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Gut microbiome variations may be predictive of precancerous colonic lesions, CRC
COPENHAGEN – according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.
The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.
“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.
The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.
In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.
“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%.
“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
Longitudinal analysis using large Dutch databases
To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.
They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.
“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained.
The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
More precancerous lesions found after fecal sampling
There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.
Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.
When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.
The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.
“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.
Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.
“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
More time needed
Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.
“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”
He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.”
However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.
Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COPENHAGEN – according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.
The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.
“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.
The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.
In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.
“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%.
“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
Longitudinal analysis using large Dutch databases
To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.
They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.
“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained.
The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
More precancerous lesions found after fecal sampling
There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.
Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.
When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.
The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.
“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.
Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.
“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
More time needed
Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.
“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”
He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.”
However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.
Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COPENHAGEN – according to a large, 22-year analysis from the Dutch Microbiome Project cohort study.
The findings suggest a possible role for gut microbiota in the development of colorectal lesions and cancer, said study lead Ranko Gacesa, PhD, from the department of gastroenterology, University of Groningen (the Netherlands), who presented the results at the annual United European Gastroenterology Week.
“It [also] suggests that gut bacteria might enhance currently used noninvasive fecal tests for the detection of colorectal polyps, and even that microbiome-modulating therapies might play a role in prevention of colorectal cancer,” said Dr. Gacesa, who won the award for best abstract in the meeting session.
The gut microbiome is known to be linked to colorectal cancer (CRC); in particular, the bacteria Bacteroides fragilis and Alistipes finegoldii have been found to cause CRC in mouse models, explained Dr. Gacesa.
In the current study, Dr. Gacesa and colleagues looked at the potential for the gut microbiome in humans to play a role in the detection of precancerous colonic lesions. The noninvasive fecal immunochemical test (FIT), recently shown to be a preference among patients, produces a high number of false-positive results, leading to many unnecessary colonoscopies.
“It has been calculated that the use of a fecal microbiota analysis combined with FIT in the early-stage prediction of CRC could result in a high true-positive rate and a low false-positive rate,” said Dr. Gacesa. “In this way, we might reduce the false-positive rate by around 50%.
“Ideally, we don’t want to detect cancer when it is already established and is hard to treat. We want to detect it as early in its development as possible,” he said.
Longitudinal analysis using large Dutch databases
To determine the direction of the relationship between CRC and the gut microbiome, the Dutch researchers conducted a longitudinal analysis from 2000 to 2022, looking at whether CRC alters the gut microbiome, as well as whether changes in the microbiome contribute to the development of precancerous lesions and CRC.
They drew on data from the Dutch colorectal cancer screening program, comprising FIT results in people aged 55 years and older, and colonoscopy if referred. They recorded cases of colonic biopsies from the extensive Dutch national database of medical biopsies. These were then linked with Dutch microbiome project data sourced from fecal samples of 8208 individuals taken between 2012 and 2015.
“This allowed us to associate gut microbiome compositions and functions to detailed histological information about precancerous lesions and CRC, including when lesions were detected relative to fecal sampling [and a reading of the gut microbiome],” Dr. Gacesa explained.
The analysis determined the composition, function, and genomic profiles of gut microbiota in participants who developed precancerous colorectal lesions before fecal sampling from 2000 to 2015, and in those participants who developed lesions after fecal sampling, between 2015 and 2022. Clinical phenotypes, comprising the type and size of lesions, were noted. The control group included 2123 individuals from the general population with normal colonoscopy findings.
More precancerous lesions found after fecal sampling
There were more cases of precancerous lesions found after fecal sampling, reported Dr. Gacesa.
Before fecal sampling, 219 participants had colonic lesions, including low-grade dysplasia, high-grade dysplasia, and serrated polyps, and 26 cases of CRC. A total of 315 participants developed assorted colonic lesions after fecal sampling, with a total of 29 cases of CRC.
When the researchers looked at microbiome diversity in people who had experienced precancerous colonic lesions 1-5 years before fecal sampling, they found that diversity was lower, compared with controls. Microbiome diversity was also decreased in participants who developed colonic lesions after sampling.
The microbiome composition and function were different between patients with preexisting and future lesions, and varied based on the types of lesion.
“We saw a drop in some commensal bacteria, including Faecalibacterium, in both those with recent pathologies and those who developed them in the future. We also saw a massive spike in Alistipes finegoldii in those who had CRC, strongly suggesting it is closely linked to CRC in people,” reported Dr. Gacesa.
Among bacterial species linked with the future development of precancerous lesions were those from the family of Lachnospiraceae, and the genera Roseburia and Eubacterium. Microbiome composition had a moderate predictive power for future lesions and CRC.
“Precancerous lesions are linked to the gut microbiome,” Dr. Gacesa said. “Adenomas – both preexisting ones (before fecal sampling), and ones that came after fecal sampling – are significantly linked to the microbiome composition.”
More time needed
Loris Lopetuso, MD, gastroenterologist, from Fondazione Policlinico Universitario Agostino Gemelli, Rome, who comoderated the session, remarked that the data were intriguing and important.
“We really need to find new predictors of tumorigenesis,” he said. “We already have some good predictors, mainly FIT, but these are not enough. These gut microbiota look promising.”
He added that the study by Dr. Gacesa’s team was one of the largest he had seen. “But I would note that, methodologically, we need to remember that the time between a fecal sample and the development of polyps can be very large,” Dr. Lopetuso emphasized. “This study looked at around 5 years only. Also, the microbiota can change from one day to the other in response to stress, diet, and many other things.”
However, “this could be the beginning of a longitudinal study between cases and controls because many years are needed,” he added.
Dr. Gacesa has received funding from Janssen Pharmaceuticals for an unrelated research project. He is a paid R&D consultant for Esox Biologics Ltd for topics unrelated to this project. Dr. Lopetuso reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT UEG 2023
This tool can predict recurrence in rectal cancer watchful waiting
TOPLINE:
for both local regrowth and distant metastasis during watchful waiting.
METHODOLOGY:
- Currently, oncologists do not have a biomarker that can help select patients with rectal cancer for watchful waiting after neoadjuvant chemoradiotherapy as well as help monitor them over time. And about 25% of patients on watchful waiting will eventually relapse.
- The Immunoscore biopsy quantifies the degree of immune infiltration on pretreatment tumor biopsies, looking at the density of CD3- and CD8-positive T cells at baseline, given that greater infiltration has been associated with prolonged treatment response.
- To determine whether the Immunoscore can help select patients for watchful waiting, investigators correlated Immunoscore with time to recurrence in 249 patients with stage I-III rectal cancer who were undergoing watchful waiting after complete clinical responses to neoadjuvant chemoradiotherapy.
- CD3- and CD8-positive T-cell densities were converted into percentiles and then translated into scores of Immunoscore biopsy: low (0%-25%), intermediate (> 25%-70%), and high (> 70%-100%).
TAKEAWAY:
- The Immunoscore biopsy significantly improved predictions of recurrence: 5-year recurrence-free survival was 91.3% among patients with high scores, 62.5% among those with intermediate scores, and 53.1% among those with low scores.
- The Immunoscore was significantly associated with disease-free survival (log-rank P = .0002) and predicted both local regrowth and distant metastasis.
- On multivariate analysis, the Immunoscore’s predictive ability was independent of age, sex, tumor location, cT stage, and cN stage, and was the strongest predictor of time to recurrence (hazard ratio, high vs. low, 6.93; P = .0017).
IN PRACTICE:
This validation study confirms that the Immunoscore biopsy “is an independent parameter predicting time to recurrence” and can help physicians and patients decide whether to opt for watchful waiting, the study authors wrote.
SOURCE:
The study, led by Carine El Sissy of the Laboratory of Integrative Cancer Immunology, Paris, was published Oct. 3 in the Journal of Clinical Oncology.
LIMITATIONS:
Mismatch repair gene expression status was not assessed.
DISCLOSURES:
The work was supported by the L’Institut National de la Santé et de la Recherche Médicale and others. Investigators disclosed patents related to the work and ties to many companies, including Amgen, AstraZeneca, and Merck. One investigator is an employee of Novo Nordisk, and another is employed by Veracyte.
A version of this article first appeared on Medscape.com.
TOPLINE:
for both local regrowth and distant metastasis during watchful waiting.
METHODOLOGY:
- Currently, oncologists do not have a biomarker that can help select patients with rectal cancer for watchful waiting after neoadjuvant chemoradiotherapy as well as help monitor them over time. And about 25% of patients on watchful waiting will eventually relapse.
- The Immunoscore biopsy quantifies the degree of immune infiltration on pretreatment tumor biopsies, looking at the density of CD3- and CD8-positive T cells at baseline, given that greater infiltration has been associated with prolonged treatment response.
- To determine whether the Immunoscore can help select patients for watchful waiting, investigators correlated Immunoscore with time to recurrence in 249 patients with stage I-III rectal cancer who were undergoing watchful waiting after complete clinical responses to neoadjuvant chemoradiotherapy.
- CD3- and CD8-positive T-cell densities were converted into percentiles and then translated into scores of Immunoscore biopsy: low (0%-25%), intermediate (> 25%-70%), and high (> 70%-100%).
TAKEAWAY:
- The Immunoscore biopsy significantly improved predictions of recurrence: 5-year recurrence-free survival was 91.3% among patients with high scores, 62.5% among those with intermediate scores, and 53.1% among those with low scores.
- The Immunoscore was significantly associated with disease-free survival (log-rank P = .0002) and predicted both local regrowth and distant metastasis.
- On multivariate analysis, the Immunoscore’s predictive ability was independent of age, sex, tumor location, cT stage, and cN stage, and was the strongest predictor of time to recurrence (hazard ratio, high vs. low, 6.93; P = .0017).
IN PRACTICE:
This validation study confirms that the Immunoscore biopsy “is an independent parameter predicting time to recurrence” and can help physicians and patients decide whether to opt for watchful waiting, the study authors wrote.
SOURCE:
The study, led by Carine El Sissy of the Laboratory of Integrative Cancer Immunology, Paris, was published Oct. 3 in the Journal of Clinical Oncology.
LIMITATIONS:
Mismatch repair gene expression status was not assessed.
DISCLOSURES:
The work was supported by the L’Institut National de la Santé et de la Recherche Médicale and others. Investigators disclosed patents related to the work and ties to many companies, including Amgen, AstraZeneca, and Merck. One investigator is an employee of Novo Nordisk, and another is employed by Veracyte.
A version of this article first appeared on Medscape.com.
TOPLINE:
for both local regrowth and distant metastasis during watchful waiting.
METHODOLOGY:
- Currently, oncologists do not have a biomarker that can help select patients with rectal cancer for watchful waiting after neoadjuvant chemoradiotherapy as well as help monitor them over time. And about 25% of patients on watchful waiting will eventually relapse.
- The Immunoscore biopsy quantifies the degree of immune infiltration on pretreatment tumor biopsies, looking at the density of CD3- and CD8-positive T cells at baseline, given that greater infiltration has been associated with prolonged treatment response.
- To determine whether the Immunoscore can help select patients for watchful waiting, investigators correlated Immunoscore with time to recurrence in 249 patients with stage I-III rectal cancer who were undergoing watchful waiting after complete clinical responses to neoadjuvant chemoradiotherapy.
- CD3- and CD8-positive T-cell densities were converted into percentiles and then translated into scores of Immunoscore biopsy: low (0%-25%), intermediate (> 25%-70%), and high (> 70%-100%).
TAKEAWAY:
- The Immunoscore biopsy significantly improved predictions of recurrence: 5-year recurrence-free survival was 91.3% among patients with high scores, 62.5% among those with intermediate scores, and 53.1% among those with low scores.
- The Immunoscore was significantly associated with disease-free survival (log-rank P = .0002) and predicted both local regrowth and distant metastasis.
- On multivariate analysis, the Immunoscore’s predictive ability was independent of age, sex, tumor location, cT stage, and cN stage, and was the strongest predictor of time to recurrence (hazard ratio, high vs. low, 6.93; P = .0017).
IN PRACTICE:
This validation study confirms that the Immunoscore biopsy “is an independent parameter predicting time to recurrence” and can help physicians and patients decide whether to opt for watchful waiting, the study authors wrote.
SOURCE:
The study, led by Carine El Sissy of the Laboratory of Integrative Cancer Immunology, Paris, was published Oct. 3 in the Journal of Clinical Oncology.
LIMITATIONS:
Mismatch repair gene expression status was not assessed.
DISCLOSURES:
The work was supported by the L’Institut National de la Santé et de la Recherche Médicale and others. Investigators disclosed patents related to the work and ties to many companies, including Amgen, AstraZeneca, and Merck. One investigator is an employee of Novo Nordisk, and another is employed by Veracyte.
A version of this article first appeared on Medscape.com.
Does diabetes affect colorectal cancer outcomes?
TOPLINE:
, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.
METHODOLOGY:
- This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
- The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
- The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
TAKEAWAY:
- Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
- Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
- Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
- Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.
IN PRACTICE:
“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.
SOURCE:
The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.
LIMITATIONS:
Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.
DISCLOSURES:
Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.
METHODOLOGY:
- This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
- The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
- The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
TAKEAWAY:
- Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
- Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
- Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
- Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.
IN PRACTICE:
“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.
SOURCE:
The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.
LIMITATIONS:
Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.
DISCLOSURES:
Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.
METHODOLOGY:
- This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
- The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
- The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
TAKEAWAY:
- Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
- Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
- Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
- Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.
IN PRACTICE:
“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.
SOURCE:
The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.
LIMITATIONS:
Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.
DISCLOSURES:
Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Breastfeeding and colorectal cancer
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Two multitarget stool tests show promise for CRC screening: Studies
VANCOUVER –
In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.
In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.
Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
RNA as a biomarker
For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.
The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.
Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.
The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.
Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.
The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.
“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.
Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.
Results also were reliable across all ages.
“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.
RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
Detection by DNA
Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.
The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.
Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.
Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.
Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).
Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).
In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).
The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.
Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.
“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
Tests to provide more noninvasive options
Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”
While we will have to wait for the full publications, U.S. Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Dr. Shaukat, professor of medicine and population health at NYU Langone Health, New York, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.
These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.
“We are always looking for ways to increase colon cancer screening uptake,” said Brooks Cash, MD, professor and chief of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, who also was not affiliated with the research.
Certainly, the multitarget stool DNA is not a new concept with Cologuard, but it is a new assay, Dr. Cash said.
“It’s significantly different than their previous version, and they were able to show improved sensitivity as well as specificity, which has been one of the concerns,” he said.
The multitarget stool RNA test “shows very similar results,” Dr. Cash added. “Their predicate is that it’s slightly different and actually may return very good sensitivity for older patients, where you don’t have the same methylation issues with the DNA.”
“It will be interesting to see how they play out,” he added.
“The critical part to all of these tests is that if a patient has a positive test, they need to get a colonoscopy. That doesn’t always happen,” Dr. Cash said. “We have to make sure that there’s appropriate education for not only patients but also providers, many of whom will not be gastroenterologists.”
Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Dr. Lieberman is an advisor or review panel member for Geneoscopy. Dr. Imperiale receives grant or research support from Exact Sciences. Dr. Shaukat reports no relevant financial relationships. Dr. Cash is on the advisory board for Exact Sciences.
A version of this article first appeared on Medscape.com.
VANCOUVER –
In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.
In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.
Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
RNA as a biomarker
For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.
The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.
Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.
The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.
Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.
The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.
“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.
Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.
Results also were reliable across all ages.
“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.
RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
Detection by DNA
Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.
The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.
Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.
Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.
Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).
Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).
In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).
The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.
Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.
“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
Tests to provide more noninvasive options
Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”
While we will have to wait for the full publications, U.S. Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Dr. Shaukat, professor of medicine and population health at NYU Langone Health, New York, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.
These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.
“We are always looking for ways to increase colon cancer screening uptake,” said Brooks Cash, MD, professor and chief of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, who also was not affiliated with the research.
Certainly, the multitarget stool DNA is not a new concept with Cologuard, but it is a new assay, Dr. Cash said.
“It’s significantly different than their previous version, and they were able to show improved sensitivity as well as specificity, which has been one of the concerns,” he said.
The multitarget stool RNA test “shows very similar results,” Dr. Cash added. “Their predicate is that it’s slightly different and actually may return very good sensitivity for older patients, where you don’t have the same methylation issues with the DNA.”
“It will be interesting to see how they play out,” he added.
“The critical part to all of these tests is that if a patient has a positive test, they need to get a colonoscopy. That doesn’t always happen,” Dr. Cash said. “We have to make sure that there’s appropriate education for not only patients but also providers, many of whom will not be gastroenterologists.”
Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Dr. Lieberman is an advisor or review panel member for Geneoscopy. Dr. Imperiale receives grant or research support from Exact Sciences. Dr. Shaukat reports no relevant financial relationships. Dr. Cash is on the advisory board for Exact Sciences.
A version of this article first appeared on Medscape.com.
VANCOUVER –
In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.
In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.
Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
RNA as a biomarker
For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.
The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.
Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.
The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.
Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.
The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.
“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.
Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.
Results also were reliable across all ages.
“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.
RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
Detection by DNA
Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.
The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.
Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.
Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.
Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).
Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).
In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).
The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.
Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.
“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
Tests to provide more noninvasive options
Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”
While we will have to wait for the full publications, U.S. Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Dr. Shaukat, professor of medicine and population health at NYU Langone Health, New York, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.
These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.
“We are always looking for ways to increase colon cancer screening uptake,” said Brooks Cash, MD, professor and chief of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, who also was not affiliated with the research.
Certainly, the multitarget stool DNA is not a new concept with Cologuard, but it is a new assay, Dr. Cash said.
“It’s significantly different than their previous version, and they were able to show improved sensitivity as well as specificity, which has been one of the concerns,” he said.
The multitarget stool RNA test “shows very similar results,” Dr. Cash added. “Their predicate is that it’s slightly different and actually may return very good sensitivity for older patients, where you don’t have the same methylation issues with the DNA.”
“It will be interesting to see how they play out,” he added.
“The critical part to all of these tests is that if a patient has a positive test, they need to get a colonoscopy. That doesn’t always happen,” Dr. Cash said. “We have to make sure that there’s appropriate education for not only patients but also providers, many of whom will not be gastroenterologists.”
Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Dr. Lieberman is an advisor or review panel member for Geneoscopy. Dr. Imperiale receives grant or research support from Exact Sciences. Dr. Shaukat reports no relevant financial relationships. Dr. Cash is on the advisory board for Exact Sciences.
A version of this article first appeared on Medscape.com.
AT ACG 2023
Study reveals potentially unnecessary CRC screening in older adults
TOPLINE:
Older adults with limited life expectancy are just as likely to undergo colorectal cancer (CRC) screening as those with longer life expectancy, a new study shows.
METHODOLOGY:
- Researchers used national survey data to estimate the prevalence and factors associated with CRC screening in 25,888 community-dwelling adults aged 65-84 according to their predicted 10-year mortality risk.
- They estimated 10-year mortality risk using a validated index. From the lowest to highest quintiles, mortality risk was 12%, 24%, 39%, 58%, and 79%, respectively.
- Investigators determined the proportion of screening performed in adults with life expectancy less than 10 years, defined as 10-year mortality risk ≥ 50% (that is, quintiles 4 and 5).
TAKEAWAY:
- In this cohort of older adults previously not up to date with CRC screening, the overall prevalence of past-year screening was 38.5%.
- The prevalence of past-year CRC screening decreased with advancing age but did not differ significantly by 10-year mortality risk. From lowest to highest quintile, prevalence was 39.5%, 40.6%, 38.7%, 36.4%, and 35.4%, respectively.
- The likelihood of CRC screening did not differ between adults in the lowest vs. highest quintile of 10-year mortality risk (adjusted odds ratio, 1.05).
- More than one-quarter (27.9%) of past-year screening occurred in adults with life expectancy less than 10 years, and 50.7% of adults aged 75-84 years had life expectancy less than 10 years at the time of screening.
- Paradoxically, the prevalence of invasive screening increased with lowered life expectancy among adults aged 70-79 years.
IN PRACTICE:
“Our results suggest that health status and life expectancy may be overlooked in current CRC screening programs, and personalized screening incorporating individual life expectancy may improve the value of screening,” the authors write.
SOURCE:
The study, with first author Po-Hong Liu, MD, MPH, division of digestive and liver diseases, University of Texas Southwestern Medical Center, Dallas, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The survey data were self-reported and were not validated by medical records. The data did not include information to identify individuals who were at higher risk for CRC or to trace prior CRC screening history. It was not possible to reliably classify test indication (screening vs. surveillance vs. diagnostic).
DISCLOSURES:
The study was supported by the National Institutes of Health. One author disclosed serving as a consultant or on advisory boards for Exact Sciences, Universal Dx, Roche, and Freenome. Another disclosed consulting for Freenome.
A version of this article first appeared on Medscape.com.
TOPLINE:
Older adults with limited life expectancy are just as likely to undergo colorectal cancer (CRC) screening as those with longer life expectancy, a new study shows.
METHODOLOGY:
- Researchers used national survey data to estimate the prevalence and factors associated with CRC screening in 25,888 community-dwelling adults aged 65-84 according to their predicted 10-year mortality risk.
- They estimated 10-year mortality risk using a validated index. From the lowest to highest quintiles, mortality risk was 12%, 24%, 39%, 58%, and 79%, respectively.
- Investigators determined the proportion of screening performed in adults with life expectancy less than 10 years, defined as 10-year mortality risk ≥ 50% (that is, quintiles 4 and 5).
TAKEAWAY:
- In this cohort of older adults previously not up to date with CRC screening, the overall prevalence of past-year screening was 38.5%.
- The prevalence of past-year CRC screening decreased with advancing age but did not differ significantly by 10-year mortality risk. From lowest to highest quintile, prevalence was 39.5%, 40.6%, 38.7%, 36.4%, and 35.4%, respectively.
- The likelihood of CRC screening did not differ between adults in the lowest vs. highest quintile of 10-year mortality risk (adjusted odds ratio, 1.05).
- More than one-quarter (27.9%) of past-year screening occurred in adults with life expectancy less than 10 years, and 50.7% of adults aged 75-84 years had life expectancy less than 10 years at the time of screening.
- Paradoxically, the prevalence of invasive screening increased with lowered life expectancy among adults aged 70-79 years.
IN PRACTICE:
“Our results suggest that health status and life expectancy may be overlooked in current CRC screening programs, and personalized screening incorporating individual life expectancy may improve the value of screening,” the authors write.
SOURCE:
The study, with first author Po-Hong Liu, MD, MPH, division of digestive and liver diseases, University of Texas Southwestern Medical Center, Dallas, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The survey data were self-reported and were not validated by medical records. The data did not include information to identify individuals who were at higher risk for CRC or to trace prior CRC screening history. It was not possible to reliably classify test indication (screening vs. surveillance vs. diagnostic).
DISCLOSURES:
The study was supported by the National Institutes of Health. One author disclosed serving as a consultant or on advisory boards for Exact Sciences, Universal Dx, Roche, and Freenome. Another disclosed consulting for Freenome.
A version of this article first appeared on Medscape.com.
TOPLINE:
Older adults with limited life expectancy are just as likely to undergo colorectal cancer (CRC) screening as those with longer life expectancy, a new study shows.
METHODOLOGY:
- Researchers used national survey data to estimate the prevalence and factors associated with CRC screening in 25,888 community-dwelling adults aged 65-84 according to their predicted 10-year mortality risk.
- They estimated 10-year mortality risk using a validated index. From the lowest to highest quintiles, mortality risk was 12%, 24%, 39%, 58%, and 79%, respectively.
- Investigators determined the proportion of screening performed in adults with life expectancy less than 10 years, defined as 10-year mortality risk ≥ 50% (that is, quintiles 4 and 5).
TAKEAWAY:
- In this cohort of older adults previously not up to date with CRC screening, the overall prevalence of past-year screening was 38.5%.
- The prevalence of past-year CRC screening decreased with advancing age but did not differ significantly by 10-year mortality risk. From lowest to highest quintile, prevalence was 39.5%, 40.6%, 38.7%, 36.4%, and 35.4%, respectively.
- The likelihood of CRC screening did not differ between adults in the lowest vs. highest quintile of 10-year mortality risk (adjusted odds ratio, 1.05).
- More than one-quarter (27.9%) of past-year screening occurred in adults with life expectancy less than 10 years, and 50.7% of adults aged 75-84 years had life expectancy less than 10 years at the time of screening.
- Paradoxically, the prevalence of invasive screening increased with lowered life expectancy among adults aged 70-79 years.
IN PRACTICE:
“Our results suggest that health status and life expectancy may be overlooked in current CRC screening programs, and personalized screening incorporating individual life expectancy may improve the value of screening,” the authors write.
SOURCE:
The study, with first author Po-Hong Liu, MD, MPH, division of digestive and liver diseases, University of Texas Southwestern Medical Center, Dallas, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The survey data were self-reported and were not validated by medical records. The data did not include information to identify individuals who were at higher risk for CRC or to trace prior CRC screening history. It was not possible to reliably classify test indication (screening vs. surveillance vs. diagnostic).
DISCLOSURES:
The study was supported by the National Institutes of Health. One author disclosed serving as a consultant or on advisory boards for Exact Sciences, Universal Dx, Roche, and Freenome. Another disclosed consulting for Freenome.
A version of this article first appeared on Medscape.com.
Mixed CRC screening messaging. Confusing? Some docs think so
Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.
The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.
Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.
Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.
“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.
Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.
Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.
“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
Docs debate differing guidance
The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.
The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.
For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).
“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.
Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.
“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.
However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.
“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”
Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”
Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.
“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”
Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
Potential impact on patient outcomes, costs
Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.
Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.
Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.
“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”
Another concern is the potential effect on insurance coverage.
Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.
When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.
“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”
Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.
“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”
Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.
“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.
But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.
“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”
A version of this article first appeared on Medscape.com.
Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.
The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.
Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.
Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.
“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.
Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.
Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.
“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
Docs debate differing guidance
The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.
The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.
For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).
“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.
Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.
“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.
However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.
“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”
Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”
Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.
“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”
Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
Potential impact on patient outcomes, costs
Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.
Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.
Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.
“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”
Another concern is the potential effect on insurance coverage.
Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.
When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.
“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”
Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.
“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”
Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.
“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.
But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.
“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”
A version of this article first appeared on Medscape.com.
Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.
The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.
Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.
Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.
“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.
Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.
Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.
“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
Docs debate differing guidance
The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.
The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.
For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).
“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.
Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.
“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.
However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.
“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”
Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”
Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.
“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”
Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
Potential impact on patient outcomes, costs
Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.
Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.
Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.
“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”
Another concern is the potential effect on insurance coverage.
Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.
When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.
“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”
Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.
“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”
Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.
“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.
But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.
“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”
A version of this article first appeared on Medscape.com.
Jury out on how tea drinking influences colorectal cancer risk
TOPLINE:
A meta-analysis finds that tea drinking may reduce the risk for colorectal cancer (CRC) by 24%, but the estimate is “uncertain,” and the actual effect on CRC risk can range from a reduction of 51% to an increase of 18%, researchers say.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis of 15 studies (11 cohort, three case-control, and one randomized controlled trial) with nearly 2.7 million participants.
- The studies were conducted in Asia, North America, Europe, and Oceania between 1986 and 2015 and included black and green tea.
- Tea consumption was dichotomized as < 1 cup vs. ≥ 1 cups daily. A random effects model was used for data analysis.
TAKEAWAY:
- No statistically significant association was found between tea consumption and CRC risk (relative risk, 0.76).
- By geographic region, results of an American subgroup analysis suggested tea drinking might be protective against CRC (RR, 0.33), while data from the United Kingdom (RR, 1.45) and Italian (RR, 1.15) subgroups had opposite results.
- In subgroups by tea type, green tea was associated with a lower CRC risk (RR, 0.05).
- Sensitivity analysis revealed that the effect on CRC risk can range from a reduction of 51% (RR, 0.49) to an increase of 18% (RR, 1.18).
IN PRACTICE:
“Taken together, this meta-analysis suggests that tea consumption may not be linked to the development of CRC. These relationships still need to be confirmed by additional well-designed large prospective studies and randomized clinical trials,” the authors write.
SOURCE:
The study, with co–first authors Yu Huang and Qiang Chen, with the Third Hospital of Hebei Medical University, Shijiazhuang, China, was published online in BMC Gastroenterology.
LIMITATIONS:
There was a high level of heterogeneity in the original studies, as well as variations in the quantity and types of tea consumed and in the design and quality of the studies. Some studies did not account for potentially important variables, such as alcohol use and diet.
DISCLOSURES:
The study was supported by grants from the Hebei Provincial Natural Science Foundation and the Hebei Provincial Department of Science and Technology. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
A meta-analysis finds that tea drinking may reduce the risk for colorectal cancer (CRC) by 24%, but the estimate is “uncertain,” and the actual effect on CRC risk can range from a reduction of 51% to an increase of 18%, researchers say.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis of 15 studies (11 cohort, three case-control, and one randomized controlled trial) with nearly 2.7 million participants.
- The studies were conducted in Asia, North America, Europe, and Oceania between 1986 and 2015 and included black and green tea.
- Tea consumption was dichotomized as < 1 cup vs. ≥ 1 cups daily. A random effects model was used for data analysis.
TAKEAWAY:
- No statistically significant association was found between tea consumption and CRC risk (relative risk, 0.76).
- By geographic region, results of an American subgroup analysis suggested tea drinking might be protective against CRC (RR, 0.33), while data from the United Kingdom (RR, 1.45) and Italian (RR, 1.15) subgroups had opposite results.
- In subgroups by tea type, green tea was associated with a lower CRC risk (RR, 0.05).
- Sensitivity analysis revealed that the effect on CRC risk can range from a reduction of 51% (RR, 0.49) to an increase of 18% (RR, 1.18).
IN PRACTICE:
“Taken together, this meta-analysis suggests that tea consumption may not be linked to the development of CRC. These relationships still need to be confirmed by additional well-designed large prospective studies and randomized clinical trials,” the authors write.
SOURCE:
The study, with co–first authors Yu Huang and Qiang Chen, with the Third Hospital of Hebei Medical University, Shijiazhuang, China, was published online in BMC Gastroenterology.
LIMITATIONS:
There was a high level of heterogeneity in the original studies, as well as variations in the quantity and types of tea consumed and in the design and quality of the studies. Some studies did not account for potentially important variables, such as alcohol use and diet.
DISCLOSURES:
The study was supported by grants from the Hebei Provincial Natural Science Foundation and the Hebei Provincial Department of Science and Technology. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
A meta-analysis finds that tea drinking may reduce the risk for colorectal cancer (CRC) by 24%, but the estimate is “uncertain,” and the actual effect on CRC risk can range from a reduction of 51% to an increase of 18%, researchers say.
METHODOLOGY:
- Researchers conducted a systematic review and meta-analysis of 15 studies (11 cohort, three case-control, and one randomized controlled trial) with nearly 2.7 million participants.
- The studies were conducted in Asia, North America, Europe, and Oceania between 1986 and 2015 and included black and green tea.
- Tea consumption was dichotomized as < 1 cup vs. ≥ 1 cups daily. A random effects model was used for data analysis.
TAKEAWAY:
- No statistically significant association was found between tea consumption and CRC risk (relative risk, 0.76).
- By geographic region, results of an American subgroup analysis suggested tea drinking might be protective against CRC (RR, 0.33), while data from the United Kingdom (RR, 1.45) and Italian (RR, 1.15) subgroups had opposite results.
- In subgroups by tea type, green tea was associated with a lower CRC risk (RR, 0.05).
- Sensitivity analysis revealed that the effect on CRC risk can range from a reduction of 51% (RR, 0.49) to an increase of 18% (RR, 1.18).
IN PRACTICE:
“Taken together, this meta-analysis suggests that tea consumption may not be linked to the development of CRC. These relationships still need to be confirmed by additional well-designed large prospective studies and randomized clinical trials,” the authors write.
SOURCE:
The study, with co–first authors Yu Huang and Qiang Chen, with the Third Hospital of Hebei Medical University, Shijiazhuang, China, was published online in BMC Gastroenterology.
LIMITATIONS:
There was a high level of heterogeneity in the original studies, as well as variations in the quantity and types of tea consumed and in the design and quality of the studies. Some studies did not account for potentially important variables, such as alcohol use and diet.
DISCLOSURES:
The study was supported by grants from the Hebei Provincial Natural Science Foundation and the Hebei Provincial Department of Science and Technology. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Vegetarian diets tied to lower risk for some GI cancers
TOPLINE:
METHODOLOGY:
- Researchers did a systematic review and meta-analysis of seven original studies (six cohorts and one case-control) involving 686,691 people.
- Pooled relative risk for gastric, colorectal, and upper gastrointestinal cancers were assessed with confidence intervals in multivariate analysis accounting for potential confounders.
TAKEAWAY:
- Compared with nonvegetarian diets, vegetarian diets were inversely associated with the risk for GI tumor development (relative risk, 0.77).
- In a subgroup analysis, vegetarian diets were negatively correlated with the risk for gastric cancer (RR, 0.41) and colorectal cancer (RR, 0.85) but not with upper GI cancer (excluding stomach; RR, 0.93).
- Vegetarian diets were negatively correlated with the risk for GI cancer in men (RR, 0.57) but not women (RR, 0.89).
- Vegetarian diets were negatively correlated with the risk for GI cancer in North American (RR, 0.76) and Asian populations (RR, 0.43) but not in European populations (RR, 0.83).
IN PRACTICE:
“The results of this systematic review indicate that adherence to vegetarian diets can reduce the risk of gastrointestinal cancers, compared with non-vegetarian diets. This study provides a reference for primary prevention strategies for gastrointestinal cancers,” the authors write.
SOURCE:
The study, with first author Tongtong Bai, of Nanjing University of Chinese Medicine, was published online on in the European Journal of Gastroenterology & Hepatology.
LIMITATIONS:
The effects of vegetarian diets on GI tumorigenesis may be influenced by gender and geographical region. The heterogeneity of effects of vegetarian diets on different GI cancers could be due to the small number of studies included and could represent chance variation. The results need to be confirmed by studies of populations in other regions. There was evidence of publication bias.
DISCLOSURES:
The study had no specific funding. The authors have disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers did a systematic review and meta-analysis of seven original studies (six cohorts and one case-control) involving 686,691 people.
- Pooled relative risk for gastric, colorectal, and upper gastrointestinal cancers were assessed with confidence intervals in multivariate analysis accounting for potential confounders.
TAKEAWAY:
- Compared with nonvegetarian diets, vegetarian diets were inversely associated with the risk for GI tumor development (relative risk, 0.77).
- In a subgroup analysis, vegetarian diets were negatively correlated with the risk for gastric cancer (RR, 0.41) and colorectal cancer (RR, 0.85) but not with upper GI cancer (excluding stomach; RR, 0.93).
- Vegetarian diets were negatively correlated with the risk for GI cancer in men (RR, 0.57) but not women (RR, 0.89).
- Vegetarian diets were negatively correlated with the risk for GI cancer in North American (RR, 0.76) and Asian populations (RR, 0.43) but not in European populations (RR, 0.83).
IN PRACTICE:
“The results of this systematic review indicate that adherence to vegetarian diets can reduce the risk of gastrointestinal cancers, compared with non-vegetarian diets. This study provides a reference for primary prevention strategies for gastrointestinal cancers,” the authors write.
SOURCE:
The study, with first author Tongtong Bai, of Nanjing University of Chinese Medicine, was published online on in the European Journal of Gastroenterology & Hepatology.
LIMITATIONS:
The effects of vegetarian diets on GI tumorigenesis may be influenced by gender and geographical region. The heterogeneity of effects of vegetarian diets on different GI cancers could be due to the small number of studies included and could represent chance variation. The results need to be confirmed by studies of populations in other regions. There was evidence of publication bias.
DISCLOSURES:
The study had no specific funding. The authors have disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers did a systematic review and meta-analysis of seven original studies (six cohorts and one case-control) involving 686,691 people.
- Pooled relative risk for gastric, colorectal, and upper gastrointestinal cancers were assessed with confidence intervals in multivariate analysis accounting for potential confounders.
TAKEAWAY:
- Compared with nonvegetarian diets, vegetarian diets were inversely associated with the risk for GI tumor development (relative risk, 0.77).
- In a subgroup analysis, vegetarian diets were negatively correlated with the risk for gastric cancer (RR, 0.41) and colorectal cancer (RR, 0.85) but not with upper GI cancer (excluding stomach; RR, 0.93).
- Vegetarian diets were negatively correlated with the risk for GI cancer in men (RR, 0.57) but not women (RR, 0.89).
- Vegetarian diets were negatively correlated with the risk for GI cancer in North American (RR, 0.76) and Asian populations (RR, 0.43) but not in European populations (RR, 0.83).
IN PRACTICE:
“The results of this systematic review indicate that adherence to vegetarian diets can reduce the risk of gastrointestinal cancers, compared with non-vegetarian diets. This study provides a reference for primary prevention strategies for gastrointestinal cancers,” the authors write.
SOURCE:
The study, with first author Tongtong Bai, of Nanjing University of Chinese Medicine, was published online on in the European Journal of Gastroenterology & Hepatology.
LIMITATIONS:
The effects of vegetarian diets on GI tumorigenesis may be influenced by gender and geographical region. The heterogeneity of effects of vegetarian diets on different GI cancers could be due to the small number of studies included and could represent chance variation. The results need to be confirmed by studies of populations in other regions. There was evidence of publication bias.
DISCLOSURES:
The study had no specific funding. The authors have disclosed no conflicts of interest.
A version of this article appeared on Medscape.com.
Testing for Associations Between an Environmental Risk Score and Most Significant Colonoscopy Findings Among US Veterans in CSP #380
PURPOSE
To construct a composite score representing modifiable lifestyle and environmental risk (e-score) and test for associations with colonoscopy findings among US Veteran participants of CSP #380.
BACKGROUND
Understanding environmental and genetic risks beyond self-reported family history is a way to develop personalized colorectal cancer (CRC) screening. The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) study examined CRC risk stratified by sex and included an e-score along with genetic risk scores, where higher scores indicated higher risk. Both e-scores and genetic risk scores were significantly associated with CRC risk and models that included these were more robust than models that only included family history.
METHODS
CSP #380 is a prospective study of outcomes during colonoscopy screening (1994-97) and follow- up (1994-2009) for 3,121 asymptomatic Veterans aged 50-75. The dichotomous outcome of interest was most significant colonoscopy findings (MSCF) of i) advanced neoplasia (AN: ≥10mm adenomas or advanced histology, or invasive CRC) vs. ii) non-advanced adenomas (<10mm with tubular histology) or no neoplasia. The independent variable, e-score, was weighted according to the GECCO male sample and comprised BMI, height, diabetes, NSAID use, education, alcohol intake, smoking, exercise, and diet.
DATA ANALYSIS
Logistic regression was used to test associations between MSCF and e-scores, controlling for age, family history and number of colonoscopies.
RESULTS
Among 2,846 participants with complete data, 33.3% were aged 50-59 at baseline, 97% were male, and 83.8% were White. Those with AN (n=405, 14.2%) compared to those without AN (n=2,441, 85.8%) had higher median e-scores (29.5, range:0-99.8 vs. 29.0, range:5.2-100), suggesting a difference. The logistic regression models showed older participants (aOR: 1.04, 95% CI: 1.03-1.06) and those with more colonoscopies (aOR: 1.19, 95% CI: 1.06-1.33) had higher odds for AN. However, e-scores and family history were not significantly associated with MCSF.
IMPLICATIONS
E-scores were not significantly associated with MSCF in this preliminary study. Developing escores among a larger, diverse sample (N~381,695) of US veterans in the Million Veterans Program study will allow for stratified models in investigations of environmental and genetic risk for CRC. Outcomes from those analyses will support advances in screening guidelines with tailored programs for long-term CRC prevention.
PURPOSE
To construct a composite score representing modifiable lifestyle and environmental risk (e-score) and test for associations with colonoscopy findings among US Veteran participants of CSP #380.
BACKGROUND
Understanding environmental and genetic risks beyond self-reported family history is a way to develop personalized colorectal cancer (CRC) screening. The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) study examined CRC risk stratified by sex and included an e-score along with genetic risk scores, where higher scores indicated higher risk. Both e-scores and genetic risk scores were significantly associated with CRC risk and models that included these were more robust than models that only included family history.
METHODS
CSP #380 is a prospective study of outcomes during colonoscopy screening (1994-97) and follow- up (1994-2009) for 3,121 asymptomatic Veterans aged 50-75. The dichotomous outcome of interest was most significant colonoscopy findings (MSCF) of i) advanced neoplasia (AN: ≥10mm adenomas or advanced histology, or invasive CRC) vs. ii) non-advanced adenomas (<10mm with tubular histology) or no neoplasia. The independent variable, e-score, was weighted according to the GECCO male sample and comprised BMI, height, diabetes, NSAID use, education, alcohol intake, smoking, exercise, and diet.
DATA ANALYSIS
Logistic regression was used to test associations between MSCF and e-scores, controlling for age, family history and number of colonoscopies.
RESULTS
Among 2,846 participants with complete data, 33.3% were aged 50-59 at baseline, 97% were male, and 83.8% were White. Those with AN (n=405, 14.2%) compared to those without AN (n=2,441, 85.8%) had higher median e-scores (29.5, range:0-99.8 vs. 29.0, range:5.2-100), suggesting a difference. The logistic regression models showed older participants (aOR: 1.04, 95% CI: 1.03-1.06) and those with more colonoscopies (aOR: 1.19, 95% CI: 1.06-1.33) had higher odds for AN. However, e-scores and family history were not significantly associated with MCSF.
IMPLICATIONS
E-scores were not significantly associated with MSCF in this preliminary study. Developing escores among a larger, diverse sample (N~381,695) of US veterans in the Million Veterans Program study will allow for stratified models in investigations of environmental and genetic risk for CRC. Outcomes from those analyses will support advances in screening guidelines with tailored programs for long-term CRC prevention.
PURPOSE
To construct a composite score representing modifiable lifestyle and environmental risk (e-score) and test for associations with colonoscopy findings among US Veteran participants of CSP #380.
BACKGROUND
Understanding environmental and genetic risks beyond self-reported family history is a way to develop personalized colorectal cancer (CRC) screening. The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) study examined CRC risk stratified by sex and included an e-score along with genetic risk scores, where higher scores indicated higher risk. Both e-scores and genetic risk scores were significantly associated with CRC risk and models that included these were more robust than models that only included family history.
METHODS
CSP #380 is a prospective study of outcomes during colonoscopy screening (1994-97) and follow- up (1994-2009) for 3,121 asymptomatic Veterans aged 50-75. The dichotomous outcome of interest was most significant colonoscopy findings (MSCF) of i) advanced neoplasia (AN: ≥10mm adenomas or advanced histology, or invasive CRC) vs. ii) non-advanced adenomas (<10mm with tubular histology) or no neoplasia. The independent variable, e-score, was weighted according to the GECCO male sample and comprised BMI, height, diabetes, NSAID use, education, alcohol intake, smoking, exercise, and diet.
DATA ANALYSIS
Logistic regression was used to test associations between MSCF and e-scores, controlling for age, family history and number of colonoscopies.
RESULTS
Among 2,846 participants with complete data, 33.3% were aged 50-59 at baseline, 97% were male, and 83.8% were White. Those with AN (n=405, 14.2%) compared to those without AN (n=2,441, 85.8%) had higher median e-scores (29.5, range:0-99.8 vs. 29.0, range:5.2-100), suggesting a difference. The logistic regression models showed older participants (aOR: 1.04, 95% CI: 1.03-1.06) and those with more colonoscopies (aOR: 1.19, 95% CI: 1.06-1.33) had higher odds for AN. However, e-scores and family history were not significantly associated with MCSF.
IMPLICATIONS
E-scores were not significantly associated with MSCF in this preliminary study. Developing escores among a larger, diverse sample (N~381,695) of US veterans in the Million Veterans Program study will allow for stratified models in investigations of environmental and genetic risk for CRC. Outcomes from those analyses will support advances in screening guidelines with tailored programs for long-term CRC prevention.