Megan Brooks

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Colorectal cancer (CRC) in the United States continues to move in two different directions — decreasing in older adults and rising in younger adults, especially in those aged 20-49 years, according to the latest statistics from the American Cancer Society (ACS).

The ACS report, published online earlier this month, revealed that CRC incidence rates declined by 2.5% annually in adults aged ≥ 65 years but increased by 3% annually in adults aged 20-49 between 2013 and 2022 — higher than earlier estimates of 1% to 2% annual increases.

The trends are “concerning” and a “stark reminder that we’re seeing a shifting epidemiology,” said Folasade (Fola) May, MD, PhD, MPhil, director of the gastroenterology quality improvement program at UCLA Health in Los Angeles, who wasn’t involved in the analysis.

The report highlights the need for better education and symptom awareness — including bleeding, iron deficiency symptoms, and changes in bowel habits — among patients and doctors, who may not routinely consider cancer in younger adults, May explained.

“Because so many of the young people diagnosed present with advanced stage disease, early workup is critical to saving lives,” she said.

Rapidly Changing Landscape

In the United States, CRC is the third-most commonly diagnosed cancer in both men and women. CRC is also the second-leading cause of cancer-related deaths and the leading cause in adults aged < 50 years.

“After decades of progress, the risk of dying from colorectal cancer is climbing in younger generations of men and women, confirming a real uptick in disease because of something we’re doing or some other exposure,” Rebecca Siegel, MPH, senior scientific director of surveillance research at ACS and lead author of the report, said in a statement.

For the latest CRC statistics report, ACS scientists analyzed population-based registries, including the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, and mortality data from the CDC’s National Center for Health Statistics.

The report estimated that 158,850 new CRC cases will be diagnosed in the US in 2026, including 108,860 colon cancers and 49,990 rectal cancers; an estimated 55,230 people will die from the disease.

Overall, CRC incidence declined by 0.9% annually from 2013 to 2022, driven by decreases of 2.5% per year in adults aged ≥ 65 years. During the same period, however, incidence rates rose by about 3% per year in adults aged 20-49 years and by 0.4% per year in those aged 50-64 years. CRC mortality also continued to trend downward in adults aged ≥ 65 years by > 2% per year, but mortality increased by 1% per year in adults aged < 50 years since 2004 and in adults aged 50-64 years since 2019.

Nearly half of new CRC cases (45%) now occur in adults aged < 65 years, up from 27% in 1995, illustrating a major shift toward younger age groups, the authors said. Half of early-onset cases occur in people aged 45-49 years who are now eligible for screening, and 3 of 4 early-onset CRC cases are diagnosed at an advanced stage, including about 27% with distant metastases.

“This is partly because of less screening, but it also reflects diagnostic delays,” according to Siegel and coauthors, who noted data show screening uptake remains low in individuals aged 45-49 (37%) and 50-54 (55%) years. The incidence of early-onset CRC increased across all racial and ethnic groups in the US, from 2% annually in Black individuals to 4% annually in Hispanic individuals between 2013 and 2022.

Aside from early-onset trends, the analysis found that tumor location trends shifted as well. Rectal cancer incidence increased in all ages combined (by 1% per year from 2018 to 2022), reversing decades of decline and now accounting for nearly one third of all CRC, compared with 27% in the mid-2000s.

The report also indicated that racial and ethnic disparities persist. Alaska Native individuals had the highest CRC incidence (80.9 per 100,000) and mortality (31.5 per 100,000) in the US, more than twofold that of White patients (35.2 and 12.9 per 100,000, respectively). Asian American, Native Hawaiian, and other Pacific Islanders had the lowest incidence (28.5 per 100,000) and mortality rates (9.2 per 100,000).

Although cancer registries like SEER are not perfect, they are “the best data we have” and overall the SEER data “very reliably represent what is going on in the US population,” May said.

The latest findings also further underscore that CRC is “worsening among younger generations and highlight the immediate need for eligible adults to begin screening at the recommended age of 45,” William Dahut, MD, ACS chief scientific officer, said in the statement.

The study had no commercial funding. The authors and May reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

A version of this article first appeared on Medscape.com.

A trio of new studies, published simultaneously in February in Nature Medicine, add to growing evidence that manipulating the gut microbiome may enhance responses to immunotherapy in selected patients with cancer.

In these small, early-phase studies involving patients with metastatic renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and melanoma receiving immune checkpoint inhibitor (ICI) therapy, fecal microbiota transplantation (FMT) was associated with objective response rates that compared favorably with historical or prespecified benchmarks.

The idea that microbiome modulation via FMT “can augment immunotherapy efficacy is probably a good one and these studies certainly support that hypothesis,” said Diwakar Davar, MD, assistant professor of medicine and an oncologist/hematologist at the University of Pittsburgh, Pennsylvania, who wasn’t part of the new work.While “an intriguing approach and certainly worthy of further evaluation,” Davar cautioned that the latest studies are not robust enough to answer the question conclusively.

Although ICIs have improved outcomes for patients with melanoma, NSCLC, and RCC, many patients still do not respond or eventually develop resistance. A growing body of evidence suggests that the gut microbiome can influence the effectiveness of ICI therapy. However, much of this evidence comes from preclinical studies showing that modulating the microbiome via FMT can alter responses to immunotherapy, along with small proof-of-concept human studies — predominantly in melanoma — suggesting this approach may help overcome primary or acquired resistance to anti-PD-1 therapy.

The new studies aimed to build on this foundation by exploring whether FMT could improve ICI responses and clinical outcomes in patients with NSCLC, melanoma, and RCC.

In the phase 2, open-label FMT-LUMINate trial, researchers tested a healthy-donor FMT delivered as oral capsules before patients began immunotherapy. FMT capsules were produced using 80-100 g of feces per dose from screened healthy donors, and patients consumed 30-40 capsules while under supervision. The study included 20 patients with NSCLC and high PD-L1 tumor expression receiving FMT before standard first-line pembrolizumab monotherapy and 20 patients with cutaneous melanoma receiving FMT before ipilimumab plus nivolumab.

In the NSCLC cohort, 16 patients (80%) achieved an objective response. The 80% objective response rate exceeded the prespecified efficacy threshold of 64% and was higher than previously described historical data, which ranged from 39% to 46%, the study team noted.

In the melanoma cohort, FMT before nivolumab and ipilimumab yielded an objective response rate of 75%, also exceeding the historical expected response rates of 50% to 58% among patients receiving this ICI combination.

In patients with NSCLC, no grade 3 or higher adverse events were reported. However, grade 3 or higher adverse events were reported in 13 (65%) patients in the melanoma group, suggesting a potentially accelerated onset of immune-related adverse events. Researchers also observed a higher-than-expected frequency of myocarditis in melanoma patients (15%). These toxicities clustered among patients who had FMT donors enriched in Prevotella spp, highlighting the importance of donor selection for future trials, the researchers explained.

The team plans to assess the potential of FMT to overcome primary resistance to ICI as part of the phase 2 CanBiome2 randomized trial, which aims to enroll 128 patients.

The RCC Data

The other two studies focused on FMT in patients with metastatic RCC. In the phase 1 PERFORM study, 20 treatment-naive patients with metastatic RCC added encapsulated healthy-donor FMT to standard ICI-based regimens — most commonly ipilimumab plus nivolumab, with some patients receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib.

The primary endpoint was safety defined by the incidence and severity of immune-related adverse events. The safety endpoint was met; 50% of patients (10 of 20) experienced grade 3 immune-related adverse events, and there were no serious FMT-related toxicities and no grade 4 or 5 events.

Among 18 evaluable patients, nine (50%) achieved an objective response, including two who had complete responses (11%). Notably, most treatment responders did not develop any grade 3 or higher immune-related adverse events, the researchers reported.

Finally, in the phase 2a TACITO trial, 45 patients with treatment-naive metastatic RCC were randomly allocated to receive donor FMT or placebo FMT. Patients received three administrations over 6 months — first via colonoscopy then as capsulized doses, alongside pembrolizumab plus axitinib.

The primary endpoint of 12-month progression-free survival narrowly missed statistical significance — 70% vs 41% (P = .053) — but suggested a benefit in the donor FMT group.

“We need more than 1 year to appreciate statistical significance in terms of progression-free survival,” study investigator Gianluca Ianiro, MD, PhD, with Catholic University of the Sacred Heart, Rome, told Medscape Medical News.

As for secondary endpoints, median progression-free survival was significantly longer with donor FMT (24.0 vs 9.0 months; hazard ratio, 0.50; P = .035) and the objective response rate was higher with donor FMT (52% vs 32%).

Why Might FMT Boost ICI Response?

Conceptually, FMT is intended to reshape the gut ecosystem in ways that favor antitumor immunity, and possibly reduce immune dysregulation.

Across these new studies, the mechanistic story is moving beyond the idea that more diversity is good and toward a model that suggests a benefit to removing or suppressing taxa associated with resistance or inflammatory toxicity.

For example, in the TACITO trial, microbiome analysis confirmed that acquisition or loss of specific bacterial strains was associated with 12-month progression-free survival.

Additionally, results of the FMT-LUMINate trial hinted that the therapeutic benefit of FMT may be driven by eliminating harmful bacteria present at baseline, most notably Enterocloster, Clostridium and Streptococcus spp.

“This bacterial depletion was associated with a favorable immunometabolic milieu,” the FMT-LUMINate researchers wrote. Additionally, the results suggest that “failure to eliminate baseline deleterious taxa may sustain an immunosuppressive metabolic and systemic immune milieu that compromises ICI responses.”

Is FMT Ready for Prime Time?

Ianiro told Medscape Medical News he “definitely” thinks microbiome modulation could eventually become part of standard immunotherapy regimens.

Although the “signal” of benefit is clearly there, Davar cautioned that it’s too early to justify routine, off-trial use of FMT specifically to improve ICI response.

“These remain small, proof-of-concept studies. They are not adequately powered trials of fecal transplants and multiple different covariates haven’t been considered,” Davar said.

The study researchers noted that issues around donor selection and availability, dosing schedules, product standardization, and safety risk stratification need to be resolved.

For example, TACITO’s real-world experience shows logistics can matter. Delays occurred due to capsule unavailability and other scheduling barriers, which led to late dosing and missed or shifted treatments in some patients.

That’s a reminder that scaling FMT for oncology would require robust manufacturing, distribution, and time-sensitive coordination with ICI start dates.

More broadly, “whether FMT is the most suitable method of essentially changing the gut microbiome remains unclear,” explained Davar, who suggested that engineered microbiome therapeutics or tailored therapies may be a preferable, more scalable and tailored long-term solution.

Overall, does this new research provide impetus to develop stool banks? “Probably not,” Davar said.

But is it a call for interested parties to think about clinical trials and experimental products that could influence the gut microbiome? “Those are all probably good ideas,” he said.

The PERFORM, TACITO and FMT-LUMINate trials had no commercial funding. Saman Maleki Vareki, PhD, of the PERFORM trial, is a cofounder of LND Therapeutics Inc and has submitted a US patent application related to FMT donor screening. Ianiro has received personal fees for acting as a speaker for Biocodex and Illumina and for acting as a consultant/advisor for Ferring Therapeutics. Arielle Elkrief, MD, of the FMT-LUMINate trial, has received honoraria from AstraZeneca, Merck, Bristol Myers Squibb, and EMD Serono; consulting fees from EverImmune, NECBio, and Sanofi-Pasteur; and is an inventor on a patent regarding the microbiome and immunotherapy response. Davar had no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research challenges the assumption that long-term cannabis use improves symptoms or functioning in posttraumatic stress disorder (PTSD).

On the contrary, researchers found that abstaining from cannabis for 3 months was associated with significantly greater reductions in PTSD symptoms in adults with PTSD and comorbid cannabis use disorder (CUD).

The data suggest that continued cannabis use could limit recovery in some domains — underscoring the need to routinely assess cannabis use during PTSD treatment and to educate patients on the potential consequences of continued use, the researchers said. 

The study was published online February 18 in the Journal of Clinical Psychiatry. 

Helpful or Harmful? 

PTSD is a debilitating psychiatric condition marked by intrusive memories, avoidance, negative changes in mood and cognition, and hyperarousal. Many patients turn to cannabis to ease symptoms. In one recent study, roughly 28% of individuals with PTSD reported past-year cannabis use and 9% met criteria for CUD. 

Although some studies have suggested PTSD symptom reduction with cannabis or cannabinoid-based treatments, others have identified potential risks, such as disrupted fear-extinction learning and worse clinical and treatment outcomes. 

A recent systematic review found mixed evidence overall, with six studies suggesting benefits, five reporting worsening of symptoms, and three showing no significant impact of cannabis use in the setting of PTSD.

Led by Ahmed Hassan, MD, University of Toronto, Ontario, the researchers recruited adults aged 18-65 years with confirmed PTSD and CUD through the Centre for Addiction and Mental Health in Toronto and asked them to discontinue cannabis for 12 weeks.

Abstinence was defined as a urine 11-nor-9-carboxy-tetrahydrocannabinol level of 50 ng/mL or lower with no self-reported use, verified at multiple timepoints. Participants received escalating cash incentives for remaining abstinent at weeks 4, 8, and 12.

Eleven (52%) of the 21 participants who completed the 12-week protocol achieved biochemically verified abstinence, while 10 did not.

Those who achieved abstinence reported significantly greater reductions in total PTSD symptom severity and symptom count compared to those who did not. 

Total severity scores on the Clinician-Administered PTSD Scale for DSM-5 dropped from 36.2 at baseline to 10.5 at week 12 among abstainers vs 34.6 to 21.8 among those who did not maintain abstinence (P = .001).

A similar pattern emerged for total symptom count, with abstinent participants dropping from 14.3 symptoms at baseline to 4.1 at week 12, compared to a decrease from 13.5 to 8.9 among nonabstainers.

Notably, the investigators observed that individuals who remained abstinent showed greater reductions in several core symptom clusters, including avoidance, negative alterations in mood, cognition, and hyperarousal — domains that are often cited as targets for cannabis-based self-medication among individuals with PTSD. 

“However, in this comorbid PTSD and CUD sample, sustained cannabis abstinence was associated with symptom improvement, thereby challenging assumptions about its clinical utility in this population,” they wrote. 

Interestingly, they added that there were no differential effects on reexperiencing symptoms such as flashbacks, intrusive memories, and nightmares. Both abstinent and nonabstinent participants reported similar improvements in reexperiencing, suggesting that factors unrelated to cannabis use may have contributed to symptom change or insufficient power, the authors said. 

The researchers called for larger randomized trials to “replicate and extend” these preliminary findings and to investigate mechanisms through which abstinence may relate to symptom changes in PTSD with CUD.

The study had no commercial funding. The authors had no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research challenges the assumption that long-term cannabis use improves symptoms or functioning in posttraumatic stress disorder (PTSD).

On the contrary, researchers found that abstaining from cannabis for 3 months was associated with significantly greater reductions in PTSD symptoms in adults with PTSD and comorbid cannabis use disorder (CUD).

The data suggest that continued cannabis use could limit recovery in some domains — underscoring the need to routinely assess cannabis use during PTSD treatment and to educate patients on the potential consequences of continued use, the researchers said. 

The study was published online February 18 in the Journal of Clinical Psychiatry. 

Helpful or Harmful? 

PTSD is a debilitating psychiatric condition marked by intrusive memories, avoidance, negative changes in mood and cognition, and hyperarousal. Many patients turn to cannabis to ease symptoms. In one recent study, roughly 28% of individuals with PTSD reported past-year cannabis use and 9% met criteria for CUD. 

Although some studies have suggested PTSD symptom reduction with cannabis or cannabinoid-based treatments, others have identified potential risks, such as disrupted fear-extinction learning and worse clinical and treatment outcomes. 

A recent systematic review found mixed evidence overall, with six studies suggesting benefits, five reporting worsening of symptoms, and three showing no significant impact of cannabis use in the setting of PTSD.

Led by Ahmed Hassan, MD, University of Toronto, Ontario, the researchers recruited adults aged 18-65 years with confirmed PTSD and CUD through the Centre for Addiction and Mental Health in Toronto and asked them to discontinue cannabis for 12 weeks.

Abstinence was defined as a urine 11-nor-9-carboxy-tetrahydrocannabinol level of 50 ng/mL or lower with no self-reported use, verified at multiple timepoints. Participants received escalating cash incentives for remaining abstinent at weeks 4, 8, and 12.

Eleven (52%) of the 21 participants who completed the 12-week protocol achieved biochemically verified abstinence, while 10 did not.

Those who achieved abstinence reported significantly greater reductions in total PTSD symptom severity and symptom count compared to those who did not. 

Total severity scores on the Clinician-Administered PTSD Scale for DSM-5 dropped from 36.2 at baseline to 10.5 at week 12 among abstainers vs 34.6 to 21.8 among those who did not maintain abstinence (P = .001).

A similar pattern emerged for total symptom count, with abstinent participants dropping from 14.3 symptoms at baseline to 4.1 at week 12, compared to a decrease from 13.5 to 8.9 among nonabstainers.

Notably, the investigators observed that individuals who remained abstinent showed greater reductions in several core symptom clusters, including avoidance, negative alterations in mood, cognition, and hyperarousal — domains that are often cited as targets for cannabis-based self-medication among individuals with PTSD. 

“However, in this comorbid PTSD and CUD sample, sustained cannabis abstinence was associated with symptom improvement, thereby challenging assumptions about its clinical utility in this population,” they wrote. 

Interestingly, they added that there were no differential effects on reexperiencing symptoms such as flashbacks, intrusive memories, and nightmares. Both abstinent and nonabstinent participants reported similar improvements in reexperiencing, suggesting that factors unrelated to cannabis use may have contributed to symptom change or insufficient power, the authors said. 

The researchers called for larger randomized trials to “replicate and extend” these preliminary findings and to investigate mechanisms through which abstinence may relate to symptom changes in PTSD with CUD.

The study had no commercial funding. The authors had no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research challenges the assumption that long-term cannabis use improves symptoms or functioning in posttraumatic stress disorder (PTSD).

On the contrary, researchers found that abstaining from cannabis for 3 months was associated with significantly greater reductions in PTSD symptoms in adults with PTSD and comorbid cannabis use disorder (CUD).

The data suggest that continued cannabis use could limit recovery in some domains — underscoring the need to routinely assess cannabis use during PTSD treatment and to educate patients on the potential consequences of continued use, the researchers said. 

The study was published online February 18 in the Journal of Clinical Psychiatry. 

Helpful or Harmful? 

PTSD is a debilitating psychiatric condition marked by intrusive memories, avoidance, negative changes in mood and cognition, and hyperarousal. Many patients turn to cannabis to ease symptoms. In one recent study, roughly 28% of individuals with PTSD reported past-year cannabis use and 9% met criteria for CUD. 

Although some studies have suggested PTSD symptom reduction with cannabis or cannabinoid-based treatments, others have identified potential risks, such as disrupted fear-extinction learning and worse clinical and treatment outcomes. 

A recent systematic review found mixed evidence overall, with six studies suggesting benefits, five reporting worsening of symptoms, and three showing no significant impact of cannabis use in the setting of PTSD.

Led by Ahmed Hassan, MD, University of Toronto, Ontario, the researchers recruited adults aged 18-65 years with confirmed PTSD and CUD through the Centre for Addiction and Mental Health in Toronto and asked them to discontinue cannabis for 12 weeks.

Abstinence was defined as a urine 11-nor-9-carboxy-tetrahydrocannabinol level of 50 ng/mL or lower with no self-reported use, verified at multiple timepoints. Participants received escalating cash incentives for remaining abstinent at weeks 4, 8, and 12.

Eleven (52%) of the 21 participants who completed the 12-week protocol achieved biochemically verified abstinence, while 10 did not.

Those who achieved abstinence reported significantly greater reductions in total PTSD symptom severity and symptom count compared to those who did not. 

Total severity scores on the Clinician-Administered PTSD Scale for DSM-5 dropped from 36.2 at baseline to 10.5 at week 12 among abstainers vs 34.6 to 21.8 among those who did not maintain abstinence (P = .001).

A similar pattern emerged for total symptom count, with abstinent participants dropping from 14.3 symptoms at baseline to 4.1 at week 12, compared to a decrease from 13.5 to 8.9 among nonabstainers.

Notably, the investigators observed that individuals who remained abstinent showed greater reductions in several core symptom clusters, including avoidance, negative alterations in mood, cognition, and hyperarousal — domains that are often cited as targets for cannabis-based self-medication among individuals with PTSD. 

“However, in this comorbid PTSD and CUD sample, sustained cannabis abstinence was associated with symptom improvement, thereby challenging assumptions about its clinical utility in this population,” they wrote. 

Interestingly, they added that there were no differential effects on reexperiencing symptoms such as flashbacks, intrusive memories, and nightmares. Both abstinent and nonabstinent participants reported similar improvements in reexperiencing, suggesting that factors unrelated to cannabis use may have contributed to symptom change or insufficient power, the authors said. 

The researchers called for larger randomized trials to “replicate and extend” these preliminary findings and to investigate mechanisms through which abstinence may relate to symptom changes in PTSD with CUD.

The study had no commercial funding. The authors had no relevant disclosures.

A version of this article first appeared on Medscape.com.

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

The FDA has granted traditional approval to encorafenib (Braftovi, Pfizer) in combination with cetuximab (Erbitux, Eli Lilly) and fluorouracil-based chemotherapy for treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-authorized test.

Encorafenib received accelerated approval for use with cetuximab plus mFOLFOX6 in this patient population in 2024, based on results from the BREAKWATER trial showing improved objective response rates. The conversion to full approval is supported by progression-free and overall survival outcomes.

As reported previously by Medscape Medical News, the combination of encorafenib/cetuximab/mFOLFOX6 doubled median overall survival compared with standard chemotherapy with or without bevacizumab. At a median follow-up of 22 months, overall survival was 30 months with the encorafenib regimen vs 15 months with standard chemotherapy (hazard ratio [HR], 0.49; P < .0001).

At median follow up of 16.8 months, median progression-free survival was 12.8 in the encorafenib group vs 7.1 months in the standard chemotherapy group (HR, 0.53; P < .0001).

The survival results are “unprecedented” and “practice changing” for these patients, who historically have a poor prognosis, lead investigator Elena Élez, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, said in presenting the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.

The results were simultaneously published in The New England Journal of Medicine.

Speaking at the ASCO meeting, study discussant Andrea Sartore-Bianchi, MD, of the University of Milan, Italy, called the results “striking” and said the encorafenib combination should be considered the first-line standard of care.

As for safety, the rate of treatment-related grade 3/4 adverse events in the trial was 76% with encorafenib vs 59% with standard chemotherapy. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation.

The recommended encorafenib dose is 300 mg (four 75 mg capsules) once daily, in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity, the FDA said in its approval announcement.

Prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF-wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

A version of this article first appeared on Medscape.com.

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

New research sheds light on how chronic heavy alcohol use may contribute to colorectal cancer (CRC) development and how quitting may lower the risk for precancerous colorectal adenomas.

In a large US cancer screening trial, current heavy drinkers — with an average lifetime alcohol intake of 14 or more drinks per week — had a 25% higher risk for CRC and an almost twofold higher risk for rectal cancer than light drinkers averaging less than one drink per week.

When the research team further considered drinking consistency, steady heavy drinking throughout adulthood was associated with a 91% higher risk for CRC than consistent light drinking. 

Additionally, no increased risk for CRC was found among former drinkers, and former drinkers were less likely than light drinkers to develop nonadvanced colorectal adenomas.

This analysis “adds to the growing amount of concerning literature showing that chronic heavy alcohol use can potentially contribute to colorectal cancer development,” Benjamin H. Levy III, MD, gastroenterologist and clinical associate of medicine at UChicago Medicine in Chicago, who wasn’t involved in the study, told Medscape Medical News.

The study’s co-senior author, Erikka Loftfield, PhD, MPH, also noted that the study “provides new evidence indicating that drinking cessation, compared to consistent light drinking, may lower adenoma risk.”

Current cancer prevention guidelines recommend limiting alcohol intake or ideally not drinking at all, and “our findings do not change this advice,” said Loftfield, with the National Cancer Institute (NCI) in Bethesda, Maryland. 

The study was published online on January 26 in the journal Cancer.

Addressing a Data Gap

Alcoholic beverages are classified as carcinogenic to humans and are causally associated with CRC, Loftfield told Medscape Medical News. However, much of the evidence for this comes from cohort studies that only measure recent drinking patterns, generally among older adults, at study baseline. Fewer studies have looked at how drinking over a person’s lifetime and alcohol consumption patterns relate to colorectal adenoma and CRC risk, she explained.

To address these gaps, Loftfield and colleagues leveraged data on alcohol intake gathered as part of the NCI’s Prostate, Long, Colorectal, and Ovarian Cancer Screening Trial.

Average lifetime alcohol intake was calculated as drinks per week from age 18 through study baseline, and drinking patterns were further classified based on consistency and intensity over time. 

During 20 years of follow-up, 1679 incident CRC cases occurred among 88,092 study participants. In multivariable-adjusted analyses, current heavy drinkers had a higher risk for CRC than those averaging less than one drink per week (hazard ratio [HR], 1.25), with the strongest association observed for rectal cancer (HR, 1.95).

“The increase in rectal cancer risk for heavy drinkers seen in this 20-year observational study was especially concerning,” Levy told Medscape Medical News.

What About Moderate Drinking?

Perhaps counterintuitively, moderate current drinkers (those consuming an average of 7 to less than 14 drinks per week) had a lower risk for CRC (HR, 0.79), especially distal colon cancer (HR, 0.64), than light drinkers.

Loftfield said that research in rodents suggests moderate alcohol intake may reduce inflammation and lower DNA damage, but it’s possible that the observed inverse association is due to residual confounding by unmeasured or poorly measured confounders, such as socioeconomic status.

She said it’s also important to note that the inverse association of moderate alcohol intake was strongest for distal colon cancer and in the screening arm of the trial. Those in the screening arm who screened positive with flexible sigmoidoscopy had polyps removed and were referred for colonoscopy during the trial period, making screening a potential intervention as well.

“Screening with flexible sigmoidoscopy has previously been found to decrease CRC incidence, specifically distal colon cancer, in this population. Thus, it is possible that better adherence to screening among moderate drinkers over the course of follow-up contributed to this finding,” Loftfield explained.

When looking at consistency of drinking, her team found that current drinkers who were consistent heavy drinkers throughout adulthood had a higher risk for CRC than consistent light drinkers (HR, 1.91).

Separate analyses of incident colorectal adenomas were directionally consistent with the CRC findings. These analyses included 12,327 participants with a negative baseline sigmoidoscopy, among whom 812 adenomas were detected on repeat screening.

Compared with current light drinkers, former drinkers had significantly lower odds of nonadvanced adenomas (odds ratio [OR], 0.58), but no significant association was observed for advanced adenomas (OR, 1.08; 95% CI, 0.62-1.90). The authors cautioned, however, that overall adenoma case numbers were limited, and estimates for advanced lesions were imprecise.

Educating Patients

Reached for comment, William Dahut, chief scientific officer for the American Cancer Society, told Medscape Medical News that this “very well done, large perspective study clearly demonstrates the significant increased risk of colorectal cancer for those that are heavy drinkers.”

He noted that the nearly twofold increased risk for rectal cancer among heavy drinkers “makes biological sense because the rectum is the area of the body where the toxins produced by alcohol potentially spend the most period of time.” 

Heavy drinkers are at the highest risk, Dahut said, and “for them, screenings are particularly important.”

Even with this growing body of evidence, Levy noted that many patients in America and worldwide “have not been educated yet about the potential carcinogenic dangers of chronic alcohol use.”

Levy recommended that physicians get “accurate social histories about alcohol use” and “spend several minutes educating patients about their increased risk of cancer and liver problems from heavy alcohol use.”

Dahut encouraged health providers to tell patients that the risk for CRC from alcohol is also based on one’s lifetime alcohol consumption, “not simply what they had last weekend.”

Overall, this important research study, along with the Surgeon General’s recent publication about Alcohol and Cancer Risk, will hopefully “encourage physicians to have important conversations about alcohol reduction with their patients,” Levy said. 

The study had no commercial funding. Loftfield, Dahult, and Levy reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

A version of this article first appeared on Medscape.com.

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

A version of this article first appeared on Medscape.com.

The targeted therapy combination of encorafenib and cetuximab with FOLFIRI (leucovorin/5-fluorouracil [FU]/irinotecan) chemotherapy may be a new first-line option for patients with BRAF V600E-mutant metastatic colorectal cancer (CRC), according to new results from the BREAKWATER trial.

After a median follow-up of about 10 months, response rates were significantly better with encorafenib and cetuximab plus FOLFIRI than with FOLFIRI alone — without increasing side effects.

The findings, presented at the ASCO Gastrointestinal Cancers Symposium 2026, point to a potential new option for the 20%-25% of patients with BRAF V600E-mutant metastatic CRC who receive FOLFIRI as their chemotherapy.

Based on previous results from BREAKWATER, the FDA granted accelerated approval to first-line encorafenib (Braftovi) and cetuximab (Erbitux) plus mFOLFOX6 for this patient population. That regimen doubled median overall survival compared with standard chemotherapy with or without bevacizumab.

Cohort 3 of BREAKWATER was designed to address a specific question: Are the benefits with the targeted therapy duo a “FOLFOX-specific phenomenon?” lead investigator Scott Kopetz, MD, PhD, of MD Anderson Cancer Center, Houston, said during a press briefing.

Based on these early results, the answer is no. Instead, Kopetz said, there appears to be a “broader synergy” between the targeted therapies and cytotoxic chemotherapy.

Joel Saltzman, MD, ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic in Cleveland, agreed.

“The additional data from the BREAKWATER trial reveals that it is the targeted therapy backbone that provides the better disease control and response rate in BRAF V600E-mutant colorectal cancers,” he said.

BRAF V600E mutations occur in up to 12% of patients with metastatic CRC and are associated with poor outcomes. While many newly diagnosed patients receive FOLFOX (leucovorin/5-FU/oxaliplatin) in the first line, FOLFIRI is a common alternative — often due to concerns about oxaliplatin-associated peripheral neuropathy, Kopetz noted.

The safety lead-in portion of BREAKWATER showed that encorafenib and cetuximab plus FOLFIRI were tolerable and had promising antitumor activity.

Cohort 3 of the trial included 147 patients (mean age, 62 years; 46% male) with BRAF V600E-mutant metastatic CRC, no prior systemic treatment, and good performance status (Eastern Cooperative Oncology Group PS 0 or 1); 73 patients were randomly allocated to encorafenib and cetuximab plus FOLFIRI and 74 to FOLFIRI with or without bevacizumab. The primary endpoint was objective response rate assessed by blinded independent central review.

After a median follow-up of 10 months, patients in the targeted therapy group had an objective response rate of 64.4% vs 39.2% among patients who received FOLFIRI alone or with bevacizumab (odds ratio, 2.76; P = .001).

Responses to the targeted therapies were “rapid and durable,” Kopetz said. More than half (57.4%) of patients treated with encorafenib and cetuximab and FOLFIRI had a duration of response of 6 months or longer than 34.5% in the control group.

Data on overall survival, a secondary endpoint, were not yet mature, but there was a trend toward improved survival with targeted therapy.

Importantly, Kopetz reported, there were no new safety signals, and serious treatment-emergent adverse events occurred at a similar rate in both treatment groups: 39.4% in the targeted therapy group and 36.8% in the control group.

The most common adverse events in both groups included nausea, diarrhea, vomiting, fatigue, appetite loss, and alopecia. About 10% of patients in the targeted therapy group and 9% of those in the control group discontinued their treatment early, suggesting the severity of side effects was similar between the groups.

Kopetz cautioned that the data are still early and follow-up is ongoing. However, he said, the findings support the targeted drugs plus FOLFIRI as a “potential new standard of care” for this patient population.

“The addition of FOLFIRI chemotherapy in the frontline setting will give oncologists and patients more options when selecting a first-line regimen,” Saltzman said. “To have as many options as possible is certainly something we all hope for.”

The trial was funded by Pfizer. Kopetz reported consulting for Pfizer and several other pharmaceutical companies. Saltzman reported having no disclosures.

A version of this article first appeared on Medscape.com.

The GLP-1 drugs widely prescribed for diabetes and weight loss might also help reduce the risk for colorectal cancer and possibly improve outcomes in people who have the disease, according to a series of studies presented at ASCO Gastrointestinal Cancers Symposium 2026.

In one study, researchers observed a 36% lower risk for colorectal cancer among people who used GLP-1 receptor agonists vs those who used aspirin — a drug long investigated for colorectal cancer primary prevention.

While aspirin has shown “modest efficacy” in that regard, it also carries a bleeding risk that limits its use, Colton Jones, MD, a hematology and oncology fellow with The University of Texas San Antonio, told conference attendees.

Emerging evidence suggests that GLP-1s possess anti-inflammatory and anti-neoplastic properties, while some recent observational studies have linked the medications to reduced risks for certain cancers, particularly obesity-related types.

However, Jones said, research into a possible role for GLP-1s in cancer risk reduction is still in the early stages.

Prevention Potential

To conduct a “real-world” analysis, Jones and his colleagues turned to the TriNetX database, which contains electronic health records from about 150 million patients at more than 100 US healthcare organizations.

The researchers created two propensity score-matched cohorts of GLP-1 users and aspirin users, with 140,828 patients (average age, 58 years) in each. None had a history of colorectal cancer, and none were using anti-inflammatory medications other than aspirin or glucose-lowering drugs other than a GLP-1.

During a median follow-up of 5-6 years, GLP-1 use was significantly associated with reduced colorectal cancer incidence compared with aspirin use (hazard ratio [HR], 0.64). The findings were similar among people considered to be at an increased colorectal cancer risk due to health or family history: In that group, GLP-1 users had a roughly 42% lower risk of the disease (HR, 0.58).

Overall, the risk reduction with GLP-1 use was seen regardless of obesity or diabetes status, but the association was strongest among people who began treatment before age 45.

When the researchers examined individual GLP-1 medications, only semaglutide (Ozempic), liraglutide (Saxenda/Victoza), and dulaglutide (Trulicity) were associated with significant risk reductions.

As for safety outcomes, aspirin users had slightly higher rates of gastrointestinal bleeding and gastric ulcers and were more likely to suffer acute kidney injury (2.8% vs 1.15% among GLP-1 users; HR, 0.37). GLP-1 users experienced more diarrhea (6.8% vs 5.4%) and abdominal pain (19% vs 16.3%) than aspirin users did.

Jones said that both the risk reduction and safety profile associated with GLP-1s “underscore a potential public health impact” and warrant prospective validation.

Study discussant Joel Saltzman, MD, an ASCO gastrointestinal cancer expert, called the findings “thought-provoking.”

Broadly, he said, the study raises important questions about how metabolic disease, obesity, and cancer risk are interconnected — and how prevention strategies might evolve as more data emerge.

“It will certainly be interesting over the upcoming years to see how [GLP-1s] fit into colorectal cancer prevention,” said Saltzman, of Taussig Cancer Center, Cleveland Clinic, Cleveland.

Improved CRC Outcomes?

Looking beyond prevention, Jones and his colleagues conducted a separate analysis of patients diagnosed with colorectal cancer, to see whether GLP-1 therapy was associated with outcomes.

In that analysis, also using the TriNetX database, they matched 5170 patients with colorectal cancer who were on GLP-1 therapy with the same number of patients who were not on a GLP-1 medication.

Over 10 years, GLP-1 use was associated with a 53% reduction in all-cause mortality compared with nonuse (HR, 0.47), corresponding to an absolute risk reduction of 5.6% and a number needed to treat of 18.

The survival benefit was consistent across age, diabetes status, BMI, cancer stage, and treatment subgroups. GLP-1 use was not associated with a statistically significant change in the risk for metastases (HR, 0.895).

Meanwhile, another study presented at the meeting, by researchers at Mayo Clinic, Jacksonville, Florida, yielded similar findings.

Researchers led by Yajur Arya, MD, focused specifically on patients with colon cancer and comorbid obesity comparing outcomes in nearly 2000 patients taking a GLP-1 with more than 16,000 matched patients who were not on a GLP-1 agent.

Over 5 years of follow-up, GLP-1 users had a lower risk for overall mortality (HR, 0.46). They also showed decreased risks for myocardial infarction (HR, 0.83), sepsis (risk difference, -3.48%), and need for mechanical ventilation (HR, 0.49).

Both Jones and Arya stressed, however, that the findings only serve to highlight possible benefits of GLP-1 use beyond diabetes and weight management. Prospective studies, they said, are needed to better understand why these associations exist, and to potentially guide practice in the future.

None of the studies had commercial funding. Jones, Arya, and Saltzman had no relevant disclosures.

A version of this article first appeared on Medscape.com.

The GLP-1 drugs widely prescribed for diabetes and weight loss might also help reduce the risk for colorectal cancer and possibly improve outcomes in people who have the disease, according to a series of studies presented at ASCO Gastrointestinal Cancers Symposium 2026.

In one study, researchers observed a 36% lower risk for colorectal cancer among people who used GLP-1 receptor agonists vs those who used aspirin — a drug long investigated for colorectal cancer primary prevention.

While aspirin has shown “modest efficacy” in that regard, it also carries a bleeding risk that limits its use, Colton Jones, MD, a hematology and oncology fellow with The University of Texas San Antonio, told conference attendees.

Emerging evidence suggests that GLP-1s possess anti-inflammatory and anti-neoplastic properties, while some recent observational studies have linked the medications to reduced risks for certain cancers, particularly obesity-related types.

However, Jones said, research into a possible role for GLP-1s in cancer risk reduction is still in the early stages.

Prevention Potential

To conduct a “real-world” analysis, Jones and his colleagues turned to the TriNetX database, which contains electronic health records from about 150 million patients at more than 100 US healthcare organizations.

The researchers created two propensity score-matched cohorts of GLP-1 users and aspirin users, with 140,828 patients (average age, 58 years) in each. None had a history of colorectal cancer, and none were using anti-inflammatory medications other than aspirin or glucose-lowering drugs other than a GLP-1.

During a median follow-up of 5-6 years, GLP-1 use was significantly associated with reduced colorectal cancer incidence compared with aspirin use (hazard ratio [HR], 0.64). The findings were similar among people considered to be at an increased colorectal cancer risk due to health or family history: In that group, GLP-1 users had a roughly 42% lower risk of the disease (HR, 0.58).

Overall, the risk reduction with GLP-1 use was seen regardless of obesity or diabetes status, but the association was strongest among people who began treatment before age 45.

When the researchers examined individual GLP-1 medications, only semaglutide (Ozempic), liraglutide (Saxenda/Victoza), and dulaglutide (Trulicity) were associated with significant risk reductions.

As for safety outcomes, aspirin users had slightly higher rates of gastrointestinal bleeding and gastric ulcers and were more likely to suffer acute kidney injury (2.8% vs 1.15% among GLP-1 users; HR, 0.37). GLP-1 users experienced more diarrhea (6.8% vs 5.4%) and abdominal pain (19% vs 16.3%) than aspirin users did.

Jones said that both the risk reduction and safety profile associated with GLP-1s “underscore a potential public health impact” and warrant prospective validation.

Study discussant Joel Saltzman, MD, an ASCO gastrointestinal cancer expert, called the findings “thought-provoking.”

Broadly, he said, the study raises important questions about how metabolic disease, obesity, and cancer risk are interconnected — and how prevention strategies might evolve as more data emerge.

“It will certainly be interesting over the upcoming years to see how [GLP-1s] fit into colorectal cancer prevention,” said Saltzman, of Taussig Cancer Center, Cleveland Clinic, Cleveland.

Improved CRC Outcomes?

Looking beyond prevention, Jones and his colleagues conducted a separate analysis of patients diagnosed with colorectal cancer, to see whether GLP-1 therapy was associated with outcomes.

In that analysis, also using the TriNetX database, they matched 5170 patients with colorectal cancer who were on GLP-1 therapy with the same number of patients who were not on a GLP-1 medication.

Over 10 years, GLP-1 use was associated with a 53% reduction in all-cause mortality compared with nonuse (HR, 0.47), corresponding to an absolute risk reduction of 5.6% and a number needed to treat of 18.

The survival benefit was consistent across age, diabetes status, BMI, cancer stage, and treatment subgroups. GLP-1 use was not associated with a statistically significant change in the risk for metastases (HR, 0.895).

Meanwhile, another study presented at the meeting, by researchers at Mayo Clinic, Jacksonville, Florida, yielded similar findings.

Researchers led by Yajur Arya, MD, focused specifically on patients with colon cancer and comorbid obesity comparing outcomes in nearly 2000 patients taking a GLP-1 with more than 16,000 matched patients who were not on a GLP-1 agent.

Over 5 years of follow-up, GLP-1 users had a lower risk for overall mortality (HR, 0.46). They also showed decreased risks for myocardial infarction (HR, 0.83), sepsis (risk difference, -3.48%), and need for mechanical ventilation (HR, 0.49).

Both Jones and Arya stressed, however, that the findings only serve to highlight possible benefits of GLP-1 use beyond diabetes and weight management. Prospective studies, they said, are needed to better understand why these associations exist, and to potentially guide practice in the future.

None of the studies had commercial funding. Jones, Arya, and Saltzman had no relevant disclosures.

A version of this article first appeared on Medscape.com.

The GLP-1 drugs widely prescribed for diabetes and weight loss might also help reduce the risk for colorectal cancer and possibly improve outcomes in people who have the disease, according to a series of studies presented at ASCO Gastrointestinal Cancers Symposium 2026.

In one study, researchers observed a 36% lower risk for colorectal cancer among people who used GLP-1 receptor agonists vs those who used aspirin — a drug long investigated for colorectal cancer primary prevention.

While aspirin has shown “modest efficacy” in that regard, it also carries a bleeding risk that limits its use, Colton Jones, MD, a hematology and oncology fellow with The University of Texas San Antonio, told conference attendees.

Emerging evidence suggests that GLP-1s possess anti-inflammatory and anti-neoplastic properties, while some recent observational studies have linked the medications to reduced risks for certain cancers, particularly obesity-related types.

However, Jones said, research into a possible role for GLP-1s in cancer risk reduction is still in the early stages.

Prevention Potential

To conduct a “real-world” analysis, Jones and his colleagues turned to the TriNetX database, which contains electronic health records from about 150 million patients at more than 100 US healthcare organizations.

The researchers created two propensity score-matched cohorts of GLP-1 users and aspirin users, with 140,828 patients (average age, 58 years) in each. None had a history of colorectal cancer, and none were using anti-inflammatory medications other than aspirin or glucose-lowering drugs other than a GLP-1.

During a median follow-up of 5-6 years, GLP-1 use was significantly associated with reduced colorectal cancer incidence compared with aspirin use (hazard ratio [HR], 0.64). The findings were similar among people considered to be at an increased colorectal cancer risk due to health or family history: In that group, GLP-1 users had a roughly 42% lower risk of the disease (HR, 0.58).

Overall, the risk reduction with GLP-1 use was seen regardless of obesity or diabetes status, but the association was strongest among people who began treatment before age 45.

When the researchers examined individual GLP-1 medications, only semaglutide (Ozempic), liraglutide (Saxenda/Victoza), and dulaglutide (Trulicity) were associated with significant risk reductions.

As for safety outcomes, aspirin users had slightly higher rates of gastrointestinal bleeding and gastric ulcers and were more likely to suffer acute kidney injury (2.8% vs 1.15% among GLP-1 users; HR, 0.37). GLP-1 users experienced more diarrhea (6.8% vs 5.4%) and abdominal pain (19% vs 16.3%) than aspirin users did.

Jones said that both the risk reduction and safety profile associated with GLP-1s “underscore a potential public health impact” and warrant prospective validation.

Study discussant Joel Saltzman, MD, an ASCO gastrointestinal cancer expert, called the findings “thought-provoking.”

Broadly, he said, the study raises important questions about how metabolic disease, obesity, and cancer risk are interconnected — and how prevention strategies might evolve as more data emerge.

“It will certainly be interesting over the upcoming years to see how [GLP-1s] fit into colorectal cancer prevention,” said Saltzman, of Taussig Cancer Center, Cleveland Clinic, Cleveland.

Improved CRC Outcomes?

Looking beyond prevention, Jones and his colleagues conducted a separate analysis of patients diagnosed with colorectal cancer, to see whether GLP-1 therapy was associated with outcomes.

In that analysis, also using the TriNetX database, they matched 5170 patients with colorectal cancer who were on GLP-1 therapy with the same number of patients who were not on a GLP-1 medication.

Over 10 years, GLP-1 use was associated with a 53% reduction in all-cause mortality compared with nonuse (HR, 0.47), corresponding to an absolute risk reduction of 5.6% and a number needed to treat of 18.

The survival benefit was consistent across age, diabetes status, BMI, cancer stage, and treatment subgroups. GLP-1 use was not associated with a statistically significant change in the risk for metastases (HR, 0.895).

Meanwhile, another study presented at the meeting, by researchers at Mayo Clinic, Jacksonville, Florida, yielded similar findings.

Researchers led by Yajur Arya, MD, focused specifically on patients with colon cancer and comorbid obesity comparing outcomes in nearly 2000 patients taking a GLP-1 with more than 16,000 matched patients who were not on a GLP-1 agent.

Over 5 years of follow-up, GLP-1 users had a lower risk for overall mortality (HR, 0.46). They also showed decreased risks for myocardial infarction (HR, 0.83), sepsis (risk difference, -3.48%), and need for mechanical ventilation (HR, 0.49).

Both Jones and Arya stressed, however, that the findings only serve to highlight possible benefits of GLP-1 use beyond diabetes and weight management. Prospective studies, they said, are needed to better understand why these associations exist, and to potentially guide practice in the future.

None of the studies had commercial funding. Jones, Arya, and Saltzman had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Regular physical activity—especially walking—may improve fatigue and boost quality of life for people with nonmetastatic colorectal cancer during the first 2 years after diagnosis, according to research presented at ASCO Gastrointestinal Cancers Symposium 2026.

The study, which tracked over 1700 patients with colorectal cancer, found that those with nonmetastatic disease who walked for exercise 6-12 months after their diagnosis showed significant improvement in their fatigue scores over time. Their quality-of-life ratings rose in tandem.

The findings suggest that simple, sustained movement may play a meaningful role in long-term survivorship care, lead investigator Louisa Liu, MD, of Cedars-Sinai Medical Center in Los Angeles, said during a press briefing.

“Fatigue is one of the most common and debilitating symptoms our patients experience, often long after treatment ends,” Liu noted.

The new data, she said, show that an accessible form of exercise, especially when maintained over time, “can make a real difference in how patients feel and function during recovery.”

Joel Saltzman, MD, an ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic, Cleveland, agreed.

This is a “super-important study for all of us in the cancer community,” Saltzman told the briefing, especially in light of the CHALLENGE trial.

That study demonstrated that a structured exercise program can actually improve overall survival for patients with early-stage colon cancer who completed surgery and adjuvant chemotherapy.

“When you couple that with how patients feel, it really begs the question: Are we as a society doing enough cancer rehabilitation?” Saltzman said. “Everyone’s familiar with cardiac rehab, but oncologic rehabilitation is really something that really should be thought about in the future.”

Among long-term colorectal cancer survivors, nearly 40% continue to experience moderate-to-severe fatigue years after treatment — a challenge that affects functional recovery, daily activity, and quality of life.

“Yet,” Liu said, “our toolbox of effective interventions remains limited.”

Growing evidence supports physical activity as a nonpharmacologic approach for managing cancer-related fatigue. The mechanisms, Liu noted, may be multiple and include reductions in systemic inflammation, preserved muscle mass, better sleep quality and improvements in psychological stress.

In fact, current clinical guidelines recommend physical activity as part of survivorship care, but some key questions remain unanswered, Liu said.

“We still don’t fully understand when during recovery activity is most beneficial, what types of activity are best for different patients, or how these effects play out in real-world longitudinal settings, especially in colorectal cancer survivors,” she explained.

To address some of those gaps, Liu and colleagues analyzed data from 1718 patients with colorectal cancer (mean age, 67 years; 48% women) enrolled in the International ColoCare prospective cohort study. Nearly 1 in 5 had metastatic disease at diagnosis.

Physical activity was assessed at baseline and at 6, 12, and 24 months after diagnosis using a validated questionnaire. Participants’ total number of metabolic equivalent of task (MET) minutes per week — a measurement of energy spent during physical activity — were calculated for walking, moderate activities, and vigorous activities.

Total physical activity was categorized as low (fewer than 600 MET min/wk), moderate (600-3000 MET min/wk), or high (over 3000 MET min/wk).

Cancer-related fatigue and quality of life were measured using the European Organization for Research and Treatment of Cancer QLQ-C30 scale.

Overall, patients who were more physically active reported less fatigue and better quality of life as they moved further into recovery. And walking, Liu said, showed the “clearest and most consistent” association with these improved outcomes.

Among patients with nonmetastatic disease, those who reported regular walking 6-12 months after diagnosis showed significantly lower fatigue and higher quality-of-life scores over 2 years. Fatigue scores in this group improved steadily with time, from 32.5 at diagnosis to 29 at 12 months post-diagnosis and 26.8 at 24 months post-diagnosis.

Patients with metastatic disease also showed reductions in fatigue scores — from 40.7 at diagnosis to 37.1 at 12 months and 36.4 at 24 months — although those differences did not reach statistical significance.

Liu pointed out that patients with metastatic disease, not surprisingly, reported greater fatigue and poorer quality of life across all time points vs those with early-stage disease.

So, she said, “we don’t yet have strong evidence that physical activity changes the fatigue trajectory in the long run for metastatic patients. But this is an area where more targeted research is really needed.”

Looking at patterns of physical activity, the researchers found that activity levels at the time of diagnosis did not reliably predict long-term fatigue and quality-of-life outcomes. Instead, a patient’s activity level maintained between diagnosis and 1 year follow-up was a predictor of better outcomes.

“Short-term increases in physical activity didn’t seem to make a meaningful difference,” Liu said. “This suggests that when it comes to managing cancer-related fatigue, the key is to build steady, lasting habits that patients can stick with throughout their recovery.”

The study had no commercial funding. Liu and Saltzman had no disclosures.

A version of this article first appeared on Medscape.com.

Regular physical activity—especially walking—may improve fatigue and boost quality of life for people with nonmetastatic colorectal cancer during the first 2 years after diagnosis, according to research presented at ASCO Gastrointestinal Cancers Symposium 2026.

The study, which tracked over 1700 patients with colorectal cancer, found that those with nonmetastatic disease who walked for exercise 6-12 months after their diagnosis showed significant improvement in their fatigue scores over time. Their quality-of-life ratings rose in tandem.

The findings suggest that simple, sustained movement may play a meaningful role in long-term survivorship care, lead investigator Louisa Liu, MD, of Cedars-Sinai Medical Center in Los Angeles, said during a press briefing.

“Fatigue is one of the most common and debilitating symptoms our patients experience, often long after treatment ends,” Liu noted.

The new data, she said, show that an accessible form of exercise, especially when maintained over time, “can make a real difference in how patients feel and function during recovery.”

Joel Saltzman, MD, an ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic, Cleveland, agreed.

This is a “super-important study for all of us in the cancer community,” Saltzman told the briefing, especially in light of the CHALLENGE trial.

That study demonstrated that a structured exercise program can actually improve overall survival for patients with early-stage colon cancer who completed surgery and adjuvant chemotherapy.

“When you couple that with how patients feel, it really begs the question: Are we as a society doing enough cancer rehabilitation?” Saltzman said. “Everyone’s familiar with cardiac rehab, but oncologic rehabilitation is really something that really should be thought about in the future.”

Among long-term colorectal cancer survivors, nearly 40% continue to experience moderate-to-severe fatigue years after treatment — a challenge that affects functional recovery, daily activity, and quality of life.

“Yet,” Liu said, “our toolbox of effective interventions remains limited.”

Growing evidence supports physical activity as a nonpharmacologic approach for managing cancer-related fatigue. The mechanisms, Liu noted, may be multiple and include reductions in systemic inflammation, preserved muscle mass, better sleep quality and improvements in psychological stress.

In fact, current clinical guidelines recommend physical activity as part of survivorship care, but some key questions remain unanswered, Liu said.

“We still don’t fully understand when during recovery activity is most beneficial, what types of activity are best for different patients, or how these effects play out in real-world longitudinal settings, especially in colorectal cancer survivors,” she explained.

To address some of those gaps, Liu and colleagues analyzed data from 1718 patients with colorectal cancer (mean age, 67 years; 48% women) enrolled in the International ColoCare prospective cohort study. Nearly 1 in 5 had metastatic disease at diagnosis.

Physical activity was assessed at baseline and at 6, 12, and 24 months after diagnosis using a validated questionnaire. Participants’ total number of metabolic equivalent of task (MET) minutes per week — a measurement of energy spent during physical activity — were calculated for walking, moderate activities, and vigorous activities.

Total physical activity was categorized as low (fewer than 600 MET min/wk), moderate (600-3000 MET min/wk), or high (over 3000 MET min/wk).

Cancer-related fatigue and quality of life were measured using the European Organization for Research and Treatment of Cancer QLQ-C30 scale.

Overall, patients who were more physically active reported less fatigue and better quality of life as they moved further into recovery. And walking, Liu said, showed the “clearest and most consistent” association with these improved outcomes.

Among patients with nonmetastatic disease, those who reported regular walking 6-12 months after diagnosis showed significantly lower fatigue and higher quality-of-life scores over 2 years. Fatigue scores in this group improved steadily with time, from 32.5 at diagnosis to 29 at 12 months post-diagnosis and 26.8 at 24 months post-diagnosis.

Patients with metastatic disease also showed reductions in fatigue scores — from 40.7 at diagnosis to 37.1 at 12 months and 36.4 at 24 months — although those differences did not reach statistical significance.

Liu pointed out that patients with metastatic disease, not surprisingly, reported greater fatigue and poorer quality of life across all time points vs those with early-stage disease.

So, she said, “we don’t yet have strong evidence that physical activity changes the fatigue trajectory in the long run for metastatic patients. But this is an area where more targeted research is really needed.”

Looking at patterns of physical activity, the researchers found that activity levels at the time of diagnosis did not reliably predict long-term fatigue and quality-of-life outcomes. Instead, a patient’s activity level maintained between diagnosis and 1 year follow-up was a predictor of better outcomes.

“Short-term increases in physical activity didn’t seem to make a meaningful difference,” Liu said. “This suggests that when it comes to managing cancer-related fatigue, the key is to build steady, lasting habits that patients can stick with throughout their recovery.”

The study had no commercial funding. Liu and Saltzman had no disclosures.

A version of this article first appeared on Medscape.com.

Regular physical activity—especially walking—may improve fatigue and boost quality of life for people with nonmetastatic colorectal cancer during the first 2 years after diagnosis, according to research presented at ASCO Gastrointestinal Cancers Symposium 2026.

The study, which tracked over 1700 patients with colorectal cancer, found that those with nonmetastatic disease who walked for exercise 6-12 months after their diagnosis showed significant improvement in their fatigue scores over time. Their quality-of-life ratings rose in tandem.

The findings suggest that simple, sustained movement may play a meaningful role in long-term survivorship care, lead investigator Louisa Liu, MD, of Cedars-Sinai Medical Center in Los Angeles, said during a press briefing.

“Fatigue is one of the most common and debilitating symptoms our patients experience, often long after treatment ends,” Liu noted.

The new data, she said, show that an accessible form of exercise, especially when maintained over time, “can make a real difference in how patients feel and function during recovery.”

Joel Saltzman, MD, an ASCO expert in gastrointestinal cancers based at Taussig Cancer Center, Cleveland Clinic, Cleveland, agreed.

This is a “super-important study for all of us in the cancer community,” Saltzman told the briefing, especially in light of the CHALLENGE trial.

That study demonstrated that a structured exercise program can actually improve overall survival for patients with early-stage colon cancer who completed surgery and adjuvant chemotherapy.

“When you couple that with how patients feel, it really begs the question: Are we as a society doing enough cancer rehabilitation?” Saltzman said. “Everyone’s familiar with cardiac rehab, but oncologic rehabilitation is really something that really should be thought about in the future.”

Among long-term colorectal cancer survivors, nearly 40% continue to experience moderate-to-severe fatigue years after treatment — a challenge that affects functional recovery, daily activity, and quality of life.

“Yet,” Liu said, “our toolbox of effective interventions remains limited.”

Growing evidence supports physical activity as a nonpharmacologic approach for managing cancer-related fatigue. The mechanisms, Liu noted, may be multiple and include reductions in systemic inflammation, preserved muscle mass, better sleep quality and improvements in psychological stress.

In fact, current clinical guidelines recommend physical activity as part of survivorship care, but some key questions remain unanswered, Liu said.

“We still don’t fully understand when during recovery activity is most beneficial, what types of activity are best for different patients, or how these effects play out in real-world longitudinal settings, especially in colorectal cancer survivors,” she explained.

To address some of those gaps, Liu and colleagues analyzed data from 1718 patients with colorectal cancer (mean age, 67 years; 48% women) enrolled in the International ColoCare prospective cohort study. Nearly 1 in 5 had metastatic disease at diagnosis.

Physical activity was assessed at baseline and at 6, 12, and 24 months after diagnosis using a validated questionnaire. Participants’ total number of metabolic equivalent of task (MET) minutes per week — a measurement of energy spent during physical activity — were calculated for walking, moderate activities, and vigorous activities.

Total physical activity was categorized as low (fewer than 600 MET min/wk), moderate (600-3000 MET min/wk), or high (over 3000 MET min/wk).

Cancer-related fatigue and quality of life were measured using the European Organization for Research and Treatment of Cancer QLQ-C30 scale.

Overall, patients who were more physically active reported less fatigue and better quality of life as they moved further into recovery. And walking, Liu said, showed the “clearest and most consistent” association with these improved outcomes.

Among patients with nonmetastatic disease, those who reported regular walking 6-12 months after diagnosis showed significantly lower fatigue and higher quality-of-life scores over 2 years. Fatigue scores in this group improved steadily with time, from 32.5 at diagnosis to 29 at 12 months post-diagnosis and 26.8 at 24 months post-diagnosis.

Patients with metastatic disease also showed reductions in fatigue scores — from 40.7 at diagnosis to 37.1 at 12 months and 36.4 at 24 months — although those differences did not reach statistical significance.

Liu pointed out that patients with metastatic disease, not surprisingly, reported greater fatigue and poorer quality of life across all time points vs those with early-stage disease.

So, she said, “we don’t yet have strong evidence that physical activity changes the fatigue trajectory in the long run for metastatic patients. But this is an area where more targeted research is really needed.”

Looking at patterns of physical activity, the researchers found that activity levels at the time of diagnosis did not reliably predict long-term fatigue and quality-of-life outcomes. Instead, a patient’s activity level maintained between diagnosis and 1 year follow-up was a predictor of better outcomes.

“Short-term increases in physical activity didn’t seem to make a meaningful difference,” Liu said. “This suggests that when it comes to managing cancer-related fatigue, the key is to build steady, lasting habits that patients can stick with throughout their recovery.”

The study had no commercial funding. Liu and Saltzman had no disclosures.

A version of this article first appeared on Medscape.com.

Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.

In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.

The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.

The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.

The study was published online in Cancer Investigation.
 

Effects Beyond Glucose-Lowering

Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.

Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.

To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.

Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).

When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).

Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
 

Intriguing and Promising — but Further Studies Needed

“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.

“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.

For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.

Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”

Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.

The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.

In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.

This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.

In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.

The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.

The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.

The study was published online in Cancer Investigation.
 

Effects Beyond Glucose-Lowering

Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.

Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.

To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.

Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).

When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).

Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
 

Intriguing and Promising — but Further Studies Needed

“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.

“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.

For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.

Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”

Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.

The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.

In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.

This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.

In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.

The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.

The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.

The study was published online in Cancer Investigation.
 

Effects Beyond Glucose-Lowering

Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.

Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.

To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.

Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).

When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).

Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
 

Intriguing and Promising — but Further Studies Needed

“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.

“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.

For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.

Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”

Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.

The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.

In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.

This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.

A version of this article first appeared on Medscape.com.