Colon and Rectal

This transcript has been edited for clarity.

New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we’re still seeing advanced cancer in younger patients who haven’t been screened in time. 

Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, “What can I do now to help myself?” 

Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let’s take a closer look at the results.

 

Exercise’s Risk Reduction Potential

The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep. 

A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. 

Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. 

The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.

Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise. 

The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.

At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% (P = .02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively. 

Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise. 

There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it’s unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group. 

But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.

 

Adjuvant Aspirin in Colon Cancer Subset

That’s a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.

The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). 

PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression. 

Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery. 

Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years (P = .044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction. 

There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160-mg use in the current study is fairly normal, roughly equivalent to two low-dose (81-mg) aspirin tablets. 

Now, it’s worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Services Task Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach. 

 

Two Proactive Actions

These studies highlight 2 interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring. 

Exercise is broadly beneficial and can be recommended immediately. 

For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most. 

These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.

Johnson is a regular contributor to Medscape. He is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He disclosed that he is an adviser for ISOThrive. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we’re still seeing advanced cancer in younger patients who haven’t been screened in time. 

Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, “What can I do now to help myself?” 

Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let’s take a closer look at the results.

 

Exercise’s Risk Reduction Potential

The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep. 

A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. 

Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. 

The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.

Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise. 

The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.

At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% (P = .02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively. 

Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise. 

There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it’s unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group. 

But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.

 

Adjuvant Aspirin in Colon Cancer Subset

That’s a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.

The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). 

PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression. 

Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery. 

Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years (P = .044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction. 

There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160-mg use in the current study is fairly normal, roughly equivalent to two low-dose (81-mg) aspirin tablets. 

Now, it’s worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Services Task Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach. 

 

Two Proactive Actions

These studies highlight 2 interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring. 

Exercise is broadly beneficial and can be recommended immediately. 

For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most. 

These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.

Johnson is a regular contributor to Medscape. He is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He disclosed that he is an adviser for ISOThrive. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we’re still seeing advanced cancer in younger patients who haven’t been screened in time. 

Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, “What can I do now to help myself?” 

Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let’s take a closer look at the results.

 

Exercise’s Risk Reduction Potential

The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep. 

A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease. 

Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period. 

The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.

Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise. 

The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.

At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% (P = .02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively. 

Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise. 

There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it’s unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group. 

But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.

 

Adjuvant Aspirin in Colon Cancer Subset

That’s a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.

The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha). 

PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression. 

Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery. 

Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years (P = .044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction. 

There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160-mg use in the current study is fairly normal, roughly equivalent to two low-dose (81-mg) aspirin tablets. 

Now, it’s worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Services Task Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach. 

 

Two Proactive Actions

These studies highlight 2 interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring. 

Exercise is broadly beneficial and can be recommended immediately. 

For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most. 

These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.

Johnson is a regular contributor to Medscape. He is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He disclosed that he is an adviser for ISOThrive. 

A version of this article appeared on Medscape.com.

The risk of detecting colorectal cancer (CRC) increases by up to 13-fold in the presence of prior fecal hemoglobin (f-Hb) concentrations in fecal immunochemical tests (FIT), especially negative ones, according to a large international dose-response meta-analysis.

Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”

Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. 

Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.

According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.

 

Study Details

The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.

All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.

With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I² = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.

“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the United States report as a qualitative positive-negative result.”

The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.

Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.

 

Feasibility of Implementation

In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.

“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.

Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.

The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.

This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing. The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.

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

The risk of detecting colorectal cancer (CRC) increases by up to 13-fold in the presence of prior fecal hemoglobin (f-Hb) concentrations in fecal immunochemical tests (FIT), especially negative ones, according to a large international dose-response meta-analysis.

Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”

Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. 

Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.

According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.

 

Study Details

The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.

All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.

With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I² = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.

“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the United States report as a qualitative positive-negative result.”

The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.

Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.

 

Feasibility of Implementation

In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.

“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.

Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.

The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.

This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing. The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.

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

The risk of detecting colorectal cancer (CRC) increases by up to 13-fold in the presence of prior fecal hemoglobin (f-Hb) concentrations in fecal immunochemical tests (FIT), especially negative ones, according to a large international dose-response meta-analysis.

Although the association with neoplasia decreased as f-Hb levels rose, the findings support the development of risk-stratified screening strategies based on these concentrations, according to researchers led by Danica M.N. van den Berg, MSc, a PhD candidate and econometrics researcher in the department of public health at Erasmus University Medical Center in Rotterdam, the Netherlands.

Higher f-Hb concentrations in prior negative screening tests are strongly associated with an increased risk of detecting colorectal neoplasia in subsequent screenings, van den Berg said in an interview. “Gastroenterologists and other clinicians should consider the value of f-Hb concentrations in refining screening protocols and personalizing patient care to detect colorectal neoplasia earlier and more accurately.”

Published in Gastroenterology, the study was prompted by prior research showing individuals with f-Hb concentrations just below the positivity cutoff had an elevated CRC risk vs those with low or no f-Hb. “However, global variations in FIT positivity cutoffs and f-Hb category definitions complicated cross-study comparisons,” van den Berg said. 

Given the lack of an established dose-response relationship, the study aimed to clarify how f-Hb levels in previous screenings correlate with colorectal neoplasia detection. “Understanding this relationship is crucial for developing risk-stratified colorectal cancer screening strategies based on prior FIT results, which could improve the harm-benefit balance of screening,” she said.

According to van den Berg, f-Hb concentrations could help determine optimal CRC screening intervals by identifying higher-risk individuals who could benefit from more frequent testing, while those with lower concentrations could be screened less frequently.

 

Study Details

The systematic review and meta-analysis are the first to focus on the dose-response relationship between f-Hb levels in prior FIT screenings and colorectal neoplasia detection, van den Berg said. It included 13 ethnically diverse studies published during 2011-2023 with 4,493,223 individuals from Spain, France, the Netherlands, Taiwan, Denmark, Scotland, Ireland, Korea, Italy, and Norway. Most studies were cohort-based, and one was a randomized controlled trial.

All studies demonstrated a positive association between f-Hb in previous screenings and colorectal neoplasia detection. Almost all reported the f-Hb concentration measured in the prior screening round, while one study combined the f-Hb concentration of two previous screening rounds by using the cumulative f-Hb value. There was, however, wide variability in the stool positivity cut-offs in the included studies, ranging from 10 μg f-Hb/g to 80 μg f-Hb/g.

With an overall effect size of 0.69 (95% CI, 0.59-0.79), pooled analysis revealed that in the next screening round, individuals with f-Hb concentrations in stool of 5, 10, 20, and 40 μg/g had a threefold, fivefold, eightfold, and 13-fold higher risk for colorectal neoplasia, respectively, vs individuals showing 0 μg/g. Although there was significant study heterogeneity (I² = 97.5%, P < .001), sensitivity analyses confirmed the consistency of findings. Interestingly, subgroup analyses indicated that f-Hb concentrations from a previous negative test were especially predictive of advanced neoplasia in subsequent screenings.

“This is a strategy worth pursuing and evaluating in the United States,” said gastroenterologist Theodore R. Levin, MD, a research scientist at Kaiser Permanente Division of Research in Northern California, commenting on the study but not involved in it. “However, there is no currently available FIT brand in the US that reports f-Hb concentration. All FITs in the United States report as a qualitative positive-negative result.”

The Dutch investigation aligns with prior studies demonstrating a positive association between f-Hb concentrations in previous screenings and the detection of colorectal neoplasia. “Our working hypothesis was that risk increases in a decreasing manner as f-Hb concentrations rise, and the findings supported this hypothesis,” van den Berg said.

Other research has projected f-Hb level risk stratification to be effective and perhaps cost-effective in reducing delayed diagnosis of CRC.

 

Feasibility of Implementation

In large national screening programs in Europe, Asia, and Australia, as well as those of Kaiser Permanente and the Veterans Health Administration in the United States, information on f-Hb concentrations is already available.

“Therefore, incorporating an Hb-based approach should be relatively easy and affordable,” van den Berg said, and may help to optimize resource use while maintaining high detection rates. “However, the more critical question is whether such an approach would be acceptable to the target population.” To that end, randomized controlled trials in Italy and the Netherlands are offering tailored invitation intervals based on prior f-Hb concentrations and may provide insight into the real-world application of risk-stratified screening.

Among the many variables to be considered in the context of population-wide screening are cost-effectiveness, acceptability, and practicality, as well as invitation intervals, positivity cut-off levels, and start and stop ages for screening. “A key focus will be understanding the acceptability of risk-stratified colorectal cancer screening based on f-Hb among the target population and addressing any information needs they may have, as these are critical factors for successful implementation,” said van den Berg. Her group is currently studying the most effective and cost-effective risk-based strategy for CRC screening based on f-Hb levels.

The authors cautioned that since individuals with undetectable f-Hb levels make up the majority of those with negative FIT results, care must be taken that reducing screening frequency for this low-risk group does not lead to unfavorable outcomes at the population level.

This study was funded by the Dutch Organization for Scientific Research, which had no role in study design, data collection, analysis, interpretation, or writing. The authors declared no competing interests. Levin disclosed no competing interests relevant to his comments.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

• Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
• The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
• A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
• The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

• Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
• Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
• Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
• Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. 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. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

• Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
• The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
• A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
• The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

• Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
• Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
• Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
• Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. 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. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

• Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
• The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
• A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
• The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

• Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
• Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
• Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
• Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. 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. A version of this article first appeared on Medscape.com.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant 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:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant 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:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant 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.