Colon and Rectal

DNA methylation-derived biomarkers called Protein EpiScores may improve the accuracy of disease-free and overall survival prediction in patients with colorectal cancer (CRC), compared with traditional clinical risk factors alone, suggest results of a prospective study.

Although Protein EpiScores require further validation before they are ready for clinical use, the present data offer insights into the underlying processes shaping CRC outcomes, lead author Alicia R. Richards, PhD, of Moffitt Cancer Center, Tampa, Florida, and colleagues wrote in Clinical Epigenetics.

“The immediate value of our findings is highlighting biological pathways like immune suppression and coagulation as drivers of poor outcomes,” senior author Jacob K. Kresovich, PhD, of Moffitt Cancer Center, told Medscape Medical News.

What Are Protein EpiScores?

Previous studies have evaluated epigenetic clocks, which are derived from DNA methylation profiles, as markers for CRC risk. However, these clocks cannot pinpoint specific biological drivers of cancer progression, the investigators wrote.

Protein EpiScores may fill this gap; they were developed based on previous work suggesting that DNA methylation profiles may improve disease prediction based on circulating proteins (eg, C-reactive protein) and physiologic traits (eg, smoking status) beyond directly measuring those same variables.

“Protein EpiScores may therefore represent a complementary class of biomarker to direct measurements,” the investigators wrote.

Although Protein EpiScores have helped uncover biological processes driving various conditions such as cardiovascular disease and cancer, this is the first study to evaluate them specifically in the context of cancer survival.

How Did This Study Evaluate Protein EpiScores in Patients With CRC?

The present study involved 136 patients with newly diagnosed CRC from the prospective ColoCare Study.

For each patient, the investigators recorded 107 Protein EpiScores from pretreatment whole blood samples. Disease-free and overall survival were monitored over a median follow-up of 7.3 years and as long as 13.8 years. During follow-up, 26% of patients experienced disease recurrence, and 35% died.

With these data, the investigators compared the predictive power of the Protein EpiScores vs traditional clinical risk factors for disease-free and overall survival. “We used the standard factors doctors routinely collect before treatment starts to assess prognosis, including tumor stage, age at cancer diagnosis, sex, body mass index, race, and tumor location,” Kresovich said. “These are well-established predictors readily available from medical records.”

What Were the Key Findings?

Adding specific Protein EpiScores to the standard clinical risk factors significantly improved prognostic accuracy for survival.

After adjusting for confounding variables, the HCII, VEGFA, CCL17, and LGALS3BP Protein EpiScores were each independently associated with worse disease-free survival, with hazard ratios ranging from 1.62 to 1.71. Adding these scores to the clinical model improved the concordance index (C-index) from 0.64 to 0.70.

The LGALS3BP Protein EpiScore was also independently linked to overall survival, with a hazard ratio of 1.80. Adding this score to the model raised the C-index from 0.70 to 0.75.

Finally, the HCII, LGALS3BP, MMP12, and VEGFA Protein EpiScores were tied to both disease-free and overall survival with hazard ratios above 1.50.

Are These Findings Practice-Changing?

“The improvements [in prognostic accuracy] are modest but potentially meaningful and comparable to gains from other established biomarkers,” Kresovich said. “The 6-point improvement for recurrence (C-index 0.64 to 0.70) resulted in 34% of patients being reclassified into more accurate risk categories.”

In theory, this could have a meaningful clinical impact.

“In cancer care, even incremental gains matter if they prevent undertreating high-risk patients or overtreating low-risk ones,” Kresovich said.

Despite this potential, he was clear that more work is needed.

“If our findings are validated in other epidemiologic settings, these Protein EpiScores could eventually complement existing risk tools, but we’re realistically several years from clinical implementation,” Kresovich said. “We see these current findings more as a research tool that requires validation in larger cohorts before clinical use.”

How Might These Findings Shape Future Research?

Although more studies are needed before clinical rollout, the present findings point to key biological pathways, such as those involving immune suppression and coagulation, which may be driving worse outcomes in patients with CRC.

“This information can guide basic scientists and mechanistic studies to identify potential therapeutic targets,” Kresovich said.

Beyond evaluating Protein EpiScores in larger patient populations, future studies may also need to recruit a more diverse patient population, given the present cohort was 93% White.

Although the investigators noted that “the racial homogeneity reduced potential confounding by ancestry,” they also explained that “Protein EpiScores were developed in European populations, and their translation to individuals with different ancestries has not been closely examined.”

The study was supported by the Miles for Moffitt Team Science Mechanism. The investigators reported no relevant conflicts of interest.

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

DNA methylation-derived biomarkers called Protein EpiScores may improve the accuracy of disease-free and overall survival prediction in patients with colorectal cancer (CRC), compared with traditional clinical risk factors alone, suggest results of a prospective study.

Although Protein EpiScores require further validation before they are ready for clinical use, the present data offer insights into the underlying processes shaping CRC outcomes, lead author Alicia R. Richards, PhD, of Moffitt Cancer Center, Tampa, Florida, and colleagues wrote in Clinical Epigenetics.

“The immediate value of our findings is highlighting biological pathways like immune suppression and coagulation as drivers of poor outcomes,” senior author Jacob K. Kresovich, PhD, of Moffitt Cancer Center, told Medscape Medical News.

What Are Protein EpiScores?

Previous studies have evaluated epigenetic clocks, which are derived from DNA methylation profiles, as markers for CRC risk. However, these clocks cannot pinpoint specific biological drivers of cancer progression, the investigators wrote.

Protein EpiScores may fill this gap; they were developed based on previous work suggesting that DNA methylation profiles may improve disease prediction based on circulating proteins (eg, C-reactive protein) and physiologic traits (eg, smoking status) beyond directly measuring those same variables.

“Protein EpiScores may therefore represent a complementary class of biomarker to direct measurements,” the investigators wrote.

Although Protein EpiScores have helped uncover biological processes driving various conditions such as cardiovascular disease and cancer, this is the first study to evaluate them specifically in the context of cancer survival.

How Did This Study Evaluate Protein EpiScores in Patients With CRC?

The present study involved 136 patients with newly diagnosed CRC from the prospective ColoCare Study.

For each patient, the investigators recorded 107 Protein EpiScores from pretreatment whole blood samples. Disease-free and overall survival were monitored over a median follow-up of 7.3 years and as long as 13.8 years. During follow-up, 26% of patients experienced disease recurrence, and 35% died.

With these data, the investigators compared the predictive power of the Protein EpiScores vs traditional clinical risk factors for disease-free and overall survival. “We used the standard factors doctors routinely collect before treatment starts to assess prognosis, including tumor stage, age at cancer diagnosis, sex, body mass index, race, and tumor location,” Kresovich said. “These are well-established predictors readily available from medical records.”

What Were the Key Findings?

Adding specific Protein EpiScores to the standard clinical risk factors significantly improved prognostic accuracy for survival.

After adjusting for confounding variables, the HCII, VEGFA, CCL17, and LGALS3BP Protein EpiScores were each independently associated with worse disease-free survival, with hazard ratios ranging from 1.62 to 1.71. Adding these scores to the clinical model improved the concordance index (C-index) from 0.64 to 0.70.

The LGALS3BP Protein EpiScore was also independently linked to overall survival, with a hazard ratio of 1.80. Adding this score to the model raised the C-index from 0.70 to 0.75.

Finally, the HCII, LGALS3BP, MMP12, and VEGFA Protein EpiScores were tied to both disease-free and overall survival with hazard ratios above 1.50.

Are These Findings Practice-Changing?

“The improvements [in prognostic accuracy] are modest but potentially meaningful and comparable to gains from other established biomarkers,” Kresovich said. “The 6-point improvement for recurrence (C-index 0.64 to 0.70) resulted in 34% of patients being reclassified into more accurate risk categories.”

In theory, this could have a meaningful clinical impact.

“In cancer care, even incremental gains matter if they prevent undertreating high-risk patients or overtreating low-risk ones,” Kresovich said.

Despite this potential, he was clear that more work is needed.

“If our findings are validated in other epidemiologic settings, these Protein EpiScores could eventually complement existing risk tools, but we’re realistically several years from clinical implementation,” Kresovich said. “We see these current findings more as a research tool that requires validation in larger cohorts before clinical use.”

How Might These Findings Shape Future Research?

Although more studies are needed before clinical rollout, the present findings point to key biological pathways, such as those involving immune suppression and coagulation, which may be driving worse outcomes in patients with CRC.

“This information can guide basic scientists and mechanistic studies to identify potential therapeutic targets,” Kresovich said.

Beyond evaluating Protein EpiScores in larger patient populations, future studies may also need to recruit a more diverse patient population, given the present cohort was 93% White.

Although the investigators noted that “the racial homogeneity reduced potential confounding by ancestry,” they also explained that “Protein EpiScores were developed in European populations, and their translation to individuals with different ancestries has not been closely examined.”

The study was supported by the Miles for Moffitt Team Science Mechanism. The investigators reported no relevant conflicts of interest.

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

DNA methylation-derived biomarkers called Protein EpiScores may improve the accuracy of disease-free and overall survival prediction in patients with colorectal cancer (CRC), compared with traditional clinical risk factors alone, suggest results of a prospective study.

Although Protein EpiScores require further validation before they are ready for clinical use, the present data offer insights into the underlying processes shaping CRC outcomes, lead author Alicia R. Richards, PhD, of Moffitt Cancer Center, Tampa, Florida, and colleagues wrote in Clinical Epigenetics.

“The immediate value of our findings is highlighting biological pathways like immune suppression and coagulation as drivers of poor outcomes,” senior author Jacob K. Kresovich, PhD, of Moffitt Cancer Center, told Medscape Medical News.

What Are Protein EpiScores?

Previous studies have evaluated epigenetic clocks, which are derived from DNA methylation profiles, as markers for CRC risk. However, these clocks cannot pinpoint specific biological drivers of cancer progression, the investigators wrote.

Protein EpiScores may fill this gap; they were developed based on previous work suggesting that DNA methylation profiles may improve disease prediction based on circulating proteins (eg, C-reactive protein) and physiologic traits (eg, smoking status) beyond directly measuring those same variables.

“Protein EpiScores may therefore represent a complementary class of biomarker to direct measurements,” the investigators wrote.

Although Protein EpiScores have helped uncover biological processes driving various conditions such as cardiovascular disease and cancer, this is the first study to evaluate them specifically in the context of cancer survival.

How Did This Study Evaluate Protein EpiScores in Patients With CRC?

The present study involved 136 patients with newly diagnosed CRC from the prospective ColoCare Study.

For each patient, the investigators recorded 107 Protein EpiScores from pretreatment whole blood samples. Disease-free and overall survival were monitored over a median follow-up of 7.3 years and as long as 13.8 years. During follow-up, 26% of patients experienced disease recurrence, and 35% died.

With these data, the investigators compared the predictive power of the Protein EpiScores vs traditional clinical risk factors for disease-free and overall survival. “We used the standard factors doctors routinely collect before treatment starts to assess prognosis, including tumor stage, age at cancer diagnosis, sex, body mass index, race, and tumor location,” Kresovich said. “These are well-established predictors readily available from medical records.”

What Were the Key Findings?

Adding specific Protein EpiScores to the standard clinical risk factors significantly improved prognostic accuracy for survival.

After adjusting for confounding variables, the HCII, VEGFA, CCL17, and LGALS3BP Protein EpiScores were each independently associated with worse disease-free survival, with hazard ratios ranging from 1.62 to 1.71. Adding these scores to the clinical model improved the concordance index (C-index) from 0.64 to 0.70.

The LGALS3BP Protein EpiScore was also independently linked to overall survival, with a hazard ratio of 1.80. Adding this score to the model raised the C-index from 0.70 to 0.75.

Finally, the HCII, LGALS3BP, MMP12, and VEGFA Protein EpiScores were tied to both disease-free and overall survival with hazard ratios above 1.50.

Are These Findings Practice-Changing?

“The improvements [in prognostic accuracy] are modest but potentially meaningful and comparable to gains from other established biomarkers,” Kresovich said. “The 6-point improvement for recurrence (C-index 0.64 to 0.70) resulted in 34% of patients being reclassified into more accurate risk categories.”

In theory, this could have a meaningful clinical impact.

“In cancer care, even incremental gains matter if they prevent undertreating high-risk patients or overtreating low-risk ones,” Kresovich said.

Despite this potential, he was clear that more work is needed.

“If our findings are validated in other epidemiologic settings, these Protein EpiScores could eventually complement existing risk tools, but we’re realistically several years from clinical implementation,” Kresovich said. “We see these current findings more as a research tool that requires validation in larger cohorts before clinical use.”

How Might These Findings Shape Future Research?

Although more studies are needed before clinical rollout, the present findings point to key biological pathways, such as those involving immune suppression and coagulation, which may be driving worse outcomes in patients with CRC.

“This information can guide basic scientists and mechanistic studies to identify potential therapeutic targets,” Kresovich said.

Beyond evaluating Protein EpiScores in larger patient populations, future studies may also need to recruit a more diverse patient population, given the present cohort was 93% White.

Although the investigators noted that “the racial homogeneity reduced potential confounding by ancestry,” they also explained that “Protein EpiScores were developed in European populations, and their translation to individuals with different ancestries has not been closely examined.”

The study was supported by the Miles for Moffitt Team Science Mechanism. The investigators reported no relevant conflicts of interest.

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

TOPLINE:

Mailed fecal immunochemical test (FIT) kits with reminder phone calls promote colorectal cancer (CRC) screening among veterans without recent primary care visits. Among 782 veterans in a randomized controlled trial (RCT), mailed FITs resulted in a 26.1% screening completion rate within 6 months, compared with 5.8% for usual care and 7.7% for mailed invitations with reminders. Improving screening in this population may help CRC morbidity and mortality among veterans.

METHODOLOGY:

• Researchers conducted a 3-arm pragmatic RCT at the US Department of Verterans Affairs (VA) Corporal Michael J. Crescenz VA Medical Center (CMC-VAMC), enrolling veterans aged 50 to 75 years without a primary care visit within 18 months.
• Participants were randomized 1:1:1 to usual care (n = 260), mailed clinic-based screening invitations with reminder calls (n = 261), or mailed home FIT outreach plus prenotification letter and reminder phone calls (n = 261).
• Outcome measures included documented completion of CRC screening within 6 months after randomization in the electronic health record (EHR); a secondary outcome was FIT return within 6 months among those mailed FIT.
• Eligibility and exclusions were based on chart review and EHR criteria (eg, excluding symptoms, family history, inflammatory bowel disease, prior resection, or being current by having undergone a colonoscopy within 10 years, sigmoidoscopy or barium enema within 5 years, or fecal occult blood testing within 1 year).

TAKEAWAY

• CRC screening completion within 6 months is 26.1% with mailed FIT vs 5.8% with usual care (RD, 20.3%; 95% CI, 14.3%-26.3%; RR, 4.5; 95% CI, 2.7-7.7; P < .001).
• CRC screening completion within 6 months is 26.1% with mailed FIT vs 7.7% with mailed invitation plus reminders (RD, 18.4%; 95% CI, 12.2%-24.6%; RR, 3.4; 95% CI, 2.1-5.4; P < .001).
• Screening completion does not differ between mailed invitation plus reminders (7.7%) and usual care (5.8%), and the comparison is not statistically supported (RR, 1.3; P = .39).
• No statistically significant differences in screening completion are reported by age or race/ethnicity, and investigators also report no significant differences in FIT return by age or race/ethnicity in the secondary analysis.

IN PRACTICE

“This research represents the first pragmatic RCT of mailed FIT outreach screening among veterans who have not recently (18 months) used primary care services offered by the VA. In this work, there were large relative, and absolute differences in CRC screening participation rate between veterans offered home FIT screening and those who received usual care (RR = 4.52, RD = 20.2%) or a mailed invitation plus reminders (RR = 3.40, RD = 18.4%)," wrote the authors.

SOURCE

The study was led by Matthew A. Goldshore, MD, PhD, MPH, of the CMC-VAMC . It was published online in Am J Prev Med.

LIMITATIONS

The study was not able identify differences in screening completion or FIT return by patient demographic characteristics such as age and race. The sample was randomized from predominantly male veterans cared for at a single VA medical center, limiting generalizability and reducing external validity. Follow-up and subsequent evaluation of FIT-positive participants is needed for the success of a mailed FIT intervention; of the 3 FIT-positive participants who should have received follow-up evaluation, only 1 underwent colonoscopy, highlighting the challenge of FIT to colonoscopy among participants who do not use care regularly at the CMC-VAMC.

DISCLOSURES

This trial received funding from an VA Health Services Research and Development Service award, with E. Carter Paulson, MD, MSCE, and Chyke A. Doubeni, MD, MPH, serving as principal investigators. Chyke A. Doubeni received support from grant number RO1CA 213645, and Shivan J. Mehta received support from grant number K08CA 234326, both from the National Cancer Institute of the National Institutes of Health. The authors reported no financial disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Mailed fecal immunochemical test (FIT) kits with reminder phone calls promote colorectal cancer (CRC) screening among veterans without recent primary care visits. Among 782 veterans in a randomized controlled trial (RCT), mailed FITs resulted in a 26.1% screening completion rate within 6 months, compared with 5.8% for usual care and 7.7% for mailed invitations with reminders. Improving screening in this population may help CRC morbidity and mortality among veterans.

METHODOLOGY:

• Researchers conducted a 3-arm pragmatic RCT at the US Department of Verterans Affairs (VA) Corporal Michael J. Crescenz VA Medical Center (CMC-VAMC), enrolling veterans aged 50 to 75 years without a primary care visit within 18 months.
• Participants were randomized 1:1:1 to usual care (n = 260), mailed clinic-based screening invitations with reminder calls (n = 261), or mailed home FIT outreach plus prenotification letter and reminder phone calls (n = 261).
• Outcome measures included documented completion of CRC screening within 6 months after randomization in the electronic health record (EHR); a secondary outcome was FIT return within 6 months among those mailed FIT.
• Eligibility and exclusions were based on chart review and EHR criteria (eg, excluding symptoms, family history, inflammatory bowel disease, prior resection, or being current by having undergone a colonoscopy within 10 years, sigmoidoscopy or barium enema within 5 years, or fecal occult blood testing within 1 year).

TAKEAWAY

• CRC screening completion within 6 months is 26.1% with mailed FIT vs 5.8% with usual care (RD, 20.3%; 95% CI, 14.3%-26.3%; RR, 4.5; 95% CI, 2.7-7.7; P < .001).
• CRC screening completion within 6 months is 26.1% with mailed FIT vs 7.7% with mailed invitation plus reminders (RD, 18.4%; 95% CI, 12.2%-24.6%; RR, 3.4; 95% CI, 2.1-5.4; P < .001).
• Screening completion does not differ between mailed invitation plus reminders (7.7%) and usual care (5.8%), and the comparison is not statistically supported (RR, 1.3; P = .39).
• No statistically significant differences in screening completion are reported by age or race/ethnicity, and investigators also report no significant differences in FIT return by age or race/ethnicity in the secondary analysis.

IN PRACTICE

“This research represents the first pragmatic RCT of mailed FIT outreach screening among veterans who have not recently (18 months) used primary care services offered by the VA. In this work, there were large relative, and absolute differences in CRC screening participation rate between veterans offered home FIT screening and those who received usual care (RR = 4.52, RD = 20.2%) or a mailed invitation plus reminders (RR = 3.40, RD = 18.4%)," wrote the authors.

SOURCE

The study was led by Matthew A. Goldshore, MD, PhD, MPH, of the CMC-VAMC . It was published online in Am J Prev Med.

LIMITATIONS

The study was not able identify differences in screening completion or FIT return by patient demographic characteristics such as age and race. The sample was randomized from predominantly male veterans cared for at a single VA medical center, limiting generalizability and reducing external validity. Follow-up and subsequent evaluation of FIT-positive participants is needed for the success of a mailed FIT intervention; of the 3 FIT-positive participants who should have received follow-up evaluation, only 1 underwent colonoscopy, highlighting the challenge of FIT to colonoscopy among participants who do not use care regularly at the CMC-VAMC.

DISCLOSURES

This trial received funding from an VA Health Services Research and Development Service award, with E. Carter Paulson, MD, MSCE, and Chyke A. Doubeni, MD, MPH, serving as principal investigators. Chyke A. Doubeni received support from grant number RO1CA 213645, and Shivan J. Mehta received support from grant number K08CA 234326, both from the National Cancer Institute of the National Institutes of Health. The authors reported no financial disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Mailed fecal immunochemical test (FIT) kits with reminder phone calls promote colorectal cancer (CRC) screening among veterans without recent primary care visits. Among 782 veterans in a randomized controlled trial (RCT), mailed FITs resulted in a 26.1% screening completion rate within 6 months, compared with 5.8% for usual care and 7.7% for mailed invitations with reminders. Improving screening in this population may help CRC morbidity and mortality among veterans.

METHODOLOGY:

• Researchers conducted a 3-arm pragmatic RCT at the US Department of Verterans Affairs (VA) Corporal Michael J. Crescenz VA Medical Center (CMC-VAMC), enrolling veterans aged 50 to 75 years without a primary care visit within 18 months.
• Participants were randomized 1:1:1 to usual care (n = 260), mailed clinic-based screening invitations with reminder calls (n = 261), or mailed home FIT outreach plus prenotification letter and reminder phone calls (n = 261).
• Outcome measures included documented completion of CRC screening within 6 months after randomization in the electronic health record (EHR); a secondary outcome was FIT return within 6 months among those mailed FIT.
• Eligibility and exclusions were based on chart review and EHR criteria (eg, excluding symptoms, family history, inflammatory bowel disease, prior resection, or being current by having undergone a colonoscopy within 10 years, sigmoidoscopy or barium enema within 5 years, or fecal occult blood testing within 1 year).

TAKEAWAY

• CRC screening completion within 6 months is 26.1% with mailed FIT vs 5.8% with usual care (RD, 20.3%; 95% CI, 14.3%-26.3%; RR, 4.5; 95% CI, 2.7-7.7; P < .001).
• CRC screening completion within 6 months is 26.1% with mailed FIT vs 7.7% with mailed invitation plus reminders (RD, 18.4%; 95% CI, 12.2%-24.6%; RR, 3.4; 95% CI, 2.1-5.4; P < .001).
• Screening completion does not differ between mailed invitation plus reminders (7.7%) and usual care (5.8%), and the comparison is not statistically supported (RR, 1.3; P = .39).
• No statistically significant differences in screening completion are reported by age or race/ethnicity, and investigators also report no significant differences in FIT return by age or race/ethnicity in the secondary analysis.

IN PRACTICE

“This research represents the first pragmatic RCT of mailed FIT outreach screening among veterans who have not recently (18 months) used primary care services offered by the VA. In this work, there were large relative, and absolute differences in CRC screening participation rate between veterans offered home FIT screening and those who received usual care (RR = 4.52, RD = 20.2%) or a mailed invitation plus reminders (RR = 3.40, RD = 18.4%)," wrote the authors.

SOURCE

The study was led by Matthew A. Goldshore, MD, PhD, MPH, of the CMC-VAMC . It was published online in Am J Prev Med.

LIMITATIONS

The study was not able identify differences in screening completion or FIT return by patient demographic characteristics such as age and race. The sample was randomized from predominantly male veterans cared for at a single VA medical center, limiting generalizability and reducing external validity. Follow-up and subsequent evaluation of FIT-positive participants is needed for the success of a mailed FIT intervention; of the 3 FIT-positive participants who should have received follow-up evaluation, only 1 underwent colonoscopy, highlighting the challenge of FIT to colonoscopy among participants who do not use care regularly at the CMC-VAMC.

DISCLOSURES

This trial received funding from an VA Health Services Research and Development Service award, with E. Carter Paulson, MD, MSCE, and Chyke A. Doubeni, MD, MPH, serving as principal investigators. Chyke A. Doubeni received support from grant number RO1CA 213645, and Shivan J. Mehta received support from grant number K08CA 234326, both from the National Cancer Institute of the National Institutes of Health. The authors reported no financial disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: 

A recalibrated environmental risk score for colorectal cancer (CRC) shows improved predictive performance in a study of 227,504 male veterans. The veteran-tailored score could help personalize screening better than previous models.

METHODOLOGY: 

• Demographic, lifestyle, and CRC data from 2011 to 2022 were abstracted from survey responses and health records of 227,504 male Million Veteran Program (MVP) participants, with complete data needed to construct the environmental risk score (e-Score).
• Researchers randomly split the male sample into 2 halves to produce training and validation samples (each n = 113,752; CRC cases n = 590) using simple random sampling with strata based on the CRC variable.
• Weighting for each environmental factor's effect size was recalculated using US Department of Veterans Affairs training data to create a recalibrated e-Score, which was compared with the original weighted e-Score in the validation sample.
• Analysis included nested multiple logistic regression models testing associations between quintiles for recalibrated and original e-Scores, with likelihood ratio tests used to compare model performance.
• Factors used to construct the e-Score included BMI, height, diabetes diagnosis, aspirin use, nonsteroidal anti-inflammatory drug use, educational attainment, physical activity level, smoking status, alcohol use, and dietary intake of fiber, calcium, folate, processed meats, red meat, fruits, vegetables, and total energy.

TAKEAWAY:

• The recalibrated e-Score showed a significant association with CRC, with higher quintiles indicating increased risk.
• In the validation sample, the recalibrated e-Score model significantly improved the base model performance (P < .001), while the original GECCO e-Score model did not show significant improvement (P = .07).
• The recalibrated e-Score model quintile 5 was associated with significantly higher odds for CRC compared with quintile 1 (odds ratio [OR], 1.79; 95% CI, 1.38-2.33; P for trend < .001).
• Black participants had higher odds for CRC compared with the White reference group across all models (base model OR, 1.46; 95% CI, 1.13-1.92; GECCO e-Score model OR, 1.44; 95% CI, 1.09-1.88; and recalibrated e-Score model OR, 1.38; 95% CI, 1.05-1.82).

IN PRACTICE:

"Despite the robust methods used in the work by the GECCO study upon which our study was based, an e-Score using their study’s weighting was not significantly associated with colorectal cancer among the male veteran sample. However, data from nearly a quarter million (n = 227,504) male US veteran participants of the MVP were used to recalibrate the e-Score to be veteran specific, and the recalibrated e-Score validation showed that it was significantly associated with colorectal cancer," wrote the authors of the study.

SOURCE:

The study was led by April R. Williams, US Department of Veterans Affairs Million Veteran Program Coordinating Center in Boston. It was published online in Cancer Epidemiology, Biomarkers & Prevention.

LIMITATIONS:

The study's limitations include potential recall and self-selection bias due to the use of self-reported data from the MVP. The generalizability of the findings may be limited to the veteran population, and the sample of Black veterans may have been insufficient for conclusive analysis. Additionally, the study did not include female participants due to insufficient data for a veteran-specific e-Score.

DISCLOSURES:

B.A. Sullivan disclosed receiving grants from the American Gastroenterological Association. D. Lieberman reported support from Geneoscopy, UDX, and ColoWrap. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: 

A recalibrated environmental risk score for colorectal cancer (CRC) shows improved predictive performance in a study of 227,504 male veterans. The veteran-tailored score could help personalize screening better than previous models.

METHODOLOGY: 

• Demographic, lifestyle, and CRC data from 2011 to 2022 were abstracted from survey responses and health records of 227,504 male Million Veteran Program (MVP) participants, with complete data needed to construct the environmental risk score (e-Score).
• Researchers randomly split the male sample into 2 halves to produce training and validation samples (each n = 113,752; CRC cases n = 590) using simple random sampling with strata based on the CRC variable.
• Weighting for each environmental factor's effect size was recalculated using US Department of Veterans Affairs training data to create a recalibrated e-Score, which was compared with the original weighted e-Score in the validation sample.
• Analysis included nested multiple logistic regression models testing associations between quintiles for recalibrated and original e-Scores, with likelihood ratio tests used to compare model performance.
• Factors used to construct the e-Score included BMI, height, diabetes diagnosis, aspirin use, nonsteroidal anti-inflammatory drug use, educational attainment, physical activity level, smoking status, alcohol use, and dietary intake of fiber, calcium, folate, processed meats, red meat, fruits, vegetables, and total energy.

TAKEAWAY:

• The recalibrated e-Score showed a significant association with CRC, with higher quintiles indicating increased risk.
• In the validation sample, the recalibrated e-Score model significantly improved the base model performance (P < .001), while the original GECCO e-Score model did not show significant improvement (P = .07).
• The recalibrated e-Score model quintile 5 was associated with significantly higher odds for CRC compared with quintile 1 (odds ratio [OR], 1.79; 95% CI, 1.38-2.33; P for trend < .001).
• Black participants had higher odds for CRC compared with the White reference group across all models (base model OR, 1.46; 95% CI, 1.13-1.92; GECCO e-Score model OR, 1.44; 95% CI, 1.09-1.88; and recalibrated e-Score model OR, 1.38; 95% CI, 1.05-1.82).

IN PRACTICE:

"Despite the robust methods used in the work by the GECCO study upon which our study was based, an e-Score using their study’s weighting was not significantly associated with colorectal cancer among the male veteran sample. However, data from nearly a quarter million (n = 227,504) male US veteran participants of the MVP were used to recalibrate the e-Score to be veteran specific, and the recalibrated e-Score validation showed that it was significantly associated with colorectal cancer," wrote the authors of the study.

SOURCE:

The study was led by April R. Williams, US Department of Veterans Affairs Million Veteran Program Coordinating Center in Boston. It was published online in Cancer Epidemiology, Biomarkers & Prevention.

LIMITATIONS:

The study's limitations include potential recall and self-selection bias due to the use of self-reported data from the MVP. The generalizability of the findings may be limited to the veteran population, and the sample of Black veterans may have been insufficient for conclusive analysis. Additionally, the study did not include female participants due to insufficient data for a veteran-specific e-Score.

DISCLOSURES:

B.A. Sullivan disclosed receiving grants from the American Gastroenterological Association. D. Lieberman reported support from Geneoscopy, UDX, and ColoWrap. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: 

A recalibrated environmental risk score for colorectal cancer (CRC) shows improved predictive performance in a study of 227,504 male veterans. The veteran-tailored score could help personalize screening better than previous models.

METHODOLOGY: 

• Demographic, lifestyle, and CRC data from 2011 to 2022 were abstracted from survey responses and health records of 227,504 male Million Veteran Program (MVP) participants, with complete data needed to construct the environmental risk score (e-Score).
• Researchers randomly split the male sample into 2 halves to produce training and validation samples (each n = 113,752; CRC cases n = 590) using simple random sampling with strata based on the CRC variable.
• Weighting for each environmental factor's effect size was recalculated using US Department of Veterans Affairs training data to create a recalibrated e-Score, which was compared with the original weighted e-Score in the validation sample.
• Analysis included nested multiple logistic regression models testing associations between quintiles for recalibrated and original e-Scores, with likelihood ratio tests used to compare model performance.
• Factors used to construct the e-Score included BMI, height, diabetes diagnosis, aspirin use, nonsteroidal anti-inflammatory drug use, educational attainment, physical activity level, smoking status, alcohol use, and dietary intake of fiber, calcium, folate, processed meats, red meat, fruits, vegetables, and total energy.

TAKEAWAY:

• The recalibrated e-Score showed a significant association with CRC, with higher quintiles indicating increased risk.
• In the validation sample, the recalibrated e-Score model significantly improved the base model performance (P < .001), while the original GECCO e-Score model did not show significant improvement (P = .07).
• The recalibrated e-Score model quintile 5 was associated with significantly higher odds for CRC compared with quintile 1 (odds ratio [OR], 1.79; 95% CI, 1.38-2.33; P for trend < .001).
• Black participants had higher odds for CRC compared with the White reference group across all models (base model OR, 1.46; 95% CI, 1.13-1.92; GECCO e-Score model OR, 1.44; 95% CI, 1.09-1.88; and recalibrated e-Score model OR, 1.38; 95% CI, 1.05-1.82).

IN PRACTICE:

"Despite the robust methods used in the work by the GECCO study upon which our study was based, an e-Score using their study’s weighting was not significantly associated with colorectal cancer among the male veteran sample. However, data from nearly a quarter million (n = 227,504) male US veteran participants of the MVP were used to recalibrate the e-Score to be veteran specific, and the recalibrated e-Score validation showed that it was significantly associated with colorectal cancer," wrote the authors of the study.

SOURCE:

The study was led by April R. Williams, US Department of Veterans Affairs Million Veteran Program Coordinating Center in Boston. It was published online in Cancer Epidemiology, Biomarkers & Prevention.

LIMITATIONS:

The study's limitations include potential recall and self-selection bias due to the use of self-reported data from the MVP. The generalizability of the findings may be limited to the veteran population, and the sample of Black veterans may have been insufficient for conclusive analysis. Additionally, the study did not include female participants due to insufficient data for a veteran-specific e-Score.

DISCLOSURES:

B.A. Sullivan disclosed receiving grants from the American Gastroenterological Association. D. Lieberman reported support from Geneoscopy, UDX, and ColoWrap. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

First, the good news: Fewer Americans aged < 50 years are dying from cancer vs just a decade ago — reflecting progress in prevention, early detection, and treatment. There is, however, one big exception. Colorectal cancer mortality has been steadily inching up, and the disease now stands as the leading cause of cancer death in this age group, up from the fifth-leading in the early 1990s.

Those are the major findings of a recent study by the American Cancer Society (ACS), published as a research letter in JAMA.

Using SEER data, researchers found that the overall age-adjusted cancer death rate among Americans aged < 50 years dropped by 44% between 1990 and 2023 — from 25.5 to 14.2 per 100,000. And for 4 of the 5 leading causes of cancer death, there were mean annual declines from 2014 to 2023. The biggest change was in lung cancer deaths, which fell by an average of 5.7% per year. Meanwhile, leukemia and breast cancer deaths showed annual declines of 2.3% and 1.4%, respectively, despite rising incidences of both diseases among younger Americans.

The outlier is colorectal cancer, where mortality has been rising by about 1% per year since 2005. And it’s a pattern seen in both men and women.

Study coauthor Nikita Sandeep Wagle, PhD, MBBS, principal scientist, Cancer Surveillance Research at the ACS, and Arif Kamal, MD, ACS chief patient officer, discussed the research and its implications with Medscape Medical News.

Can you offer some possible reasons for the declining mortality in most of the cancers you studied?

Wagle: Mortality is going down for most of the cancers because we are getting better at finding cancers earlier and treating them more effectively. We have also seen improvements in screening, imaging, and therapy, and that means more people are being diagnosed at earlier stages and are surviving longer after diagnosis.

Regarding the rise in colorectal cancer mortality, do you think it's due to the rising incidence of early-onset colorectal cancer?

Kamal: Partially, but not completely, because the relationship between incidence and mortality is not always straightforward. For example, breast cancer incidence has been increasing, while mortality is going down. The rising mortality in people younger than 50 years is likely suggestive of more aggressive cancers being diagnosed — potentially secondary to environmental, dietary, or lifestyle factors. The colon is a unique organ because everything we put in our bodies passes through the colon, so food-based risk factors — for example, low fiber intake, red meat, and ultra-processed foods — are increasingly rising to the top as culprits.

Further, we know that only about 25% of people between the ages of 45 and 50 years are up to date with recommended colon cancer screenings, which can lead to later-stage diagnoses and thus higher mortality. So higher mortality speaks to the need to focus on lifestyle and diet changes and get more younger people to complete recommended cancer screenings.

Wagle: I think the “why” of your question is very important. Many researchers are trying to understand possible causes, such as diet, lifestyle, environmental factors, and genetics. But we cannot pinpoint one single cause. We need even more focus on research toward understanding the etiology of early-onset colorectal cancer.

What makes colorectal cancer different is that, unlike some other major cancers in this age group where mortality has declined despite rising incidence, roughly 3 in 4 colorectal cancers diagnosed in people younger than 50 years are [regional or distant], where the outcomes are worse.

Can you contextualize the rise in colorectal cancer mortality? What is the absolute rate among younger Americans now?

Wagle: It is around two deaths per 100,000 population in 2023 for people younger than 50 years. That number may not seem large, but the upward trend — a 1.1% annual increase from 2014 to 2023 — is concerning when you think about how overall mortality in this age group has dropped substantially over the past few decades. Colorectal cancer is moving in the opposite direction. I think the hopeful part is that it is also one of the most preventable cancers. Screening can stop cancer before it starts by removing precancerous polyps. Early-stage disease is highly treatable, and outcomes are better. That means better awareness and timely screening could make a real difference.

How can clinicians use this new information with regard to screening?

Wagle: For cancers with established screening guidelines, such as colorectal cancer, clinicians should continue to emphasize guideline-based screening and individualized risk assessment.

For colorectal cancer, screening now is recommended to start at age 45 for individuals at average risk, and earlier for [some], due to family history or other risk factors. Clinicians can use these findings to remind younger individuals that colorectal cancer is not only a disease of older adults and that screening at the recommended age can save lives.

In addition, red-flag symptoms such as persistent rectal bleeding, unexplained abdominal pain, difficulty in bowel movements, or signs of anemia should prompt appropriate evaluation in younger individuals.

Kamal: Clinicians should continue to emphasize timely completion of regular screening, starting at age 45 [for average-risk people]. Many still believe that the recommended starting age is 50 or that colonoscopy is the only way to get screened. Highlighting home-based screening options often helps patients make cancer screening logistically fit better into their busy lives.

Could you elaborate on the red-flag symptoms you mentioned, and what is an appropriate evaluation in younger individuals?

Kamal: Appropriate evaluation for any suspected bleeding — bright red or black and tarry — starts with an in-office evaluation by a primary care physician. Referral to a specialist, such as a gastroenterologist or surgeon, is done later, typically for direct visualization, such as with a colonoscopy. Rarely, imaging such as CT scans or ultrasounds is performed. Overall, because of the rising incidence of colon cancer in younger people, any concerning symptoms should be reported to a physician for an in-office evaluation as the first step.

Do these findings suggest that the starting age for average-risk people should be lowered—to age 40, for example?

Kamal: ACS screening guidelines for all cancers are part of an ongoing guideline development process by ACS scientists and volunteers. We monitor medical and scientific literature for new evidence that may support a change in current guidelines or the development of new guidelines and for information about cancer screening that should be conveyed to clinicians and target populations.

Keith Mulvihill is a freelance writer based in New York City.

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

First, the good news: Fewer Americans aged < 50 years are dying from cancer vs just a decade ago — reflecting progress in prevention, early detection, and treatment. There is, however, one big exception. Colorectal cancer mortality has been steadily inching up, and the disease now stands as the leading cause of cancer death in this age group, up from the fifth-leading in the early 1990s.

Those are the major findings of a recent study by the American Cancer Society (ACS), published as a research letter in JAMA.

Using SEER data, researchers found that the overall age-adjusted cancer death rate among Americans aged < 50 years dropped by 44% between 1990 and 2023 — from 25.5 to 14.2 per 100,000. And for 4 of the 5 leading causes of cancer death, there were mean annual declines from 2014 to 2023. The biggest change was in lung cancer deaths, which fell by an average of 5.7% per year. Meanwhile, leukemia and breast cancer deaths showed annual declines of 2.3% and 1.4%, respectively, despite rising incidences of both diseases among younger Americans.

The outlier is colorectal cancer, where mortality has been rising by about 1% per year since 2005. And it’s a pattern seen in both men and women.

Study coauthor Nikita Sandeep Wagle, PhD, MBBS, principal scientist, Cancer Surveillance Research at the ACS, and Arif Kamal, MD, ACS chief patient officer, discussed the research and its implications with Medscape Medical News.

Can you offer some possible reasons for the declining mortality in most of the cancers you studied?

Wagle: Mortality is going down for most of the cancers because we are getting better at finding cancers earlier and treating them more effectively. We have also seen improvements in screening, imaging, and therapy, and that means more people are being diagnosed at earlier stages and are surviving longer after diagnosis.

Regarding the rise in colorectal cancer mortality, do you think it's due to the rising incidence of early-onset colorectal cancer?

Kamal: Partially, but not completely, because the relationship between incidence and mortality is not always straightforward. For example, breast cancer incidence has been increasing, while mortality is going down. The rising mortality in people younger than 50 years is likely suggestive of more aggressive cancers being diagnosed — potentially secondary to environmental, dietary, or lifestyle factors. The colon is a unique organ because everything we put in our bodies passes through the colon, so food-based risk factors — for example, low fiber intake, red meat, and ultra-processed foods — are increasingly rising to the top as culprits.

Further, we know that only about 25% of people between the ages of 45 and 50 years are up to date with recommended colon cancer screenings, which can lead to later-stage diagnoses and thus higher mortality. So higher mortality speaks to the need to focus on lifestyle and diet changes and get more younger people to complete recommended cancer screenings.

Wagle: I think the “why” of your question is very important. Many researchers are trying to understand possible causes, such as diet, lifestyle, environmental factors, and genetics. But we cannot pinpoint one single cause. We need even more focus on research toward understanding the etiology of early-onset colorectal cancer.

What makes colorectal cancer different is that, unlike some other major cancers in this age group where mortality has declined despite rising incidence, roughly 3 in 4 colorectal cancers diagnosed in people younger than 50 years are [regional or distant], where the outcomes are worse.

Can you contextualize the rise in colorectal cancer mortality? What is the absolute rate among younger Americans now?

Wagle: It is around two deaths per 100,000 population in 2023 for people younger than 50 years. That number may not seem large, but the upward trend — a 1.1% annual increase from 2014 to 2023 — is concerning when you think about how overall mortality in this age group has dropped substantially over the past few decades. Colorectal cancer is moving in the opposite direction. I think the hopeful part is that it is also one of the most preventable cancers. Screening can stop cancer before it starts by removing precancerous polyps. Early-stage disease is highly treatable, and outcomes are better. That means better awareness and timely screening could make a real difference.

How can clinicians use this new information with regard to screening?

Wagle: For cancers with established screening guidelines, such as colorectal cancer, clinicians should continue to emphasize guideline-based screening and individualized risk assessment.

For colorectal cancer, screening now is recommended to start at age 45 for individuals at average risk, and earlier for [some], due to family history or other risk factors. Clinicians can use these findings to remind younger individuals that colorectal cancer is not only a disease of older adults and that screening at the recommended age can save lives.

In addition, red-flag symptoms such as persistent rectal bleeding, unexplained abdominal pain, difficulty in bowel movements, or signs of anemia should prompt appropriate evaluation in younger individuals.

Kamal: Clinicians should continue to emphasize timely completion of regular screening, starting at age 45 [for average-risk people]. Many still believe that the recommended starting age is 50 or that colonoscopy is the only way to get screened. Highlighting home-based screening options often helps patients make cancer screening logistically fit better into their busy lives.

Could you elaborate on the red-flag symptoms you mentioned, and what is an appropriate evaluation in younger individuals?

Kamal: Appropriate evaluation for any suspected bleeding — bright red or black and tarry — starts with an in-office evaluation by a primary care physician. Referral to a specialist, such as a gastroenterologist or surgeon, is done later, typically for direct visualization, such as with a colonoscopy. Rarely, imaging such as CT scans or ultrasounds is performed. Overall, because of the rising incidence of colon cancer in younger people, any concerning symptoms should be reported to a physician for an in-office evaluation as the first step.

Do these findings suggest that the starting age for average-risk people should be lowered—to age 40, for example?

Kamal: ACS screening guidelines for all cancers are part of an ongoing guideline development process by ACS scientists and volunteers. We monitor medical and scientific literature for new evidence that may support a change in current guidelines or the development of new guidelines and for information about cancer screening that should be conveyed to clinicians and target populations.

Keith Mulvihill is a freelance writer based in New York City.

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

First, the good news: Fewer Americans aged < 50 years are dying from cancer vs just a decade ago — reflecting progress in prevention, early detection, and treatment. There is, however, one big exception. Colorectal cancer mortality has been steadily inching up, and the disease now stands as the leading cause of cancer death in this age group, up from the fifth-leading in the early 1990s.

Those are the major findings of a recent study by the American Cancer Society (ACS), published as a research letter in JAMA.

Using SEER data, researchers found that the overall age-adjusted cancer death rate among Americans aged < 50 years dropped by 44% between 1990 and 2023 — from 25.5 to 14.2 per 100,000. And for 4 of the 5 leading causes of cancer death, there were mean annual declines from 2014 to 2023. The biggest change was in lung cancer deaths, which fell by an average of 5.7% per year. Meanwhile, leukemia and breast cancer deaths showed annual declines of 2.3% and 1.4%, respectively, despite rising incidences of both diseases among younger Americans.

The outlier is colorectal cancer, where mortality has been rising by about 1% per year since 2005. And it’s a pattern seen in both men and women.

Study coauthor Nikita Sandeep Wagle, PhD, MBBS, principal scientist, Cancer Surveillance Research at the ACS, and Arif Kamal, MD, ACS chief patient officer, discussed the research and its implications with Medscape Medical News.

Can you offer some possible reasons for the declining mortality in most of the cancers you studied?

Wagle: Mortality is going down for most of the cancers because we are getting better at finding cancers earlier and treating them more effectively. We have also seen improvements in screening, imaging, and therapy, and that means more people are being diagnosed at earlier stages and are surviving longer after diagnosis.

Regarding the rise in colorectal cancer mortality, do you think it's due to the rising incidence of early-onset colorectal cancer?

Kamal: Partially, but not completely, because the relationship between incidence and mortality is not always straightforward. For example, breast cancer incidence has been increasing, while mortality is going down. The rising mortality in people younger than 50 years is likely suggestive of more aggressive cancers being diagnosed — potentially secondary to environmental, dietary, or lifestyle factors. The colon is a unique organ because everything we put in our bodies passes through the colon, so food-based risk factors — for example, low fiber intake, red meat, and ultra-processed foods — are increasingly rising to the top as culprits.

Further, we know that only about 25% of people between the ages of 45 and 50 years are up to date with recommended colon cancer screenings, which can lead to later-stage diagnoses and thus higher mortality. So higher mortality speaks to the need to focus on lifestyle and diet changes and get more younger people to complete recommended cancer screenings.

Wagle: I think the “why” of your question is very important. Many researchers are trying to understand possible causes, such as diet, lifestyle, environmental factors, and genetics. But we cannot pinpoint one single cause. We need even more focus on research toward understanding the etiology of early-onset colorectal cancer.

What makes colorectal cancer different is that, unlike some other major cancers in this age group where mortality has declined despite rising incidence, roughly 3 in 4 colorectal cancers diagnosed in people younger than 50 years are [regional or distant], where the outcomes are worse.

Can you contextualize the rise in colorectal cancer mortality? What is the absolute rate among younger Americans now?

Wagle: It is around two deaths per 100,000 population in 2023 for people younger than 50 years. That number may not seem large, but the upward trend — a 1.1% annual increase from 2014 to 2023 — is concerning when you think about how overall mortality in this age group has dropped substantially over the past few decades. Colorectal cancer is moving in the opposite direction. I think the hopeful part is that it is also one of the most preventable cancers. Screening can stop cancer before it starts by removing precancerous polyps. Early-stage disease is highly treatable, and outcomes are better. That means better awareness and timely screening could make a real difference.

How can clinicians use this new information with regard to screening?

Wagle: For cancers with established screening guidelines, such as colorectal cancer, clinicians should continue to emphasize guideline-based screening and individualized risk assessment.

For colorectal cancer, screening now is recommended to start at age 45 for individuals at average risk, and earlier for [some], due to family history or other risk factors. Clinicians can use these findings to remind younger individuals that colorectal cancer is not only a disease of older adults and that screening at the recommended age can save lives.

In addition, red-flag symptoms such as persistent rectal bleeding, unexplained abdominal pain, difficulty in bowel movements, or signs of anemia should prompt appropriate evaluation in younger individuals.

Kamal: Clinicians should continue to emphasize timely completion of regular screening, starting at age 45 [for average-risk people]. Many still believe that the recommended starting age is 50 or that colonoscopy is the only way to get screened. Highlighting home-based screening options often helps patients make cancer screening logistically fit better into their busy lives.

Could you elaborate on the red-flag symptoms you mentioned, and what is an appropriate evaluation in younger individuals?

Kamal: Appropriate evaluation for any suspected bleeding — bright red or black and tarry — starts with an in-office evaluation by a primary care physician. Referral to a specialist, such as a gastroenterologist or surgeon, is done later, typically for direct visualization, such as with a colonoscopy. Rarely, imaging such as CT scans or ultrasounds is performed. Overall, because of the rising incidence of colon cancer in younger people, any concerning symptoms should be reported to a physician for an in-office evaluation as the first step.

Do these findings suggest that the starting age for average-risk people should be lowered—to age 40, for example?

Kamal: ACS screening guidelines for all cancers are part of an ongoing guideline development process by ACS scientists and volunteers. We monitor medical and scientific literature for new evidence that may support a change in current guidelines or the development of new guidelines and for information about cancer screening that should be conveyed to clinicians and target populations.

Keith Mulvihill is a freelance writer based in New York City.

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

TOPLINE:

An artificial intelligence (AI) model, developed using stool images, accurately assessed whether a patient’s bowel preparation was sufficient for colonoscopy. The best version of the model achieved an area under the receiver operating characteristic curve (AUC) of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86.

METHODOLOGY:

• Patients often need help during bowel preparation for colonoscopy, which increases staff workload; up to 20%-25% of colonoscopies are reported to be inadequately prepared. Researchers developed and tested an AI tool (AI-PREPOO) using stool images to assess whether patients were ready for colonoscopy.
• They conducted a multicenter observational study in Japan between 2022 and 2023 that included 37 patients scheduled for colonoscopy (median age, 57 years; 45.9% women).
• After starting consumption of a 2-liter polyethylene glycol solution, patients used smartphones to take photos of their stool in the toilet after each bowel movement and uploaded the images to a secure web server.
• The images were divided into training and test sets. Images were classified as “ready” for colonoscopy when the stool was clear or light yellow and watery with no solid content.
• Four image-recognition models based on different deep learning architectures were developed using transfer learning to classify readiness for colonoscopy.

TAKEAWAY:

• Researchers collected 282 stool images, with 141 classified as ready and 141 as not ready. Of these, 224 images were used for training (the number augmented to 2240 images) and 58 for testing.
• All four AI-PREPOO models showed high performance, with AUCs ranging from 0.92 to 0.95; pairwise differences in AUCs were not significant.
• The AI-PREPOO 1 model, based on the MobileNetV3-Small architecture, showed the most balanced performance, with an AUC of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86 on the test set.
• During colonoscopy, all patients had a Boston Bowel Preparation Scale score of 6 or higher, indicating that “ready” images corresponded to an adequately prepared bowel.

IN PRACTICE:

“If implemented as a mobile application, our model would allow patients to quickly and independently assess bowel preparation adequacy, reducing reliance on nurses and alleviating embarrassment associated with sharing stool images. This approach could also lessen nurses’ workload by minimizing unnecessary inquiries and preventing excessive or insufficient bowel preparation due to uncertainty,” the authors wrote.

SOURCE:

This study was led by Kosuke Kojima, Graduate School of Medical and Dental Sciences, Niigata University in Niigata, Japan. It was published online in the Journal of Gastroenterology and Hepatology.

LIMITATIONS:

The small dataset limited generalizability and increased the risk for overfitting. In real-world practice, stool images might vary in lighting, angle, focus, zoom, and background; thus, a larger and more diverse dataset was needed. The model lacked external validation in an independent or prospective cohort.

DISCLOSURES:

This study received support from the Japanese Foundation for Research and Promotion of Endoscopy. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

An artificial intelligence (AI) model, developed using stool images, accurately assessed whether a patient’s bowel preparation was sufficient for colonoscopy. The best version of the model achieved an area under the receiver operating characteristic curve (AUC) of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86.

METHODOLOGY:

• Patients often need help during bowel preparation for colonoscopy, which increases staff workload; up to 20%-25% of colonoscopies are reported to be inadequately prepared. Researchers developed and tested an AI tool (AI-PREPOO) using stool images to assess whether patients were ready for colonoscopy.
• They conducted a multicenter observational study in Japan between 2022 and 2023 that included 37 patients scheduled for colonoscopy (median age, 57 years; 45.9% women).
• After starting consumption of a 2-liter polyethylene glycol solution, patients used smartphones to take photos of their stool in the toilet after each bowel movement and uploaded the images to a secure web server.
• The images were divided into training and test sets. Images were classified as “ready” for colonoscopy when the stool was clear or light yellow and watery with no solid content.
• Four image-recognition models based on different deep learning architectures were developed using transfer learning to classify readiness for colonoscopy.

TAKEAWAY:

• Researchers collected 282 stool images, with 141 classified as ready and 141 as not ready. Of these, 224 images were used for training (the number augmented to 2240 images) and 58 for testing.
• All four AI-PREPOO models showed high performance, with AUCs ranging from 0.92 to 0.95; pairwise differences in AUCs were not significant.
• The AI-PREPOO 1 model, based on the MobileNetV3-Small architecture, showed the most balanced performance, with an AUC of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86 on the test set.
• During colonoscopy, all patients had a Boston Bowel Preparation Scale score of 6 or higher, indicating that “ready” images corresponded to an adequately prepared bowel.

IN PRACTICE:

“If implemented as a mobile application, our model would allow patients to quickly and independently assess bowel preparation adequacy, reducing reliance on nurses and alleviating embarrassment associated with sharing stool images. This approach could also lessen nurses’ workload by minimizing unnecessary inquiries and preventing excessive or insufficient bowel preparation due to uncertainty,” the authors wrote.

SOURCE:

This study was led by Kosuke Kojima, Graduate School of Medical and Dental Sciences, Niigata University in Niigata, Japan. It was published online in the Journal of Gastroenterology and Hepatology.

LIMITATIONS:

The small dataset limited generalizability and increased the risk for overfitting. In real-world practice, stool images might vary in lighting, angle, focus, zoom, and background; thus, a larger and more diverse dataset was needed. The model lacked external validation in an independent or prospective cohort.

DISCLOSURES:

This study received support from the Japanese Foundation for Research and Promotion of Endoscopy. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

An artificial intelligence (AI) model, developed using stool images, accurately assessed whether a patient’s bowel preparation was sufficient for colonoscopy. The best version of the model achieved an area under the receiver operating characteristic curve (AUC) of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86.

METHODOLOGY:

• Patients often need help during bowel preparation for colonoscopy, which increases staff workload; up to 20%-25% of colonoscopies are reported to be inadequately prepared. Researchers developed and tested an AI tool (AI-PREPOO) using stool images to assess whether patients were ready for colonoscopy.
• They conducted a multicenter observational study in Japan between 2022 and 2023 that included 37 patients scheduled for colonoscopy (median age, 57 years; 45.9% women).
• After starting consumption of a 2-liter polyethylene glycol solution, patients used smartphones to take photos of their stool in the toilet after each bowel movement and uploaded the images to a secure web server.
• The images were divided into training and test sets. Images were classified as “ready” for colonoscopy when the stool was clear or light yellow and watery with no solid content.
• Four image-recognition models based on different deep learning architectures were developed using transfer learning to classify readiness for colonoscopy.

TAKEAWAY:

• Researchers collected 282 stool images, with 141 classified as ready and 141 as not ready. Of these, 224 images were used for training (the number augmented to 2240 images) and 58 for testing.
• All four AI-PREPOO models showed high performance, with AUCs ranging from 0.92 to 0.95; pairwise differences in AUCs were not significant.
• The AI-PREPOO 1 model, based on the MobileNetV3-Small architecture, showed the most balanced performance, with an AUC of 0.95, accuracy of 0.90, sensitivity of 0.93, and specificity of 0.86 on the test set.
• During colonoscopy, all patients had a Boston Bowel Preparation Scale score of 6 or higher, indicating that “ready” images corresponded to an adequately prepared bowel.

IN PRACTICE:

“If implemented as a mobile application, our model would allow patients to quickly and independently assess bowel preparation adequacy, reducing reliance on nurses and alleviating embarrassment associated with sharing stool images. This approach could also lessen nurses’ workload by minimizing unnecessary inquiries and preventing excessive or insufficient bowel preparation due to uncertainty,” the authors wrote.

SOURCE:

This study was led by Kosuke Kojima, Graduate School of Medical and Dental Sciences, Niigata University in Niigata, Japan. It was published online in the Journal of Gastroenterology and Hepatology.

LIMITATIONS:

The small dataset limited generalizability and increased the risk for overfitting. In real-world practice, stool images might vary in lighting, angle, focus, zoom, and background; thus, a larger and more diverse dataset was needed. The model lacked external validation in an independent or prospective cohort.

DISCLOSURES:

This study received support from the Japanese Foundation for Research and Promotion of Endoscopy. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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.

TOPLINE:

Among patients with ulcerative colitis (UC) who develop colorectal cancer (CRC), greater background mucosal inflammation at the time of CRC diagnosis is associated with progressively worse survival outcomes, with tumors arising within the UC-involved segment having worse prognosis.

METHODOLOGY:

• Patients with UC are at an increased risk for CRC, with risk influenced by the extent and intensity of underlying mucosal inflammation.
• Researchers retrospectively reviewed medical records of patients with UC diagnosed with CRC between 1983 and 2020 at 43 institutions across Japan to determine whether inflammation at cancer diagnosis affected prognosis.
• After endoscopic assessment, tumors were classified as arising inside the UC‑involved segment at diagnosis (within‑area tumors) or outside that segment (outside‑area tumors).
• The Mayo endoscopic score (MES) was used to grade background mucosal inflammation in the within‑area group as inactive (MES 0), mild-moderate (MES 1-2), or severe (MES 3).
• The primary endpoint was 5-year recurrence-free survival, and the secondary endpoint was 5-year cancer-specific survival.

TAKEAWAY:

• Among 723 patients followed for a median of 51 months, 683 had within-area tumors (mean age at CRC diagnosis, 51.8 years; 61.9% male) and 40 had outside-area tumors (mean age at CRC diagnosis, 61.1 years; 60.0% male).
• The within-area group had lower rate of 5-year recurrence-free survival than the outside-area group (75.1% vs 87.6%; P = .022), and lower rate of 5-year cancer-specific survival (81.1% vs 94.3%; P = .038).
• Within-area tumor location independently predicted worse recurrence-free survival (adjusted hazard ratio, 2.99; P = .030).
• In the within‑area group, higher MES was associated with stepwise (although nonsignificant) declines in recurrence‑free survival (inactive, 84.4%; mild-moderate, 79.4%; severe, 73.8%; P = .150). Corresponding cancer‑specific survival rates in these groups declined significantly (89.0%, 84.8%, and 73.8%, respectively; P = .048).

IN PRACTICE:

“These findings shift the clinical focus from inflammation as a risk factor for carcinogenesis to inflammation as a prognostic determinant, highlighting a potential new role for systematic endoscopic assessment of the background mucosa at cancer diagnosis,” the authors wrote.

SOURCE:

This study was led by Akiyoshi Ikebata, Department of Surgery, Keio University School of Medicine, Tokyo, Japan. It was published online in December 2025, in the Journal of Crohn's and Colitis.

LIMITATIONS:

The retrospective design introduced potential for unmeasured confounding and selection bias. The MES was assigned by local physicians without central review, which may have introduced variability. The small size of the outside‑area tumor group increased the risk for baseline imbalances.

DISCLOSURES:

No specific funding source was reported. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Among patients with ulcerative colitis (UC) who develop colorectal cancer (CRC), greater background mucosal inflammation at the time of CRC diagnosis is associated with progressively worse survival outcomes, with tumors arising within the UC-involved segment having worse prognosis.

METHODOLOGY:

• Patients with UC are at an increased risk for CRC, with risk influenced by the extent and intensity of underlying mucosal inflammation.
• Researchers retrospectively reviewed medical records of patients with UC diagnosed with CRC between 1983 and 2020 at 43 institutions across Japan to determine whether inflammation at cancer diagnosis affected prognosis.
• After endoscopic assessment, tumors were classified as arising inside the UC‑involved segment at diagnosis (within‑area tumors) or outside that segment (outside‑area tumors).
• The Mayo endoscopic score (MES) was used to grade background mucosal inflammation in the within‑area group as inactive (MES 0), mild-moderate (MES 1-2), or severe (MES 3).
• The primary endpoint was 5-year recurrence-free survival, and the secondary endpoint was 5-year cancer-specific survival.

TAKEAWAY:

• Among 723 patients followed for a median of 51 months, 683 had within-area tumors (mean age at CRC diagnosis, 51.8 years; 61.9% male) and 40 had outside-area tumors (mean age at CRC diagnosis, 61.1 years; 60.0% male).
• The within-area group had lower rate of 5-year recurrence-free survival than the outside-area group (75.1% vs 87.6%; P = .022), and lower rate of 5-year cancer-specific survival (81.1% vs 94.3%; P = .038).
• Within-area tumor location independently predicted worse recurrence-free survival (adjusted hazard ratio, 2.99; P = .030).
• In the within‑area group, higher MES was associated with stepwise (although nonsignificant) declines in recurrence‑free survival (inactive, 84.4%; mild-moderate, 79.4%; severe, 73.8%; P = .150). Corresponding cancer‑specific survival rates in these groups declined significantly (89.0%, 84.8%, and 73.8%, respectively; P = .048).

IN PRACTICE:

“These findings shift the clinical focus from inflammation as a risk factor for carcinogenesis to inflammation as a prognostic determinant, highlighting a potential new role for systematic endoscopic assessment of the background mucosa at cancer diagnosis,” the authors wrote.

SOURCE:

This study was led by Akiyoshi Ikebata, Department of Surgery, Keio University School of Medicine, Tokyo, Japan. It was published online in December 2025, in the Journal of Crohn's and Colitis.

LIMITATIONS:

The retrospective design introduced potential for unmeasured confounding and selection bias. The MES was assigned by local physicians without central review, which may have introduced variability. The small size of the outside‑area tumor group increased the risk for baseline imbalances.

DISCLOSURES:

No specific funding source was reported. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Among patients with ulcerative colitis (UC) who develop colorectal cancer (CRC), greater background mucosal inflammation at the time of CRC diagnosis is associated with progressively worse survival outcomes, with tumors arising within the UC-involved segment having worse prognosis.

METHODOLOGY:

• Patients with UC are at an increased risk for CRC, with risk influenced by the extent and intensity of underlying mucosal inflammation.
• Researchers retrospectively reviewed medical records of patients with UC diagnosed with CRC between 1983 and 2020 at 43 institutions across Japan to determine whether inflammation at cancer diagnosis affected prognosis.
• After endoscopic assessment, tumors were classified as arising inside the UC‑involved segment at diagnosis (within‑area tumors) or outside that segment (outside‑area tumors).
• The Mayo endoscopic score (MES) was used to grade background mucosal inflammation in the within‑area group as inactive (MES 0), mild-moderate (MES 1-2), or severe (MES 3).
• The primary endpoint was 5-year recurrence-free survival, and the secondary endpoint was 5-year cancer-specific survival.

TAKEAWAY:

• Among 723 patients followed for a median of 51 months, 683 had within-area tumors (mean age at CRC diagnosis, 51.8 years; 61.9% male) and 40 had outside-area tumors (mean age at CRC diagnosis, 61.1 years; 60.0% male).
• The within-area group had lower rate of 5-year recurrence-free survival than the outside-area group (75.1% vs 87.6%; P = .022), and lower rate of 5-year cancer-specific survival (81.1% vs 94.3%; P = .038).
• Within-area tumor location independently predicted worse recurrence-free survival (adjusted hazard ratio, 2.99; P = .030).
• In the within‑area group, higher MES was associated with stepwise (although nonsignificant) declines in recurrence‑free survival (inactive, 84.4%; mild-moderate, 79.4%; severe, 73.8%; P = .150). Corresponding cancer‑specific survival rates in these groups declined significantly (89.0%, 84.8%, and 73.8%, respectively; P = .048).

IN PRACTICE:

“These findings shift the clinical focus from inflammation as a risk factor for carcinogenesis to inflammation as a prognostic determinant, highlighting a potential new role for systematic endoscopic assessment of the background mucosa at cancer diagnosis,” the authors wrote.

SOURCE:

This study was led by Akiyoshi Ikebata, Department of Surgery, Keio University School of Medicine, Tokyo, Japan. It was published online in December 2025, in the Journal of Crohn's and Colitis.

LIMITATIONS:

The retrospective design introduced potential for unmeasured confounding and selection bias. The MES was assigned by local physicians without central review, which may have introduced variability. The small size of the outside‑area tumor group increased the risk for baseline imbalances.

DISCLOSURES:

No specific funding source was reported. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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