftment (with vancomycin “conditioning”), and after transplant. “The strains succeeded in grafting in the [gastrointestinal] GI tract…and some of them persisted all the way through to day 100,” Peled said.

The incidence of pathogen domination was substantially lower in the probiotic recipients compared to an MSK historical control cohort, and the incidence of BSIs was significantly lower compared to the placebo arm (10% vs 43%, respectively, representing a 77% relative risk reduction), he said.

 

Diet and Immunotherapy Response: Trials at MD Anderson

One of the first trials Daniel-MacDougall launched at MD Anderson on diet and the microbiome randomized 55 patients who were obese and had a history of colorectal cancer or precancerous polyps to add a cup of beans to their usual diet or to continue their usual diet without beans. There was a crossover at 8 weeks in the 16-week BE GONE trial; stool and fasting blood were collected every 4 weeks.

“Beans are a prebiotic super-house in my opinion, and they’re also something this population would avoid,” said Daniel-MacDougall, associate professor in the department of epidemiology at MD Anderson and faculty director of the Bionutrition Research Core and Research Kitchen.

“We saw a modest increase in alpha diversity [in the intervention group] and similar trends with microbiota-derived metabolites” that regressed when patients returned to their usual diet, she said. The researchers also documented decreases in proteomic biomarkers of intestinal and systemic immune and inflammatory response.

The impact of diet on cancer survival was shown in subsequent research, including an observational study published in Science in 2021 of patients with melanoma receiving immune checkpoint blockade (ICB) treatment. “Patients who consumed insufficient dietary fiber at the start of therapy tended to do worse [than those reporting sufficient fiber intake],” with significantly lower progression-free survival, Daniel-MacDougall said.

“And interestingly, when we looked at dietary fiber [with and without] probiotic use, patients who had sufficient fiber but did not take probiotics did the best,” she said. [The probiotics were not endorsed or selected by their physicians.]

Now, the researchers at MD Anderson are moving into “precision nutrition” research, Daniel-MacDougall said, with a phase 2 randomized, double-blind trial of high dietary fiber intake (a target of 50 g/d from whole foods) vs a healthy control diet (20 g/d of fiber) in patients with melanoma receiving ICB.

The study, which is underway, is a fully controlled feeding study, with all meals and snacks provided by MD Anderson and macronutrients controlled. Researchers are collecting blood, stool, and tumor tissue (if available) to answer questions about the microbiome, changes in systemic and tissue immunity, disease response and immunotherapy toxicity, and other issues.

Peled disclosed IP licensing and research support from Seres Therapeutics; consulting with Da Volterra, MaaT Pharma, and CSL Behring; and advisory/equity with Postbiotics + Research LLC and Prodigy Biosciences. Daniel-MacDougall reported having no disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — For years, oncologist Jonathan Peled, MD, PhD, and his colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City have been documenting gut microbiota disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its role in frequent and potentially fatal bloodstream infections (BSIs) in the first 100 days after transplant.

Modulating microbiome composition to improve outcomes after allo-HSCT for hematological malignancies is a prime goal, and at the Gut Microbiota for Health (GMFH) World Summit 2025, Peled shared two new findings.

In one study, his team found that sucrose can exacerbate antibiotic-induced microbiome injury in patients undergoing allo-HSCT — a finding that “raises the question of whether our dietary recommendations [for] allo-HSCT patients are correct,” said Peled, assistant attending at MSKCC, during a session on the gut microbiome and oncology.

And in another study, they found that a rationally designed probiotic formulation may help lower the incidence of bacterial BSIs. In December 2024, the probiotic formulation (SER-155, Seres Therapeutics, Inc.) was granted breakthrough therapy designation by the FDA.

With immunotherapies more broadly, researchers are increasingly looking at diet and modulation of the microbiome to improve both treatment tolerance and efficacy, experts said at the meeting convened by the AGA and the European Society of Neurogastroenterology and Motility.

“Cancer patients and caregivers are asking, ‘What should I eat?’” said Carrie Daniel-MacDougall, PhD, MPH, a nutritional epidemiologist at the University of Texas MD Anderson Cancer Center in Houston. “They’re not just focused on side effects — they want a good outcome for their treatment, and they’re exploring a lot of dietary strategies [for which there] is not a lot of evidence.”

Clinicians are challenged by the fact that “we don’t typically collect dietary data in clinical trials of cancer drugs,” leaving them to extrapolate from evidence-based diet guidelines for cancer prevention, Daniel-MacDougall said.

But “I think that’s starting to shift,” she said, with the microbiome being increasingly recognized for its potential influences on therapeutic response and clinical trials underway looking at “a healthy dietary pattern not just for prevention but survival.”

 

Diet and Probiotics After allo-HSCT

The patterns of microbiota disruption during allo-HSCT — a procedure that includes antibiotic administration, chemotherapy, and sometimes irradiation — are characterized by loss of diversity and the expansion of potentially pathogenic organisms, most commonly Enterococcus, said Peled.

This has been demonstrated across transplantation centers. In a multicenter, international study published in 2020, the patterns of microbiota disruption and their impact on mortality were similar across MSK and other transplantation centers, with higher diversity of intestinal microbiota associated with lower mortality.

Other studies have shown that Enterococcus domination alone (defined arbitrarily as > 30% of fecal microbial composition) is associated with graft vs host disease and higher mortality after allo-HSCT and that intestinal domination by Proteobacteria coincides temporally with BSIs, he said.

Autologous fecal microbiota transplantation (FMT) has been shown to largely restore the microbiota composition the patient had before antibiotic treatment and allo-HSCT, he said, making fecal sample banking and posttreatment FMT a potential approach for reconstituting the gut microbiome and improving outcomes.

But “lately we’ve been very interested in diet for modulating [harmful] patterns” in the microbiome composition, Peled said.

In the new study suggesting a role for sugar avoidance, published last year as a bioRxiv preprint, Peled and his colleagues collected real-time dietary intake data (40,702 food entries) from 173 patients hospitalized for several weeks for allo-HSCT at MSK and analyzed it alongside longitudinally collected fecal samples. They used a Bayesian mixed-effects model to identify dietary components that may correlate with microbial disruption.

“What jumped out as very predictive of a low diversity fecal sample [and expansion of Enterococcus] in the 2 days prior to collection was the interaction between antibiotics and the consumption of sweets” — foods rich in simple sugars, Peled said. The relationship between sugar and the microbiome occurred only during periods of antibiotic exposure.

“And it was particularly perplexing because the foods that fall into the ‘sweets’ category are foods we encourage people to eat clinically when they’re not feeling well and food intake drops dramatically,” he said. This includes foods like nutritional drinks or shakes, Italian ice, gelatin dessert, and sports drinks.

(In a mouse model of post-antibiotic Enterococcus expansion, Peled and his co-investigators then validated the findings and ruled out the impact of any reductions in fiber.)

In addition to possibly revising dietary recommendations for patients undergoing allo-HSCT, the findings raise the question of whether avoiding sugar intake while on antibiotics, in general, is a way to mitigate antibiotic-induced dysbiosis, he said.

To test the role of probiotics, Peled and colleagues collaborated with Seres Therapeutics on a phase 1b trial of an oral combination (SER-155) of 16 fermented strains “selected rationally,” he said, for their ability to decolonize gut pathogens, improve gut barrier function (in vitro), and reduce gut inflammation and local immune activation.

After a safety lead-in, patients were randomized to receive SER-155 (20) or placebo (14) three times — prior to transplant, upon neutrophil engraftment (with vancomycin “conditioning”), and after transplant. “The strains succeeded in grafting in the [gastrointestinal] GI tract…and some of them persisted all the way through to day 100,” Peled said.

The incidence of pathogen domination was substantially lower in the probiotic recipients compared to an MSK historical control cohort, and the incidence of BSIs was significantly lower compared to the placebo arm (10% vs 43%, respectively, representing a 77% relative risk reduction), he said.

 

Diet and Immunotherapy Response: Trials at MD Anderson

One of the first trials Daniel-MacDougall launched at MD Anderson on diet and the microbiome randomized 55 patients who were obese and had a history of colorectal cancer or precancerous polyps to add a cup of beans to their usual diet or to continue their usual diet without beans. There was a crossover at 8 weeks in the 16-week BE GONE trial; stool and fasting blood were collected every 4 weeks.

“Beans are a prebiotic super-house in my opinion, and they’re also something this population would avoid,” said Daniel-MacDougall, associate professor in the department of epidemiology at MD Anderson and faculty director of the Bionutrition Research Core and Research Kitchen.

“We saw a modest increase in alpha diversity [in the intervention group] and similar trends with microbiota-derived metabolites” that regressed when patients returned to their usual diet, she said. The researchers also documented decreases in proteomic biomarkers of intestinal and systemic immune and inflammatory response.

The impact of diet on cancer survival was shown in subsequent research, including an observational study published in Science in 2021 of patients with melanoma receiving immune checkpoint blockade (ICB) treatment. “Patients who consumed insufficient dietary fiber at the start of therapy tended to do worse [than those reporting sufficient fiber intake],” with significantly lower progression-free survival, Daniel-MacDougall said.

“And interestingly, when we looked at dietary fiber [with and without] probiotic use, patients who had sufficient fiber but did not take probiotics did the best,” she said. [The probiotics were not endorsed or selected by their physicians.]

Now, the researchers at MD Anderson are moving into “precision nutrition” research, Daniel-MacDougall said, with a phase 2 randomized, double-blind trial of high dietary fiber intake (a target of 50 g/d from whole foods) vs a healthy control diet (20 g/d of fiber) in patients with melanoma receiving ICB.

The study, which is underway, is a fully controlled feeding study, with all meals and snacks provided by MD Anderson and macronutrients controlled. Researchers are collecting blood, stool, and tumor tissue (if available) to answer questions about the microbiome, changes in systemic and tissue immunity, disease response and immunotherapy toxicity, and other issues.

Peled disclosed IP licensing and research support from Seres Therapeutics; consulting with Da Volterra, MaaT Pharma, and CSL Behring; and advisory/equity with Postbiotics + Research LLC and Prodigy Biosciences. Daniel-MacDougall reported having no disclosures.

A version of this article appeared on Medscape.com.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), the leading causes of liver disease, are now emerging as the main risk factors globally for primary liver cancer (PLC). Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.

A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.

The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.

The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.

“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”

Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.

Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.

Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.

MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.

By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”

Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.

“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”

Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), the leading causes of liver disease, are now emerging as the main risk factors globally for primary liver cancer (PLC). Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.

A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.

The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.

The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.

“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”

Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.

Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.

Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.

MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.

By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”

Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.

“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”

Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), the leading causes of liver disease, are now emerging as the main risk factors globally for primary liver cancer (PLC). Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.

A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.

The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.

The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.

“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”

Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.

Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.

Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.

MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.

By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”

Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.

“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”

Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.

Screening colonoscopies in 45- to 49-year-olds yield similar rates of cancer and lesions as in 50- to 54-year-olds, according to a new analysis.

Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.

The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.

The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma. 

About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.

There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.

Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.

The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.

Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.

The Kaiser research is “really powerful information,” she said.

“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.

The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.

Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.

But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.

Patel said that estimate is “spot on” in terms of other estimates. 

“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.

Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.

Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.

Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.

Calderwood and Patel reported having no relevant financial relationships.

A version of this article appeared on Medscape.com. 

Screening colonoscopies in 45- to 49-year-olds yield similar rates of cancer and lesions as in 50- to 54-year-olds, according to a new analysis.

Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.

The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.

The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma. 

About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.

There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.

Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.

The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.

Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.

The Kaiser research is “really powerful information,” she said.

“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.

The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.

Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.

But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.

Patel said that estimate is “spot on” in terms of other estimates. 

“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.

Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.

Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.

Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.

Calderwood and Patel reported having no relevant financial relationships.

A version of this article appeared on Medscape.com. 

Screening colonoscopies in 45- to 49-year-olds yield similar rates of cancer and lesions as in 50- to 54-year-olds, according to a new analysis.

Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.

The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.

The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma. 

About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.

There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.

Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.

The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.

Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.

The Kaiser research is “really powerful information,” she said.

“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.

The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.

Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.

But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.

Patel said that estimate is “spot on” in terms of other estimates. 

“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.

Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.

Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.

Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.

Calderwood and Patel reported having no relevant financial relationships.

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.

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.