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FDA OKs Next-Gen Cologuard Test for CRC Screening
Developed in collaboration with Mayo Clinic, the company noted in the news release announcing its approval that this noninvasive test “raises the performance bar.”
The company says the enhanced sensitivity will help minimize unnecessary follow-up colonoscopy procedures by reducing the odds of a false-positive screening test.
Enhanced sample stability components also will give patients more time to return their sample to the lab.
Cologuard Plus tests for three novel methylated DNA markers and fecal hemoglobin.
The BLUE-C Study
The FDA’s approval was based on the results of the BLUE-C study involving more than 20,000 adults at average risk for CRC that compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.
According to the BLUE-C results, the sensitivities of Cologuard Plus were 95% for CRC and 43% for advanced precancerous lesions, at 94% specificity with no findings on colonoscopy.
The BLUE-C results also showed that the test significantly outperformed FIT for sensitivity for CRC overall, CRC stages I-III, high-grade dysplasia, and advanced precancerous lesions.
“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early — when it is most treatable — and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, AGAF, professor of medicine at the Indiana University School of Medicine and research scientist at the Regenstrief Institute, said in the news release.
“The high colorectal cancer sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients,” said Dr. Imperiale, who served as principal investigator of the BLUE-C study.
The company plans to launch Cologuard Plus in 2025.
They anticipate that it will be covered by Medicare and included in the United States Preventive Services Task Force (USPSTF) guidelines and within quality measures.
A version of this article first appeared on Medscape.com.
Developed in collaboration with Mayo Clinic, the company noted in the news release announcing its approval that this noninvasive test “raises the performance bar.”
The company says the enhanced sensitivity will help minimize unnecessary follow-up colonoscopy procedures by reducing the odds of a false-positive screening test.
Enhanced sample stability components also will give patients more time to return their sample to the lab.
Cologuard Plus tests for three novel methylated DNA markers and fecal hemoglobin.
The BLUE-C Study
The FDA’s approval was based on the results of the BLUE-C study involving more than 20,000 adults at average risk for CRC that compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.
According to the BLUE-C results, the sensitivities of Cologuard Plus were 95% for CRC and 43% for advanced precancerous lesions, at 94% specificity with no findings on colonoscopy.
The BLUE-C results also showed that the test significantly outperformed FIT for sensitivity for CRC overall, CRC stages I-III, high-grade dysplasia, and advanced precancerous lesions.
“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early — when it is most treatable — and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, AGAF, professor of medicine at the Indiana University School of Medicine and research scientist at the Regenstrief Institute, said in the news release.
“The high colorectal cancer sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients,” said Dr. Imperiale, who served as principal investigator of the BLUE-C study.
The company plans to launch Cologuard Plus in 2025.
They anticipate that it will be covered by Medicare and included in the United States Preventive Services Task Force (USPSTF) guidelines and within quality measures.
A version of this article first appeared on Medscape.com.
Developed in collaboration with Mayo Clinic, the company noted in the news release announcing its approval that this noninvasive test “raises the performance bar.”
The company says the enhanced sensitivity will help minimize unnecessary follow-up colonoscopy procedures by reducing the odds of a false-positive screening test.
Enhanced sample stability components also will give patients more time to return their sample to the lab.
Cologuard Plus tests for three novel methylated DNA markers and fecal hemoglobin.
The BLUE-C Study
The FDA’s approval was based on the results of the BLUE-C study involving more than 20,000 adults at average risk for CRC that compared the next-generation mt-sDNA test with a fecal immunochemical test (FIT) and colonoscopy.
According to the BLUE-C results, the sensitivities of Cologuard Plus were 95% for CRC and 43% for advanced precancerous lesions, at 94% specificity with no findings on colonoscopy.
The BLUE-C results also showed that the test significantly outperformed FIT for sensitivity for CRC overall, CRC stages I-III, high-grade dysplasia, and advanced precancerous lesions.
“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early — when it is most treatable — and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, AGAF, professor of medicine at the Indiana University School of Medicine and research scientist at the Regenstrief Institute, said in the news release.
“The high colorectal cancer sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients,” said Dr. Imperiale, who served as principal investigator of the BLUE-C study.
The company plans to launch Cologuard Plus in 2025.
They anticipate that it will be covered by Medicare and included in the United States Preventive Services Task Force (USPSTF) guidelines and within quality measures.
A version of this article first appeared on Medscape.com.
Sex and Gender Influence Outcomes in Colorectal Cancer
BARCELONA, SPAIN — , according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.
“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, of University Hospital LMU Munich, Germany.
Sex and Gender: What’s New?
Speaking at the conference, Dr. Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”
Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.
Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.
From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.
However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.
Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.
“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Dr. Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.
Toward a More Targeted and Inclusive Approach
Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.
“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Dr. Heinrich said, also presenting a list of specific questionnaires to assess these components.
In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.
Gender identity influences many aspects of health, such as attitudes toward prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Dr. Heinrich said. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.
To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.
“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Dr. Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.
“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”
Dr. Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche-Janssen, Taiho, Servier, and Streamed Up.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
BARCELONA, SPAIN — , according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.
“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, of University Hospital LMU Munich, Germany.
Sex and Gender: What’s New?
Speaking at the conference, Dr. Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”
Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.
Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.
From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.
However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.
Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.
“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Dr. Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.
Toward a More Targeted and Inclusive Approach
Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.
“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Dr. Heinrich said, also presenting a list of specific questionnaires to assess these components.
In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.
Gender identity influences many aspects of health, such as attitudes toward prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Dr. Heinrich said. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.
To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.
“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Dr. Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.
“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”
Dr. Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche-Janssen, Taiho, Servier, and Streamed Up.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
BARCELONA, SPAIN — , according to experts speaking here at the European Society for Medical Oncology (ESMO) Annual Meeting 2024.
“The concepts of gender and sex are not at all new in oncology, but what is needed is a renewed focus on them and the prospective collection of data in this regard,” said Kathrin Heinrich, MD, of University Hospital LMU Munich, Germany.
Sex and Gender: What’s New?
Speaking at the conference, Dr. Heinrich cited a 2020 study published in The Lancet that stated, “Sex and gender are the foundation of precision medicine, and their differences should guide decision-making processes to promote gender equity.”
Sex differences have clear biological and pathophysiological consequences in oncology. Available data show differences between men and women in terms of gene expression, epigenetics, metabolomics, tumor microenvironment, immune system, and microbiome. These are all critical for understanding tumor biology and identifying new treatments.
Colorectal cancer provides an excellent example of how sex differences can influence treatment outcomes.
From an incidence perspective, the numbers reported by the large epidemiological GLOBOCAN study are quite similar between the two sexes, with men accounting for 56% of patients and women for 44%.
However, there are noticeable differences in tumor characteristics, with women more frequently presenting with right-sided colon tumors and BRAF mutations; both features associated with a worse prognosis.
Sex also affects body composition, influencing the percentage of metabolically active body mass, which can alter the effectiveness and distribution of a drug and the necessary dose to achieve the desired effect.
“Despite this evidence, clinical practice often overlooks differences between the sexes when planning therapies,” Dr. Heinrich said, also recalling how in many cases the side effects of treatments — from chemotherapy to immunotherapy — differ in intensity and type between men and women.
Toward a More Targeted and Inclusive Approach
Sex is a well-defined concept from a biological standpoint and, consequently, the differences between the sexes are easy to identify. Analyzing gender differences is much more complex.
“It is not enough to tick the male or female box on a questionnaire. It is necessary to consider more complex aspects to measure, such as identity, role, and gender relations,” Dr. Heinrich said, also presenting a list of specific questionnaires to assess these components.
In today’s oncology, however, such questionnaires are mainly used to analyze secondary outcomes such as quality of life, while examples from other areas of medicine, particularly cardiology, show how questionnaires on gender can predict some clinical outcomes better than those on sex alone and that studies considering sex and gender are feasible.
Gender identity influences many aspects of health, such as attitudes toward prevention, the seeking of information and medical care, and risk behaviors. “The new approach to discussing sex and gender in oncology is to consider these factors in therapeutic decisions,” Dr. Heinrich said. “I hope that within a few years this will be fully achievable, thanks to the inclusion in our studies of gender scores, ad hoc patient-reported outcomes, and information related, for example, to menopausal status or the number of pregnancies,” she added.
To harness the differences between sex and gender in favor of the patient, however, it is also necessary to change the approach to clinical studies. Currently, data on these aspects are typically collected retrospectively. However, they should be integrated prospectively from the study’s beginning.
“We look at increasingly smaller subgroups of patients, at mutations affecting 1%-2% of our patients, but we do not collect data on sex or menopausal status, which are actually extremely simple to record,” Dr. Heinrich said, calling for more inclusive studies, especially involving the LGBTQI+ community, traditionally excluded from clinical trials and many services.
“Fortunately, we live in an era in which sensitivity towards this community is continuously increasing. We must gather information on this population, which fully belongs to what we scientifically define as the ‘real-world’ approach.”
Dr. Heinrich declared honoraria, consulting and advisory roles, and travel support from several companies, including Amgen, BMS, Merck, MSD, Roche-Janssen, Taiho, Servier, and Streamed Up.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
FROM ESMO CONGRESS 2024
A CRC Blood Test Is Here. What Does it Mean for Screening?
In July, the US Food and Drug Administration (FDA) approved the first blood-based test to screen for colorectal cancer (CRC).
The FDA’s approval of Shield (Guardant Health) marks a notable achievement, as individuals at average risk now have the option to receive a simple blood test for CRC screening, starting at age 45.
“No one has an excuse anymore not to be screened,” said John Marshall, MD, director of The Ruesch Center for the Cure of Gastrointestinal Cancers and chief medical officer of the Lombardi Comprehensive Cancer Center at the Georgetown University Medical Center in Washington, DC.
The approval was based on findings from the ECLIPSE study, which reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, though only 13% sensitivity for advanced precancerous lesions.
While an exciting option, the test has its pros and cons.
The bad news, however, is that it does a poor job of detecting precancerous lesions. This could snowball if patients decide to replace a colonoscopy — which helps both detect and prevent CRC — with the blood test.
This news organization spoke to experts across three core specialties involved in the screening and treatment of CRC — primary care, gastroenterology, and oncology — to better understand both the potential value and potential pitfalls of this new option.
The interview responses have been condensed and edited for clarity.
What does this FDA approval mean for CRC screening?
David Lieberman, MD, gastroenterologist and professor emeritus at Oregon Health & Science University: Detecting circulating-free DNA associated with CRC in blood is a major scientific breakthrough. The ease of blood testing will appeal to patients and providers.
Folasade May, MD, director of the gastroenterology quality improvement program at the University of California, Los Angeles: The FDA approval means that we continue to broaden the scope of available tools to help reduce the impact of this largely preventable disease.
Dr. Marshall: Colonoscopy is still the gold standard, but we have to recognize that not everyone does it. And that not everyone wants to send their poop in the mail (with a stool-based test). Now there are no more excuses.
Alan Venook, MD, gastrointestinal medical oncologist at the University of California, San Francisco: Although it’s good to have a blood test that’s approved for CRC screening, I don’t think it moves the bar much in terms of screening. I worry about it overpromising and under-delivering. If it could find polyps or premalignant lesions, that would make a big difference; however, at 13%, that doesn’t really register, so this doesn’t really change anything.
Kenny Lin, MD, a family physician at Penn Medicine Lancaster General Health: I see this test as a good option for the 30% people of CRC screening age who are either not being screened or out of date for screening. I’m a little concerned about the people who are already getting recommended screening and may try to switch to this option.
William Golden, MD, internist and professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock, Arkansas: On a scale of 1-10, I give it a 2. It’s expensive ($900 per test without insurance). It’s also not sensitive for early cancers, which would be its main value. Frankly, there are better strategies to get patients engaged.
What do you see as the pros and cons of this test?
Dr. Lin: The pros are that it’s very convenient for patients, and it’s especially easy for physicians if they have a lab in their office and can avoid a referral where patients may never get the test. However, the data I saw were disappointing, with sensitivity and specificity falling short of the stool-based Cologuard test, which is also not invasive and less likely to miss early cancers, precancerous lesions, and polyps.
Dr. Lieberman: A major con is the detection rate of only 13% for advanced precancerous lesions, which means that this test is not likely to result in much cancer prevention. There is good evidence that if advanced precancerous lesions are detected and removed, many — if not most — CRCs can be prevented.
Dr. Marshall: Another issue is the potential for a false-positive result (which occurs for 1 in every 10 tests). With this result, you would do a scope but can’t find what’s going on. This is a big deal. It’s the first of the blood tests that will be used for cancer screening, and it could be scary for a patient to receive a positive result but not be able to figure out where it’s coming from.
Will you be recommending this test or relying on its results?
Dr. Lieberman: Patients need to understand that the blood test is inferior to every other screening test and, if selected, would result in less protection against developing CRC or dying from CRC than other screening tests. But models suggest that this test will perform better than no screening. Therefore, it is reasonable to offer the test to individuals who decline any other form of screening.
Dr. May: I will do what I’ve always done — after the FDA approval, I wait for the US Preventive Services Task Force (USPSTF) to endorse it. If it does, then I feel it’s my responsibility to tell my patients about all the options they have and stay up to date on how the tests perform, what the pros and cons are, and what reliable information will help patients make the best decision.
Dr. Venook: No, but I could potentially see us moving it into surveillance mode, where CRC survivors or patients undergoing therapy could take it, which might give us a unique second bite of the apple. The test could potentially be of value in identifying early relapse or recurrence, which might give us a heads-up or jump start on follow-up.
Are you concerned that patients won’t return for a colonoscopy after a positive result?
Dr. Golden: This concern is relevant for all tests, including fecal immunochemical test (FIT), but I’ve found that if the patient is willing to do the initial test and it comes back positive, most are willing to do the follow-up. Of course, some folks have issues with this, but now we’ll have a marker in their medical records and can re-engage them through outreach.
Dr. Lieberman: I am concerned that a patient who previously declined to have a colonoscopy may not follow up an abnormal blood test with a colonoscopy. If this occurs, it will render a blood test program ineffective for those patients. Patients should be told upfront that if the test is abnormal, a colonoscopy would be recommended.
Dr. May: This is a big concern that I have. We already have two-step screening processes with FIT, Cologuard, and CT colonography, and strong data show there is attrition. All doctors and companies will need to make it clear that if patients have an abnormal test result, they must undergo a colonoscopy. We must have activated and involved systems of patient follow-up and navigation.
Dr. Lin: I already have some concerns, given that some patients with positive FIT tests don’t get timely follow-up. I see it in my own practice where we call patients to get a colonoscopy, but they don’t take it seriously or their initial counseling wasn’t clear about the possibility of needing a follow-up colonoscopy. If people aren’t being screened for whatever reason in the first place and they get a positive result on the Shield blood test, they might be even less likely to get the necessary follow-up testing afterward.
What might this mean for insurance coverage and costs for patients?
Dr. May: This is an important question because if we don’t have equal access, we create or widen disparities. For insurers to cover Shield, it’ll need to be endorsed by major medical societies, including USPSTF. But what will happen in the beginning is that wealthy patients who can pay out of pocket will use it, while lower-income individuals won’t have access until insurers cover it.
Dr. Golden: I could do 70 (or more) FIT tests for the cost of this one blood test. A FIT test should be offered first. We’re advising the Medicaid program that physicians should be required to explain why a patient doesn’t want a FIT test, prior to covering this blood test.
Dr. Venook: It’s too early to say. Although it’s approved, we now have to look at the monetization factor. At the end of the day, we still need a colonoscopy. The science is impressive, but it doesn’t mean we need to spend $900 doing a blood test.
Dr. Lin: I could see the coverage trajectory being similar to that for Cologuard, which had little coverage when it came out 10 years ago, but eventually, Medicare and commercial coverage happened. With Shield, initially, there will be some coverage gaps, especially with commercial insurance, and I can see insurance companies having concerns, especially because the test is expensive compared with other tests and the return isn’t well known. It could also be a waste of money if people with positive tests don’t receive follow-up colonoscopies.
What else would you like to share that people may not have considered?
Dr. Marshall: These tests could pick up other genes from other cancers. My worry is that people could have another cancer detected but not find it on a colonoscopy and think the blood test must be wrong. Or they’ll do a scan, which could lead to more scans and tests.
Dr. Golden: This test has received a lot of attention and coverage that didn’t discuss other screening options, limitations, or nuances. Let’s face it — we’ll see lots of TV ads about it, but once we start dealing with the total cost of care and alternate payment models, it’s going to be hard for this test to find a niche.
Dr. Venook: This test has only been validated in a population of ages 45 years or older, which is the conventional screening population. We desperately need something that can work in younger people, where CRC rates are increasing. I’d like to see the research move in that direction.
Dr. Lin: I thought it was unique that the FDA Advisory Panel clearly stated this was better than nothing but also should be used as second-line screening. The agency took pains to say this is not a colonoscopy or even equivalent to the fecal tests in use. But they appropriately did approve it because a lot of people aren’t getting anything at all, which is the biggest problem with CRC screening.
A version of this article first appeared on Medscape.com.
In July, the US Food and Drug Administration (FDA) approved the first blood-based test to screen for colorectal cancer (CRC).
The FDA’s approval of Shield (Guardant Health) marks a notable achievement, as individuals at average risk now have the option to receive a simple blood test for CRC screening, starting at age 45.
“No one has an excuse anymore not to be screened,” said John Marshall, MD, director of The Ruesch Center for the Cure of Gastrointestinal Cancers and chief medical officer of the Lombardi Comprehensive Cancer Center at the Georgetown University Medical Center in Washington, DC.
The approval was based on findings from the ECLIPSE study, which reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, though only 13% sensitivity for advanced precancerous lesions.
While an exciting option, the test has its pros and cons.
The bad news, however, is that it does a poor job of detecting precancerous lesions. This could snowball if patients decide to replace a colonoscopy — which helps both detect and prevent CRC — with the blood test.
This news organization spoke to experts across three core specialties involved in the screening and treatment of CRC — primary care, gastroenterology, and oncology — to better understand both the potential value and potential pitfalls of this new option.
The interview responses have been condensed and edited for clarity.
What does this FDA approval mean for CRC screening?
David Lieberman, MD, gastroenterologist and professor emeritus at Oregon Health & Science University: Detecting circulating-free DNA associated with CRC in blood is a major scientific breakthrough. The ease of blood testing will appeal to patients and providers.
Folasade May, MD, director of the gastroenterology quality improvement program at the University of California, Los Angeles: The FDA approval means that we continue to broaden the scope of available tools to help reduce the impact of this largely preventable disease.
Dr. Marshall: Colonoscopy is still the gold standard, but we have to recognize that not everyone does it. And that not everyone wants to send their poop in the mail (with a stool-based test). Now there are no more excuses.
Alan Venook, MD, gastrointestinal medical oncologist at the University of California, San Francisco: Although it’s good to have a blood test that’s approved for CRC screening, I don’t think it moves the bar much in terms of screening. I worry about it overpromising and under-delivering. If it could find polyps or premalignant lesions, that would make a big difference; however, at 13%, that doesn’t really register, so this doesn’t really change anything.
Kenny Lin, MD, a family physician at Penn Medicine Lancaster General Health: I see this test as a good option for the 30% people of CRC screening age who are either not being screened or out of date for screening. I’m a little concerned about the people who are already getting recommended screening and may try to switch to this option.
William Golden, MD, internist and professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock, Arkansas: On a scale of 1-10, I give it a 2. It’s expensive ($900 per test without insurance). It’s also not sensitive for early cancers, which would be its main value. Frankly, there are better strategies to get patients engaged.
What do you see as the pros and cons of this test?
Dr. Lin: The pros are that it’s very convenient for patients, and it’s especially easy for physicians if they have a lab in their office and can avoid a referral where patients may never get the test. However, the data I saw were disappointing, with sensitivity and specificity falling short of the stool-based Cologuard test, which is also not invasive and less likely to miss early cancers, precancerous lesions, and polyps.
Dr. Lieberman: A major con is the detection rate of only 13% for advanced precancerous lesions, which means that this test is not likely to result in much cancer prevention. There is good evidence that if advanced precancerous lesions are detected and removed, many — if not most — CRCs can be prevented.
Dr. Marshall: Another issue is the potential for a false-positive result (which occurs for 1 in every 10 tests). With this result, you would do a scope but can’t find what’s going on. This is a big deal. It’s the first of the blood tests that will be used for cancer screening, and it could be scary for a patient to receive a positive result but not be able to figure out where it’s coming from.
Will you be recommending this test or relying on its results?
Dr. Lieberman: Patients need to understand that the blood test is inferior to every other screening test and, if selected, would result in less protection against developing CRC or dying from CRC than other screening tests. But models suggest that this test will perform better than no screening. Therefore, it is reasonable to offer the test to individuals who decline any other form of screening.
Dr. May: I will do what I’ve always done — after the FDA approval, I wait for the US Preventive Services Task Force (USPSTF) to endorse it. If it does, then I feel it’s my responsibility to tell my patients about all the options they have and stay up to date on how the tests perform, what the pros and cons are, and what reliable information will help patients make the best decision.
Dr. Venook: No, but I could potentially see us moving it into surveillance mode, where CRC survivors or patients undergoing therapy could take it, which might give us a unique second bite of the apple. The test could potentially be of value in identifying early relapse or recurrence, which might give us a heads-up or jump start on follow-up.
Are you concerned that patients won’t return for a colonoscopy after a positive result?
Dr. Golden: This concern is relevant for all tests, including fecal immunochemical test (FIT), but I’ve found that if the patient is willing to do the initial test and it comes back positive, most are willing to do the follow-up. Of course, some folks have issues with this, but now we’ll have a marker in their medical records and can re-engage them through outreach.
Dr. Lieberman: I am concerned that a patient who previously declined to have a colonoscopy may not follow up an abnormal blood test with a colonoscopy. If this occurs, it will render a blood test program ineffective for those patients. Patients should be told upfront that if the test is abnormal, a colonoscopy would be recommended.
Dr. May: This is a big concern that I have. We already have two-step screening processes with FIT, Cologuard, and CT colonography, and strong data show there is attrition. All doctors and companies will need to make it clear that if patients have an abnormal test result, they must undergo a colonoscopy. We must have activated and involved systems of patient follow-up and navigation.
Dr. Lin: I already have some concerns, given that some patients with positive FIT tests don’t get timely follow-up. I see it in my own practice where we call patients to get a colonoscopy, but they don’t take it seriously or their initial counseling wasn’t clear about the possibility of needing a follow-up colonoscopy. If people aren’t being screened for whatever reason in the first place and they get a positive result on the Shield blood test, they might be even less likely to get the necessary follow-up testing afterward.
What might this mean for insurance coverage and costs for patients?
Dr. May: This is an important question because if we don’t have equal access, we create or widen disparities. For insurers to cover Shield, it’ll need to be endorsed by major medical societies, including USPSTF. But what will happen in the beginning is that wealthy patients who can pay out of pocket will use it, while lower-income individuals won’t have access until insurers cover it.
Dr. Golden: I could do 70 (or more) FIT tests for the cost of this one blood test. A FIT test should be offered first. We’re advising the Medicaid program that physicians should be required to explain why a patient doesn’t want a FIT test, prior to covering this blood test.
Dr. Venook: It’s too early to say. Although it’s approved, we now have to look at the monetization factor. At the end of the day, we still need a colonoscopy. The science is impressive, but it doesn’t mean we need to spend $900 doing a blood test.
Dr. Lin: I could see the coverage trajectory being similar to that for Cologuard, which had little coverage when it came out 10 years ago, but eventually, Medicare and commercial coverage happened. With Shield, initially, there will be some coverage gaps, especially with commercial insurance, and I can see insurance companies having concerns, especially because the test is expensive compared with other tests and the return isn’t well known. It could also be a waste of money if people with positive tests don’t receive follow-up colonoscopies.
What else would you like to share that people may not have considered?
Dr. Marshall: These tests could pick up other genes from other cancers. My worry is that people could have another cancer detected but not find it on a colonoscopy and think the blood test must be wrong. Or they’ll do a scan, which could lead to more scans and tests.
Dr. Golden: This test has received a lot of attention and coverage that didn’t discuss other screening options, limitations, or nuances. Let’s face it — we’ll see lots of TV ads about it, but once we start dealing with the total cost of care and alternate payment models, it’s going to be hard for this test to find a niche.
Dr. Venook: This test has only been validated in a population of ages 45 years or older, which is the conventional screening population. We desperately need something that can work in younger people, where CRC rates are increasing. I’d like to see the research move in that direction.
Dr. Lin: I thought it was unique that the FDA Advisory Panel clearly stated this was better than nothing but also should be used as second-line screening. The agency took pains to say this is not a colonoscopy or even equivalent to the fecal tests in use. But they appropriately did approve it because a lot of people aren’t getting anything at all, which is the biggest problem with CRC screening.
A version of this article first appeared on Medscape.com.
In July, the US Food and Drug Administration (FDA) approved the first blood-based test to screen for colorectal cancer (CRC).
The FDA’s approval of Shield (Guardant Health) marks a notable achievement, as individuals at average risk now have the option to receive a simple blood test for CRC screening, starting at age 45.
“No one has an excuse anymore not to be screened,” said John Marshall, MD, director of The Ruesch Center for the Cure of Gastrointestinal Cancers and chief medical officer of the Lombardi Comprehensive Cancer Center at the Georgetown University Medical Center in Washington, DC.
The approval was based on findings from the ECLIPSE study, which reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, though only 13% sensitivity for advanced precancerous lesions.
While an exciting option, the test has its pros and cons.
The bad news, however, is that it does a poor job of detecting precancerous lesions. This could snowball if patients decide to replace a colonoscopy — which helps both detect and prevent CRC — with the blood test.
This news organization spoke to experts across three core specialties involved in the screening and treatment of CRC — primary care, gastroenterology, and oncology — to better understand both the potential value and potential pitfalls of this new option.
The interview responses have been condensed and edited for clarity.
What does this FDA approval mean for CRC screening?
David Lieberman, MD, gastroenterologist and professor emeritus at Oregon Health & Science University: Detecting circulating-free DNA associated with CRC in blood is a major scientific breakthrough. The ease of blood testing will appeal to patients and providers.
Folasade May, MD, director of the gastroenterology quality improvement program at the University of California, Los Angeles: The FDA approval means that we continue to broaden the scope of available tools to help reduce the impact of this largely preventable disease.
Dr. Marshall: Colonoscopy is still the gold standard, but we have to recognize that not everyone does it. And that not everyone wants to send their poop in the mail (with a stool-based test). Now there are no more excuses.
Alan Venook, MD, gastrointestinal medical oncologist at the University of California, San Francisco: Although it’s good to have a blood test that’s approved for CRC screening, I don’t think it moves the bar much in terms of screening. I worry about it overpromising and under-delivering. If it could find polyps or premalignant lesions, that would make a big difference; however, at 13%, that doesn’t really register, so this doesn’t really change anything.
Kenny Lin, MD, a family physician at Penn Medicine Lancaster General Health: I see this test as a good option for the 30% people of CRC screening age who are either not being screened or out of date for screening. I’m a little concerned about the people who are already getting recommended screening and may try to switch to this option.
William Golden, MD, internist and professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock, Arkansas: On a scale of 1-10, I give it a 2. It’s expensive ($900 per test without insurance). It’s also not sensitive for early cancers, which would be its main value. Frankly, there are better strategies to get patients engaged.
What do you see as the pros and cons of this test?
Dr. Lin: The pros are that it’s very convenient for patients, and it’s especially easy for physicians if they have a lab in their office and can avoid a referral where patients may never get the test. However, the data I saw were disappointing, with sensitivity and specificity falling short of the stool-based Cologuard test, which is also not invasive and less likely to miss early cancers, precancerous lesions, and polyps.
Dr. Lieberman: A major con is the detection rate of only 13% for advanced precancerous lesions, which means that this test is not likely to result in much cancer prevention. There is good evidence that if advanced precancerous lesions are detected and removed, many — if not most — CRCs can be prevented.
Dr. Marshall: Another issue is the potential for a false-positive result (which occurs for 1 in every 10 tests). With this result, you would do a scope but can’t find what’s going on. This is a big deal. It’s the first of the blood tests that will be used for cancer screening, and it could be scary for a patient to receive a positive result but not be able to figure out where it’s coming from.
Will you be recommending this test or relying on its results?
Dr. Lieberman: Patients need to understand that the blood test is inferior to every other screening test and, if selected, would result in less protection against developing CRC or dying from CRC than other screening tests. But models suggest that this test will perform better than no screening. Therefore, it is reasonable to offer the test to individuals who decline any other form of screening.
Dr. May: I will do what I’ve always done — after the FDA approval, I wait for the US Preventive Services Task Force (USPSTF) to endorse it. If it does, then I feel it’s my responsibility to tell my patients about all the options they have and stay up to date on how the tests perform, what the pros and cons are, and what reliable information will help patients make the best decision.
Dr. Venook: No, but I could potentially see us moving it into surveillance mode, where CRC survivors or patients undergoing therapy could take it, which might give us a unique second bite of the apple. The test could potentially be of value in identifying early relapse or recurrence, which might give us a heads-up or jump start on follow-up.
Are you concerned that patients won’t return for a colonoscopy after a positive result?
Dr. Golden: This concern is relevant for all tests, including fecal immunochemical test (FIT), but I’ve found that if the patient is willing to do the initial test and it comes back positive, most are willing to do the follow-up. Of course, some folks have issues with this, but now we’ll have a marker in their medical records and can re-engage them through outreach.
Dr. Lieberman: I am concerned that a patient who previously declined to have a colonoscopy may not follow up an abnormal blood test with a colonoscopy. If this occurs, it will render a blood test program ineffective for those patients. Patients should be told upfront that if the test is abnormal, a colonoscopy would be recommended.
Dr. May: This is a big concern that I have. We already have two-step screening processes with FIT, Cologuard, and CT colonography, and strong data show there is attrition. All doctors and companies will need to make it clear that if patients have an abnormal test result, they must undergo a colonoscopy. We must have activated and involved systems of patient follow-up and navigation.
Dr. Lin: I already have some concerns, given that some patients with positive FIT tests don’t get timely follow-up. I see it in my own practice where we call patients to get a colonoscopy, but they don’t take it seriously or their initial counseling wasn’t clear about the possibility of needing a follow-up colonoscopy. If people aren’t being screened for whatever reason in the first place and they get a positive result on the Shield blood test, they might be even less likely to get the necessary follow-up testing afterward.
What might this mean for insurance coverage and costs for patients?
Dr. May: This is an important question because if we don’t have equal access, we create or widen disparities. For insurers to cover Shield, it’ll need to be endorsed by major medical societies, including USPSTF. But what will happen in the beginning is that wealthy patients who can pay out of pocket will use it, while lower-income individuals won’t have access until insurers cover it.
Dr. Golden: I could do 70 (or more) FIT tests for the cost of this one blood test. A FIT test should be offered first. We’re advising the Medicaid program that physicians should be required to explain why a patient doesn’t want a FIT test, prior to covering this blood test.
Dr. Venook: It’s too early to say. Although it’s approved, we now have to look at the monetization factor. At the end of the day, we still need a colonoscopy. The science is impressive, but it doesn’t mean we need to spend $900 doing a blood test.
Dr. Lin: I could see the coverage trajectory being similar to that for Cologuard, which had little coverage when it came out 10 years ago, but eventually, Medicare and commercial coverage happened. With Shield, initially, there will be some coverage gaps, especially with commercial insurance, and I can see insurance companies having concerns, especially because the test is expensive compared with other tests and the return isn’t well known. It could also be a waste of money if people with positive tests don’t receive follow-up colonoscopies.
What else would you like to share that people may not have considered?
Dr. Marshall: These tests could pick up other genes from other cancers. My worry is that people could have another cancer detected but not find it on a colonoscopy and think the blood test must be wrong. Or they’ll do a scan, which could lead to more scans and tests.
Dr. Golden: This test has received a lot of attention and coverage that didn’t discuss other screening options, limitations, or nuances. Let’s face it — we’ll see lots of TV ads about it, but once we start dealing with the total cost of care and alternate payment models, it’s going to be hard for this test to find a niche.
Dr. Venook: This test has only been validated in a population of ages 45 years or older, which is the conventional screening population. We desperately need something that can work in younger people, where CRC rates are increasing. I’d like to see the research move in that direction.
Dr. Lin: I thought it was unique that the FDA Advisory Panel clearly stated this was better than nothing but also should be used as second-line screening. The agency took pains to say this is not a colonoscopy or even equivalent to the fecal tests in use. But they appropriately did approve it because a lot of people aren’t getting anything at all, which is the biggest problem with CRC screening.
A version of this article first appeared on Medscape.com.
Five Steps to Improved Colonoscopy Performance
According to several experts who spoke at the American Gastroenterological Association’s Postgraduate Course this spring, which was offered at Digestive Disease Week (DDW), gastroenterologists can take these five steps to improve their performance: Addressing poor bowel prep, improving polyp detection, following the best intervals for polyp surveillance, reducing the environmental impact of gastrointestinal (GI) practice, and implementing artificial intelligence (AI) tools for efficiency and quality.
Addressing Poor Prep
To improve bowel preparation rates, clinicians may consider identifying those at high risk for inadequate prep, which could include known risk factors such as age, body mass index, inpatient status, constipation, tobacco use, and hypertension. However, other variables tend to serve as bigger predictors of inadequate prep, such as the patient’s status regarding cirrhosis, Parkinson’s disease, dementia, diabetes, opioid use, gastroparesis, tricyclics, and colorectal surgery.
Although several prediction models are based on some of these factors — looking at comorbidities, antidepressant use, constipation, and prior abdominal or pelvic surgery — the data don’t indicate whether knowing about or addressing these risks actually leads to better bowel prep, said Brian Jacobson, MD, associate professor of medicine at Harvard Medical School, Boston, and director of program development for gastroenterology at Massachusetts General Hospital in Boston.
Instead, the biggest return-on-investment option is to maximize prep for all patients, he said, especially since every patient has at least some risk of poor prep, either due to the required diet changes, medication considerations, or purgative solution and timing.
To create a state-of-the-art bowel prep process, Dr. Jacobson recommended numerous tactics for all patients: Verbal and written instructions for all components of prep, patient navigation with phone or virtual messaging to guide patients through the process, a low-fiber or all-liquid diet on the day before colonoscopy, and a split-dose 2-L prep regimen. Patients should begin the second half of the split-dose regimen 4-6 hours before colonoscopy and complete it at least 2 hours before the procedure starts, and clinicians should use an irrigation pump during colonoscopy to improve visibility.
Beyond that, Dr. Jacobson noted, higher risk patients can take a split-dose 4-L prep regimen with bisacodyl, a low-fiber diet 2-3 days before colonoscopy, and a clear liquid diet the day before colonoscopy. Using simethicone as an adjunct solution can also reduce bubbles in the colon.
Future tech developments may help clinicians as well, he said, such as using AI to identify patients at high risk and modifying their prep process, creating a personalized prep on a digital platform with videos that guide patients through the process, and using a phone checklist tool to indicate when they’re ready for colonoscopy.
Improving Polyp Detection
Adenoma detection rates (ADR) can be highly variable due to different techniques, technical skills, pattern recognition, interpretation, and experience. New adjunct and AI-based tools can help improve ADR, especially if clinicians want to improve, receive training, and use best-practice techniques.
“In colonoscopy, it’s tricky because it’s not just a blood test or an x-ray. There’s really a lot of technique involved, both cognitive awareness and pattern recognition, as well as our technical skills,” said Tonya Kaltenbach, MD, professor of clinical medicine at the University of California San Francisco and director of advanced endoscopy at the San Francisco VA Health Care System in San Francisco.
For instance, multiple tools and techniques may be needed in real time to interpret a lesion, such as washing, retroflexing, and using better lighting, while paying attention to alerts and noting areas for further inspection and resection.
“This is not innate. It’s a learned skill,” she said. “It’s something we need to intentionally make efforts on and get feedback to improve.”
Improvement starts with using the right mindset for lesion detection, Dr. Kaltenbach said, by having a “reflexive recognition of deconstructed patterns of normal” — following the lines, vessels, and folds and looking for interruptions, abnormal thickness, and mucus caps. On top of that, adjunctive tools such as caps/cuffs and dye chromoendoscopy can help with proper ergonomics, irrigation, and mucosa exposure.
In the past 3 years, real-world studies using AI and computer-assisted detection have shown mixed results, with some demonstrating significant increases in ADR, while others haven’t, she said. However, being willing to try AI and other tools, such as the Endocuff cap, may help improve ADR, standardize interpretation, improve efficiency, and increase reproducibility.
“We’re always better with intentional feedback and deliberate practice,” she said. “Remember that if you improve, you’re protecting the patient from death and reducing interval cancer.”
Following Polyp Surveillance Intervals
The US Multi-Society Task Force on Colorectal Cancer’s recommendations for follow-up after colonoscopy and polypectomy provide valuable information and rationale for how to determine surveillance intervals for patients. However, clinicians still may be unsure what to recommend for some patients — or tell them to come back too soon, leading to unnecessary colonoscopy.
For instance, a 47-year-old woman who presents for her initial screening and has a single 6-mm polyp, which pathology returns as a single adenoma may be considered to be at average risk and suggested to return in 7-10 years. The guidelines seem more obvious for patients with one or two adenomas under 10 mm removed en bloc.
However, once the case details shift into gray areas and include three or four adenomas between 10 and 20 mm, or piecemeal removal, clinicians may differ on their recommendations, said Rajesh N. Keswani, MD, associate professor of medicine at the Northwestern University Feinberg School of Medicine and director of endoscopy for Northwestern Medicine in Chicago. At DDW 2024, Dr. Keswani presented several case examples, often finding various audience opinions.
In addition, he noted, recent studies have found that clinicians may estimate imprecise polyp measurements, struggle to identify sessile serrated polyposis syndrome, and often don’t follow evidence-based guidelines.
“Why do we ignore the guidelines? There’s this perception that a patient has risk factors that aren’t addressed by the guidelines, with regards to family history or a distant history of a large polyp that we don’t want to leave to the usual intervals,” he said. “We feel uncomfortable, even with our meticulous colonoscopy, telling people to come back in 10 years.”
To improve guideline adherence, Dr. Keswani suggested providing additional education, implementing an automated surveillance calculator, and using guidelines at the point of care. At Northwestern, for instance, clinicians use a hyperlink with an interpreted version of the guidelines with prior colonoscopy considerations. Overall though, practitioners should feel comfortable leaning toward longer surveillance intervals, he noted.
“More effort should be spent on getting unscreened patients in for colonoscopy than bringing back low-risk patients too early,” he said.
Reducing Environmental Effects
In recent waste audits of endoscopy rooms, providers generate 1-3 kg of waste per procedure, which would fill 117 soccer fields to a depth of 1 m, based on 18 million procedures in the United States per year. This waste comes from procedure-related equipment, administration, medications, travel of patients and staff, and infrastructure with systems such as air conditioning. Taking steps toward a green practice can reduce waste and the carbon footprint of healthcare.
“When we think about improving colonoscopy performance, the goal is to prevent colon cancer death, but when we expand that, we have to apply sustainable practices as a domain of quality,” said Heiko Pohl, MD, professor of medicine at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, and a gastroenterologist at White River Junction VA Medical Center in White River Junction, Vermont.
The GI Multisociety Strategic Plan on Environmental Sustainability suggests a 5-year initiative to improve sustainability and reduce waste across seven domains — clinical setting, education, research, society efforts, intersociety efforts, industry, and advocacy.
For instance, clinicians can take the biggest step toward sustainability by avoiding unneeded colonoscopies, Dr. Pohl said, noting that between 20% and 30% aren’t appropriate or indicated. Instead, practitioners can implement longer surveillance intervals, adhere to guidelines, and consider alternative tests, such as the fecal immunochemical test, fecal DNA, blood-based tests, and CT colonography, where relevant.
Clinicians can also rethink their approach to resection, such as using a snare first instead of forceps to reduce single-instrument use, using clip closure only when it’s truly indicated, and implementing AI-assisted optical diagnosis to help with leaving rectosigmoid polyps in place.
In terms of physical waste, practices may also reconsider how they sort bins and biohazards, looking at new ways to dispose of regulated medical waste, sharps, recyclables, and typical trash. Waste audits can help find ways to reduce paper, combine procedures, and create more efficient use of endoscopy rooms.
“We are really in a very precarious situation,” Dr. Pohl said. “It’s our generation that has a responsibility to change the course for our children’s and grandchildren’s sake.”
AI for Quality And Efficiency
Moving forward, AI tools will likely become more popular in various parts of GI practice, by assisting with documentation, spotting polyps, tracking mucosal surfaces, providing optical histopathology, and supervising performance through high-quality feedback.
“Endoscopy has reached the limits of human visual capacity, where seeing more pixels won’t necessarily improve clinical diagnosis. What’s next for elevating the care of patients really is AI,” said Jason B. Samarasena, MD, professor of medicine and program director of the interventional endoscopy training program at the University of California Irvine in Irvine, California.
As practices adopt AI-based systems, however, clinicians should be cautious about a false sense of comfort or “alarm fatigue” if bounding boxes become distracting. Instead, new tools need to be adopted as a “physician-AI hybrid,” with the endoscopist in mind, particularly if helpful for performing a better exam by watching withdrawal time or endoscope slippage.
“In real-world practice, this is being implemented without attention to endoscopist inclination and behavior,” he said. “Having a better understanding of physician attitudes could yield more optimal results.”
Notably, AI-assisted tools should be viewed akin to spell-check, which signals to the endoscopist when to pay attention and double-check an area — but primarily relies on the expert to do a high-quality exam, said Aasma Shaukat, MD, professor of medicine and director of GI outcomes research at the NYU Grossman School of Medicine, New York City.
“This should be an adjunct or an additional tool, not a replacement tool,” she added. “This doesn’t mean to stop doing astute observation.”
Future tools show promise in terms of tracking additional data related to prep quality, cecal landmarks, polyp size, mucosa exposure, histology prediction, and complete resection. These automated reports could also link to real-time dashboards, hospital or national registries, and reimbursement systems, Dr. Shaukat noted.
“At the end of the day, our interests are aligned,” she said. “Everybody cares about quality, patient satisfaction, and reimbursement, and with that goal in mind, I think some of the tools can be applied to show how we can achieve those principles together.”
Dr. Jacobson, Dr. Kaltenbach, Dr. Keswani, Dr. Pohl, Dr. Samarasena, and Dr. Shaukat reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
According to several experts who spoke at the American Gastroenterological Association’s Postgraduate Course this spring, which was offered at Digestive Disease Week (DDW), gastroenterologists can take these five steps to improve their performance: Addressing poor bowel prep, improving polyp detection, following the best intervals for polyp surveillance, reducing the environmental impact of gastrointestinal (GI) practice, and implementing artificial intelligence (AI) tools for efficiency and quality.
Addressing Poor Prep
To improve bowel preparation rates, clinicians may consider identifying those at high risk for inadequate prep, which could include known risk factors such as age, body mass index, inpatient status, constipation, tobacco use, and hypertension. However, other variables tend to serve as bigger predictors of inadequate prep, such as the patient’s status regarding cirrhosis, Parkinson’s disease, dementia, diabetes, opioid use, gastroparesis, tricyclics, and colorectal surgery.
Although several prediction models are based on some of these factors — looking at comorbidities, antidepressant use, constipation, and prior abdominal or pelvic surgery — the data don’t indicate whether knowing about or addressing these risks actually leads to better bowel prep, said Brian Jacobson, MD, associate professor of medicine at Harvard Medical School, Boston, and director of program development for gastroenterology at Massachusetts General Hospital in Boston.
Instead, the biggest return-on-investment option is to maximize prep for all patients, he said, especially since every patient has at least some risk of poor prep, either due to the required diet changes, medication considerations, or purgative solution and timing.
To create a state-of-the-art bowel prep process, Dr. Jacobson recommended numerous tactics for all patients: Verbal and written instructions for all components of prep, patient navigation with phone or virtual messaging to guide patients through the process, a low-fiber or all-liquid diet on the day before colonoscopy, and a split-dose 2-L prep regimen. Patients should begin the second half of the split-dose regimen 4-6 hours before colonoscopy and complete it at least 2 hours before the procedure starts, and clinicians should use an irrigation pump during colonoscopy to improve visibility.
Beyond that, Dr. Jacobson noted, higher risk patients can take a split-dose 4-L prep regimen with bisacodyl, a low-fiber diet 2-3 days before colonoscopy, and a clear liquid diet the day before colonoscopy. Using simethicone as an adjunct solution can also reduce bubbles in the colon.
Future tech developments may help clinicians as well, he said, such as using AI to identify patients at high risk and modifying their prep process, creating a personalized prep on a digital platform with videos that guide patients through the process, and using a phone checklist tool to indicate when they’re ready for colonoscopy.
Improving Polyp Detection
Adenoma detection rates (ADR) can be highly variable due to different techniques, technical skills, pattern recognition, interpretation, and experience. New adjunct and AI-based tools can help improve ADR, especially if clinicians want to improve, receive training, and use best-practice techniques.
“In colonoscopy, it’s tricky because it’s not just a blood test or an x-ray. There’s really a lot of technique involved, both cognitive awareness and pattern recognition, as well as our technical skills,” said Tonya Kaltenbach, MD, professor of clinical medicine at the University of California San Francisco and director of advanced endoscopy at the San Francisco VA Health Care System in San Francisco.
For instance, multiple tools and techniques may be needed in real time to interpret a lesion, such as washing, retroflexing, and using better lighting, while paying attention to alerts and noting areas for further inspection and resection.
“This is not innate. It’s a learned skill,” she said. “It’s something we need to intentionally make efforts on and get feedback to improve.”
Improvement starts with using the right mindset for lesion detection, Dr. Kaltenbach said, by having a “reflexive recognition of deconstructed patterns of normal” — following the lines, vessels, and folds and looking for interruptions, abnormal thickness, and mucus caps. On top of that, adjunctive tools such as caps/cuffs and dye chromoendoscopy can help with proper ergonomics, irrigation, and mucosa exposure.
In the past 3 years, real-world studies using AI and computer-assisted detection have shown mixed results, with some demonstrating significant increases in ADR, while others haven’t, she said. However, being willing to try AI and other tools, such as the Endocuff cap, may help improve ADR, standardize interpretation, improve efficiency, and increase reproducibility.
“We’re always better with intentional feedback and deliberate practice,” she said. “Remember that if you improve, you’re protecting the patient from death and reducing interval cancer.”
Following Polyp Surveillance Intervals
The US Multi-Society Task Force on Colorectal Cancer’s recommendations for follow-up after colonoscopy and polypectomy provide valuable information and rationale for how to determine surveillance intervals for patients. However, clinicians still may be unsure what to recommend for some patients — or tell them to come back too soon, leading to unnecessary colonoscopy.
For instance, a 47-year-old woman who presents for her initial screening and has a single 6-mm polyp, which pathology returns as a single adenoma may be considered to be at average risk and suggested to return in 7-10 years. The guidelines seem more obvious for patients with one or two adenomas under 10 mm removed en bloc.
However, once the case details shift into gray areas and include three or four adenomas between 10 and 20 mm, or piecemeal removal, clinicians may differ on their recommendations, said Rajesh N. Keswani, MD, associate professor of medicine at the Northwestern University Feinberg School of Medicine and director of endoscopy for Northwestern Medicine in Chicago. At DDW 2024, Dr. Keswani presented several case examples, often finding various audience opinions.
In addition, he noted, recent studies have found that clinicians may estimate imprecise polyp measurements, struggle to identify sessile serrated polyposis syndrome, and often don’t follow evidence-based guidelines.
“Why do we ignore the guidelines? There’s this perception that a patient has risk factors that aren’t addressed by the guidelines, with regards to family history or a distant history of a large polyp that we don’t want to leave to the usual intervals,” he said. “We feel uncomfortable, even with our meticulous colonoscopy, telling people to come back in 10 years.”
To improve guideline adherence, Dr. Keswani suggested providing additional education, implementing an automated surveillance calculator, and using guidelines at the point of care. At Northwestern, for instance, clinicians use a hyperlink with an interpreted version of the guidelines with prior colonoscopy considerations. Overall though, practitioners should feel comfortable leaning toward longer surveillance intervals, he noted.
“More effort should be spent on getting unscreened patients in for colonoscopy than bringing back low-risk patients too early,” he said.
Reducing Environmental Effects
In recent waste audits of endoscopy rooms, providers generate 1-3 kg of waste per procedure, which would fill 117 soccer fields to a depth of 1 m, based on 18 million procedures in the United States per year. This waste comes from procedure-related equipment, administration, medications, travel of patients and staff, and infrastructure with systems such as air conditioning. Taking steps toward a green practice can reduce waste and the carbon footprint of healthcare.
“When we think about improving colonoscopy performance, the goal is to prevent colon cancer death, but when we expand that, we have to apply sustainable practices as a domain of quality,” said Heiko Pohl, MD, professor of medicine at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, and a gastroenterologist at White River Junction VA Medical Center in White River Junction, Vermont.
The GI Multisociety Strategic Plan on Environmental Sustainability suggests a 5-year initiative to improve sustainability and reduce waste across seven domains — clinical setting, education, research, society efforts, intersociety efforts, industry, and advocacy.
For instance, clinicians can take the biggest step toward sustainability by avoiding unneeded colonoscopies, Dr. Pohl said, noting that between 20% and 30% aren’t appropriate or indicated. Instead, practitioners can implement longer surveillance intervals, adhere to guidelines, and consider alternative tests, such as the fecal immunochemical test, fecal DNA, blood-based tests, and CT colonography, where relevant.
Clinicians can also rethink their approach to resection, such as using a snare first instead of forceps to reduce single-instrument use, using clip closure only when it’s truly indicated, and implementing AI-assisted optical diagnosis to help with leaving rectosigmoid polyps in place.
In terms of physical waste, practices may also reconsider how they sort bins and biohazards, looking at new ways to dispose of regulated medical waste, sharps, recyclables, and typical trash. Waste audits can help find ways to reduce paper, combine procedures, and create more efficient use of endoscopy rooms.
“We are really in a very precarious situation,” Dr. Pohl said. “It’s our generation that has a responsibility to change the course for our children’s and grandchildren’s sake.”
AI for Quality And Efficiency
Moving forward, AI tools will likely become more popular in various parts of GI practice, by assisting with documentation, spotting polyps, tracking mucosal surfaces, providing optical histopathology, and supervising performance through high-quality feedback.
“Endoscopy has reached the limits of human visual capacity, where seeing more pixels won’t necessarily improve clinical diagnosis. What’s next for elevating the care of patients really is AI,” said Jason B. Samarasena, MD, professor of medicine and program director of the interventional endoscopy training program at the University of California Irvine in Irvine, California.
As practices adopt AI-based systems, however, clinicians should be cautious about a false sense of comfort or “alarm fatigue” if bounding boxes become distracting. Instead, new tools need to be adopted as a “physician-AI hybrid,” with the endoscopist in mind, particularly if helpful for performing a better exam by watching withdrawal time or endoscope slippage.
“In real-world practice, this is being implemented without attention to endoscopist inclination and behavior,” he said. “Having a better understanding of physician attitudes could yield more optimal results.”
Notably, AI-assisted tools should be viewed akin to spell-check, which signals to the endoscopist when to pay attention and double-check an area — but primarily relies on the expert to do a high-quality exam, said Aasma Shaukat, MD, professor of medicine and director of GI outcomes research at the NYU Grossman School of Medicine, New York City.
“This should be an adjunct or an additional tool, not a replacement tool,” she added. “This doesn’t mean to stop doing astute observation.”
Future tools show promise in terms of tracking additional data related to prep quality, cecal landmarks, polyp size, mucosa exposure, histology prediction, and complete resection. These automated reports could also link to real-time dashboards, hospital or national registries, and reimbursement systems, Dr. Shaukat noted.
“At the end of the day, our interests are aligned,” she said. “Everybody cares about quality, patient satisfaction, and reimbursement, and with that goal in mind, I think some of the tools can be applied to show how we can achieve those principles together.”
Dr. Jacobson, Dr. Kaltenbach, Dr. Keswani, Dr. Pohl, Dr. Samarasena, and Dr. Shaukat reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
According to several experts who spoke at the American Gastroenterological Association’s Postgraduate Course this spring, which was offered at Digestive Disease Week (DDW), gastroenterologists can take these five steps to improve their performance: Addressing poor bowel prep, improving polyp detection, following the best intervals for polyp surveillance, reducing the environmental impact of gastrointestinal (GI) practice, and implementing artificial intelligence (AI) tools for efficiency and quality.
Addressing Poor Prep
To improve bowel preparation rates, clinicians may consider identifying those at high risk for inadequate prep, which could include known risk factors such as age, body mass index, inpatient status, constipation, tobacco use, and hypertension. However, other variables tend to serve as bigger predictors of inadequate prep, such as the patient’s status regarding cirrhosis, Parkinson’s disease, dementia, diabetes, opioid use, gastroparesis, tricyclics, and colorectal surgery.
Although several prediction models are based on some of these factors — looking at comorbidities, antidepressant use, constipation, and prior abdominal or pelvic surgery — the data don’t indicate whether knowing about or addressing these risks actually leads to better bowel prep, said Brian Jacobson, MD, associate professor of medicine at Harvard Medical School, Boston, and director of program development for gastroenterology at Massachusetts General Hospital in Boston.
Instead, the biggest return-on-investment option is to maximize prep for all patients, he said, especially since every patient has at least some risk of poor prep, either due to the required diet changes, medication considerations, or purgative solution and timing.
To create a state-of-the-art bowel prep process, Dr. Jacobson recommended numerous tactics for all patients: Verbal and written instructions for all components of prep, patient navigation with phone or virtual messaging to guide patients through the process, a low-fiber or all-liquid diet on the day before colonoscopy, and a split-dose 2-L prep regimen. Patients should begin the second half of the split-dose regimen 4-6 hours before colonoscopy and complete it at least 2 hours before the procedure starts, and clinicians should use an irrigation pump during colonoscopy to improve visibility.
Beyond that, Dr. Jacobson noted, higher risk patients can take a split-dose 4-L prep regimen with bisacodyl, a low-fiber diet 2-3 days before colonoscopy, and a clear liquid diet the day before colonoscopy. Using simethicone as an adjunct solution can also reduce bubbles in the colon.
Future tech developments may help clinicians as well, he said, such as using AI to identify patients at high risk and modifying their prep process, creating a personalized prep on a digital platform with videos that guide patients through the process, and using a phone checklist tool to indicate when they’re ready for colonoscopy.
Improving Polyp Detection
Adenoma detection rates (ADR) can be highly variable due to different techniques, technical skills, pattern recognition, interpretation, and experience. New adjunct and AI-based tools can help improve ADR, especially if clinicians want to improve, receive training, and use best-practice techniques.
“In colonoscopy, it’s tricky because it’s not just a blood test or an x-ray. There’s really a lot of technique involved, both cognitive awareness and pattern recognition, as well as our technical skills,” said Tonya Kaltenbach, MD, professor of clinical medicine at the University of California San Francisco and director of advanced endoscopy at the San Francisco VA Health Care System in San Francisco.
For instance, multiple tools and techniques may be needed in real time to interpret a lesion, such as washing, retroflexing, and using better lighting, while paying attention to alerts and noting areas for further inspection and resection.
“This is not innate. It’s a learned skill,” she said. “It’s something we need to intentionally make efforts on and get feedback to improve.”
Improvement starts with using the right mindset for lesion detection, Dr. Kaltenbach said, by having a “reflexive recognition of deconstructed patterns of normal” — following the lines, vessels, and folds and looking for interruptions, abnormal thickness, and mucus caps. On top of that, adjunctive tools such as caps/cuffs and dye chromoendoscopy can help with proper ergonomics, irrigation, and mucosa exposure.
In the past 3 years, real-world studies using AI and computer-assisted detection have shown mixed results, with some demonstrating significant increases in ADR, while others haven’t, she said. However, being willing to try AI and other tools, such as the Endocuff cap, may help improve ADR, standardize interpretation, improve efficiency, and increase reproducibility.
“We’re always better with intentional feedback and deliberate practice,” she said. “Remember that if you improve, you’re protecting the patient from death and reducing interval cancer.”
Following Polyp Surveillance Intervals
The US Multi-Society Task Force on Colorectal Cancer’s recommendations for follow-up after colonoscopy and polypectomy provide valuable information and rationale for how to determine surveillance intervals for patients. However, clinicians still may be unsure what to recommend for some patients — or tell them to come back too soon, leading to unnecessary colonoscopy.
For instance, a 47-year-old woman who presents for her initial screening and has a single 6-mm polyp, which pathology returns as a single adenoma may be considered to be at average risk and suggested to return in 7-10 years. The guidelines seem more obvious for patients with one or two adenomas under 10 mm removed en bloc.
However, once the case details shift into gray areas and include three or four adenomas between 10 and 20 mm, or piecemeal removal, clinicians may differ on their recommendations, said Rajesh N. Keswani, MD, associate professor of medicine at the Northwestern University Feinberg School of Medicine and director of endoscopy for Northwestern Medicine in Chicago. At DDW 2024, Dr. Keswani presented several case examples, often finding various audience opinions.
In addition, he noted, recent studies have found that clinicians may estimate imprecise polyp measurements, struggle to identify sessile serrated polyposis syndrome, and often don’t follow evidence-based guidelines.
“Why do we ignore the guidelines? There’s this perception that a patient has risk factors that aren’t addressed by the guidelines, with regards to family history or a distant history of a large polyp that we don’t want to leave to the usual intervals,” he said. “We feel uncomfortable, even with our meticulous colonoscopy, telling people to come back in 10 years.”
To improve guideline adherence, Dr. Keswani suggested providing additional education, implementing an automated surveillance calculator, and using guidelines at the point of care. At Northwestern, for instance, clinicians use a hyperlink with an interpreted version of the guidelines with prior colonoscopy considerations. Overall though, practitioners should feel comfortable leaning toward longer surveillance intervals, he noted.
“More effort should be spent on getting unscreened patients in for colonoscopy than bringing back low-risk patients too early,” he said.
Reducing Environmental Effects
In recent waste audits of endoscopy rooms, providers generate 1-3 kg of waste per procedure, which would fill 117 soccer fields to a depth of 1 m, based on 18 million procedures in the United States per year. This waste comes from procedure-related equipment, administration, medications, travel of patients and staff, and infrastructure with systems such as air conditioning. Taking steps toward a green practice can reduce waste and the carbon footprint of healthcare.
“When we think about improving colonoscopy performance, the goal is to prevent colon cancer death, but when we expand that, we have to apply sustainable practices as a domain of quality,” said Heiko Pohl, MD, professor of medicine at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, and a gastroenterologist at White River Junction VA Medical Center in White River Junction, Vermont.
The GI Multisociety Strategic Plan on Environmental Sustainability suggests a 5-year initiative to improve sustainability and reduce waste across seven domains — clinical setting, education, research, society efforts, intersociety efforts, industry, and advocacy.
For instance, clinicians can take the biggest step toward sustainability by avoiding unneeded colonoscopies, Dr. Pohl said, noting that between 20% and 30% aren’t appropriate or indicated. Instead, practitioners can implement longer surveillance intervals, adhere to guidelines, and consider alternative tests, such as the fecal immunochemical test, fecal DNA, blood-based tests, and CT colonography, where relevant.
Clinicians can also rethink their approach to resection, such as using a snare first instead of forceps to reduce single-instrument use, using clip closure only when it’s truly indicated, and implementing AI-assisted optical diagnosis to help with leaving rectosigmoid polyps in place.
In terms of physical waste, practices may also reconsider how they sort bins and biohazards, looking at new ways to dispose of regulated medical waste, sharps, recyclables, and typical trash. Waste audits can help find ways to reduce paper, combine procedures, and create more efficient use of endoscopy rooms.
“We are really in a very precarious situation,” Dr. Pohl said. “It’s our generation that has a responsibility to change the course for our children’s and grandchildren’s sake.”
AI for Quality And Efficiency
Moving forward, AI tools will likely become more popular in various parts of GI practice, by assisting with documentation, spotting polyps, tracking mucosal surfaces, providing optical histopathology, and supervising performance through high-quality feedback.
“Endoscopy has reached the limits of human visual capacity, where seeing more pixels won’t necessarily improve clinical diagnosis. What’s next for elevating the care of patients really is AI,” said Jason B. Samarasena, MD, professor of medicine and program director of the interventional endoscopy training program at the University of California Irvine in Irvine, California.
As practices adopt AI-based systems, however, clinicians should be cautious about a false sense of comfort or “alarm fatigue” if bounding boxes become distracting. Instead, new tools need to be adopted as a “physician-AI hybrid,” with the endoscopist in mind, particularly if helpful for performing a better exam by watching withdrawal time or endoscope slippage.
“In real-world practice, this is being implemented without attention to endoscopist inclination and behavior,” he said. “Having a better understanding of physician attitudes could yield more optimal results.”
Notably, AI-assisted tools should be viewed akin to spell-check, which signals to the endoscopist when to pay attention and double-check an area — but primarily relies on the expert to do a high-quality exam, said Aasma Shaukat, MD, professor of medicine and director of GI outcomes research at the NYU Grossman School of Medicine, New York City.
“This should be an adjunct or an additional tool, not a replacement tool,” she added. “This doesn’t mean to stop doing astute observation.”
Future tools show promise in terms of tracking additional data related to prep quality, cecal landmarks, polyp size, mucosa exposure, histology prediction, and complete resection. These automated reports could also link to real-time dashboards, hospital or national registries, and reimbursement systems, Dr. Shaukat noted.
“At the end of the day, our interests are aligned,” she said. “Everybody cares about quality, patient satisfaction, and reimbursement, and with that goal in mind, I think some of the tools can be applied to show how we can achieve those principles together.”
Dr. Jacobson, Dr. Kaltenbach, Dr. Keswani, Dr. Pohl, Dr. Samarasena, and Dr. Shaukat reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Fecal Immunochemical Test Performance for CRC Screening Varies Widely
, new research suggests.
In a comparative performance analysis of five commonly used FITs for colorectal cancer (CRC) screening, researchers found statistically significant differences in positivity rates, sensitivity, and specificity, as well as important differences in rates of unusable tests.
“Our findings have practical importance for FIT-based screening programs as these differences affect the need for repeated FIT, the yield of ACN detection, and the number of diagnostic colonoscopies that would be required to follow-up on abnormal findings,” wrote the researchers, led by Barcey T. Levy, MD, PhD, with University of Iowa, Iowa City.
The study was published online in Annals of Internal Medicine.
Wide Variation Found
Despite widespread use of FITs for CRC screening, there is limited data to help guide test selection. Understanding the comparative performance of different FITs is “crucial” for a successful FIT-based screening program, the researchers wrote.
Dr. Levy and colleagues directly compared the performance of five commercially available FITs — including four qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, and QuickVue iFOB) and one quantitative test (OC-Auto FIT) — using colonoscopy as the reference standard.
Participants included a diverse group of 3761 adults (mean age, 62 years; 63% women). Each participant was given all five tests and completed them using the same stool sample. They sent the tests by first class mail to a central location, where FITs were analyzed by a trained professional on the day of receipt.
The primary outcome was test performance (sensitivity and specificity) for ACN, defined as advanced polyps or CRC.
A total of 320 participants (8.5%) were found to have ACN based on colonoscopy results, including nine with CRC (0.2%) — rates that are similar to those found in other studies.
The sensitivity for detecting ACN ranged from 10.1% (Hemoccult ICT) to 36.7% (OC-Light S FIT), and specificity varied from 85.5% (OC-Light S FIT) to 96.6% (Hemoccult ICT).
“Given the variation in FIT cutoffs reported by manufacturers, it is not surprising that tests with lower cutoffs (such as OC-Light S FIT) had higher sensitivity than tests with higher cutoffs (such as Hemoccult ICT),” Dr. Levy and colleagues wrote.
Test positivity rates varied fourfold across FITs, from 3.9% for Hemoccult ICT to 16.4% for OC-Light S FIT.
The rates of tests deemed unevaluable (due to factors such as indeterminant results or user mistakes) ranged from 0.2% for OC-Auto FIT to 2.5% for QuickVue iFOB.
The highest positive predictive value (PPV) was observed with OC-Auto FIT (28.9%) and the lowest with Hemosure iFOB (18.2%). The negative predictive value was similar across tests, ranging from 92.2% to 93.3%, indicating consistent performance in ruling out disease.
The study also identified significant differences in test sensitivity based on factors such as the location of neoplasia (higher sensitivity for distal lesions) and patient characteristics (higher sensitivity in people with higher body mass index and lower income).
Dr. Levy and colleagues said their findings have implications both in terms of clinical benefits and cost-effectiveness of CRC screening using FITs.
“Tests with lower sensitivity will miss more patients with CRC and advanced polyps, and tests with higher sensitivity and lower PPV will require more colonoscopies to detect patients with actionable findings,” they wrote.
‘Jaw-Dropping’ Results
The sensitivity results are “jaw-dropping,” Robert Smith, PhD, senior vice-president for cancer screening at the American Cancer Society, said in an interview. “A patient should have at least a 50/50 chance of having their colorectal cancer detected with a stool test at the time of testing.”
“What these numbers show is that the level that the manufacturers believe their test is performing is not reproduced,” Dr. Smith added.
This study adds to “concerns that have been raised about the inherent limitations and the performance of these tests that have been cleared for use and that are supposed to be lifesaving,” he said.
Clearance by the US Food and Drug Administration should mean that there’s essentially “no risk to using the test in terms of the test itself being harmful,” Dr. Smith said. But that’s not the case with FITs “because it’s harmful if you have cancer and your test doesn’t find it.”
By way of study limitations, Dr. Levy and colleagues said it’s important to note that they did not evaluate the “programmatic” sensitivity of repeating FIT testing every 1-2 years, as is generally recommended in screening guidelines. Therefore, the sensitivity of a single FIT may be lower than that of a repeated FIT. Also, variability in the FIT collection process by participants might have affected the results.
The study had no commercial funding. Disclosures for authors are available with the original article. Dr. Smith had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research suggests.
In a comparative performance analysis of five commonly used FITs for colorectal cancer (CRC) screening, researchers found statistically significant differences in positivity rates, sensitivity, and specificity, as well as important differences in rates of unusable tests.
“Our findings have practical importance for FIT-based screening programs as these differences affect the need for repeated FIT, the yield of ACN detection, and the number of diagnostic colonoscopies that would be required to follow-up on abnormal findings,” wrote the researchers, led by Barcey T. Levy, MD, PhD, with University of Iowa, Iowa City.
The study was published online in Annals of Internal Medicine.
Wide Variation Found
Despite widespread use of FITs for CRC screening, there is limited data to help guide test selection. Understanding the comparative performance of different FITs is “crucial” for a successful FIT-based screening program, the researchers wrote.
Dr. Levy and colleagues directly compared the performance of five commercially available FITs — including four qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, and QuickVue iFOB) and one quantitative test (OC-Auto FIT) — using colonoscopy as the reference standard.
Participants included a diverse group of 3761 adults (mean age, 62 years; 63% women). Each participant was given all five tests and completed them using the same stool sample. They sent the tests by first class mail to a central location, where FITs were analyzed by a trained professional on the day of receipt.
The primary outcome was test performance (sensitivity and specificity) for ACN, defined as advanced polyps or CRC.
A total of 320 participants (8.5%) were found to have ACN based on colonoscopy results, including nine with CRC (0.2%) — rates that are similar to those found in other studies.
The sensitivity for detecting ACN ranged from 10.1% (Hemoccult ICT) to 36.7% (OC-Light S FIT), and specificity varied from 85.5% (OC-Light S FIT) to 96.6% (Hemoccult ICT).
“Given the variation in FIT cutoffs reported by manufacturers, it is not surprising that tests with lower cutoffs (such as OC-Light S FIT) had higher sensitivity than tests with higher cutoffs (such as Hemoccult ICT),” Dr. Levy and colleagues wrote.
Test positivity rates varied fourfold across FITs, from 3.9% for Hemoccult ICT to 16.4% for OC-Light S FIT.
The rates of tests deemed unevaluable (due to factors such as indeterminant results or user mistakes) ranged from 0.2% for OC-Auto FIT to 2.5% for QuickVue iFOB.
The highest positive predictive value (PPV) was observed with OC-Auto FIT (28.9%) and the lowest with Hemosure iFOB (18.2%). The negative predictive value was similar across tests, ranging from 92.2% to 93.3%, indicating consistent performance in ruling out disease.
The study also identified significant differences in test sensitivity based on factors such as the location of neoplasia (higher sensitivity for distal lesions) and patient characteristics (higher sensitivity in people with higher body mass index and lower income).
Dr. Levy and colleagues said their findings have implications both in terms of clinical benefits and cost-effectiveness of CRC screening using FITs.
“Tests with lower sensitivity will miss more patients with CRC and advanced polyps, and tests with higher sensitivity and lower PPV will require more colonoscopies to detect patients with actionable findings,” they wrote.
‘Jaw-Dropping’ Results
The sensitivity results are “jaw-dropping,” Robert Smith, PhD, senior vice-president for cancer screening at the American Cancer Society, said in an interview. “A patient should have at least a 50/50 chance of having their colorectal cancer detected with a stool test at the time of testing.”
“What these numbers show is that the level that the manufacturers believe their test is performing is not reproduced,” Dr. Smith added.
This study adds to “concerns that have been raised about the inherent limitations and the performance of these tests that have been cleared for use and that are supposed to be lifesaving,” he said.
Clearance by the US Food and Drug Administration should mean that there’s essentially “no risk to using the test in terms of the test itself being harmful,” Dr. Smith said. But that’s not the case with FITs “because it’s harmful if you have cancer and your test doesn’t find it.”
By way of study limitations, Dr. Levy and colleagues said it’s important to note that they did not evaluate the “programmatic” sensitivity of repeating FIT testing every 1-2 years, as is generally recommended in screening guidelines. Therefore, the sensitivity of a single FIT may be lower than that of a repeated FIT. Also, variability in the FIT collection process by participants might have affected the results.
The study had no commercial funding. Disclosures for authors are available with the original article. Dr. Smith had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research suggests.
In a comparative performance analysis of five commonly used FITs for colorectal cancer (CRC) screening, researchers found statistically significant differences in positivity rates, sensitivity, and specificity, as well as important differences in rates of unusable tests.
“Our findings have practical importance for FIT-based screening programs as these differences affect the need for repeated FIT, the yield of ACN detection, and the number of diagnostic colonoscopies that would be required to follow-up on abnormal findings,” wrote the researchers, led by Barcey T. Levy, MD, PhD, with University of Iowa, Iowa City.
The study was published online in Annals of Internal Medicine.
Wide Variation Found
Despite widespread use of FITs for CRC screening, there is limited data to help guide test selection. Understanding the comparative performance of different FITs is “crucial” for a successful FIT-based screening program, the researchers wrote.
Dr. Levy and colleagues directly compared the performance of five commercially available FITs — including four qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, and QuickVue iFOB) and one quantitative test (OC-Auto FIT) — using colonoscopy as the reference standard.
Participants included a diverse group of 3761 adults (mean age, 62 years; 63% women). Each participant was given all five tests and completed them using the same stool sample. They sent the tests by first class mail to a central location, where FITs were analyzed by a trained professional on the day of receipt.
The primary outcome was test performance (sensitivity and specificity) for ACN, defined as advanced polyps or CRC.
A total of 320 participants (8.5%) were found to have ACN based on colonoscopy results, including nine with CRC (0.2%) — rates that are similar to those found in other studies.
The sensitivity for detecting ACN ranged from 10.1% (Hemoccult ICT) to 36.7% (OC-Light S FIT), and specificity varied from 85.5% (OC-Light S FIT) to 96.6% (Hemoccult ICT).
“Given the variation in FIT cutoffs reported by manufacturers, it is not surprising that tests with lower cutoffs (such as OC-Light S FIT) had higher sensitivity than tests with higher cutoffs (such as Hemoccult ICT),” Dr. Levy and colleagues wrote.
Test positivity rates varied fourfold across FITs, from 3.9% for Hemoccult ICT to 16.4% for OC-Light S FIT.
The rates of tests deemed unevaluable (due to factors such as indeterminant results or user mistakes) ranged from 0.2% for OC-Auto FIT to 2.5% for QuickVue iFOB.
The highest positive predictive value (PPV) was observed with OC-Auto FIT (28.9%) and the lowest with Hemosure iFOB (18.2%). The negative predictive value was similar across tests, ranging from 92.2% to 93.3%, indicating consistent performance in ruling out disease.
The study also identified significant differences in test sensitivity based on factors such as the location of neoplasia (higher sensitivity for distal lesions) and patient characteristics (higher sensitivity in people with higher body mass index and lower income).
Dr. Levy and colleagues said their findings have implications both in terms of clinical benefits and cost-effectiveness of CRC screening using FITs.
“Tests with lower sensitivity will miss more patients with CRC and advanced polyps, and tests with higher sensitivity and lower PPV will require more colonoscopies to detect patients with actionable findings,” they wrote.
‘Jaw-Dropping’ Results
The sensitivity results are “jaw-dropping,” Robert Smith, PhD, senior vice-president for cancer screening at the American Cancer Society, said in an interview. “A patient should have at least a 50/50 chance of having their colorectal cancer detected with a stool test at the time of testing.”
“What these numbers show is that the level that the manufacturers believe their test is performing is not reproduced,” Dr. Smith added.
This study adds to “concerns that have been raised about the inherent limitations and the performance of these tests that have been cleared for use and that are supposed to be lifesaving,” he said.
Clearance by the US Food and Drug Administration should mean that there’s essentially “no risk to using the test in terms of the test itself being harmful,” Dr. Smith said. But that’s not the case with FITs “because it’s harmful if you have cancer and your test doesn’t find it.”
By way of study limitations, Dr. Levy and colleagues said it’s important to note that they did not evaluate the “programmatic” sensitivity of repeating FIT testing every 1-2 years, as is generally recommended in screening guidelines. Therefore, the sensitivity of a single FIT may be lower than that of a repeated FIT. Also, variability in the FIT collection process by participants might have affected the results.
The study had no commercial funding. Disclosures for authors are available with the original article. Dr. Smith had no relevant disclosures.
A version of this article appeared on Medscape.com.
Five Key Measures to Ensure a Quality Colonoscopy
, a list that, for the first time, includes adequate bowel preparation and sessile serrated lesion detection rate (SSLDR).
“Endoscopy teams now have an updated set of guidelines which can be used to enhance the quality of their colonoscopies and should certainly use these current quality measures to ‘raise the bar’ on behalf of their patients,” task force member Nicholas J. Shaheen, MD, MPH, Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, said in a statement.
The task force published the recommendations online August 21 in The American Journal of Gastroenterology and in Gastrointestinal Endoscopy. It represents the third iteration of the ACG/ASGE quality indicators on colonoscopy recommendations and incorporates new evidence published since 2015.
“The last set of quality indicators from this group was 9 years ago. Since then, there has been a tremendous amount of new data published in colonoscopy quality,” Ziad F. Gellad, MD, MPH, professor of medicine, Duke University Medical Center, Durham, North Carolina, said in an interview.
“Keeping up with that data is a challenge, and so guidelines such as these are important in helping clinicians synthesize data on quality of care and implement best practices,” said Dr. Gellad, who was not involved with the task force.
Two New Priority Indicators
The task force identified 15 quality indicators, divided into preprocedure, intraprocedure, and postprocedure. It includes five “priority” indicators — two of which are new.
One is the rate of adequate bowel preparation, preferably defined as a Boston Bowel Preparation Scale score ≥ 2 in each of three colon segments or by description of the preparation as excellent, good, or adequate. It has a performance target > 90%.
“Inadequate bowel preparation substantially increases the cost of colonoscopy delivery and creates risk and inconvenience for patients, thus warranting a ranking as a priority indicator,” the task force wrote.
Dr. Gellad explained that the addition of this priority indicator is “notable because it highlights the importance of bowel prep in high-quality colonoscopy. It also shifts more of the responsibility of bowel prep from the patient to the practice.”
The second new quality indicator is the SSLDR, which was selected due to its ability to contribute to cancer prevention.
Based on available evidence, the task force recommends a current minimum threshold for the SSLDR of 6%. “This is expected to be revised upward as evidence of increasing detection occurs,” they wrote.
Dr. Gellad said the addition of SSLDR is “an important advance in these recommendations. We know that serrated adenomas are a precursor for colorectal cancer and that the detection of these subtle lesions is variable.
“Providing a benchmark encourages practices to measure the detection of serrated adenomas and intervene when rates are below benchmarks. Prior to these benchmarks, it was difficult to know where to peg our expectations,” Dr. Gellad added.
Changes to the Adenoma Detection Rate (ADR)
The ADR remains a priority indicator in the update, albeit with changes.
To keep the ADR measurement consistent with current screening guidelines, the task force now recommends that the ADR be measured starting at age 45 rather than 50 years.
“ADR plays a critical role in evaluating the performance of the colonoscopists,” task force lead Douglas K. Rex, MD, a gastroenterologist at Indiana University School of Medicine in Indianapolis, said in the statement.
“It is recommended that ADR calculations include screening, surveillance, and diagnostic colonoscopy but exclude indications of a positive noncolonoscopy screening test and therapeutic procedures for resection or treatment of known neoplasia, genetic cancer syndromes, and inflammatory bowel disease,” Dr. Rex explained.
The task force recommends a minimum ADR threshold of 35% (40% in men and 30% in women) and that colonoscopists with ADRs below 35% “undertake remedial measures to improve and to achieve acceptable performance.”
Additional Priorities
The cecal intubation rate (CIR) — the percentage of patients undergoing colonoscopy with intact colons who have full intubation of the cecum with photo documentation of cecal landmarks — remains a priority quality indicator and has a performance target ≥ 95%.
“A trained colonoscopist should achieve a high CIR with a very high level of safety,” the task force wrote. “Low CIRs have been associated with higher PCCRC [postcolonoscopy colorectal cancer] rates.”
The final priority indicator is the rate of using recommended screening and surveillance intervals, which carries a performance target ≥ 90%.
“We recommend that quality improvement efforts initially focus on high-priority indicators and then progress to other indicators once it is ascertained that endoscopists are performing above recommended thresholds, either at baseline or after corrective interventions,” the task force wrote.
“The priority indicators are absolutely important for practices to implement,” Dr. Gellad said.
“There is compelling evidence that these measures are correlated with clinically important outcomes, particularly ADR,” he added. “Many practices already capture this data, and the changes in ADR calculation make measurement less burdensome. Hopefully, this will encourage more practices to collect and report these measures.”
Dr. Rex is a consultant for Olympus, Boston Scientific, Braintree Laboratories, Norgine, GI Supply, Medtronic, and Acacia Pharmaceuticals; receives research support from Olympus, Medivators, Erbe USA, and Braintree Laboratories; and is a shareholder in Satisfai Health. Dr. Shaheen had no relevant disclosures. Dr. Gellad has consulted for Merck & Co. and Novo Nordisk and is a cofounder of Higgs Boson.
A version of this article first appeared on Medscape.com.
, a list that, for the first time, includes adequate bowel preparation and sessile serrated lesion detection rate (SSLDR).
“Endoscopy teams now have an updated set of guidelines which can be used to enhance the quality of their colonoscopies and should certainly use these current quality measures to ‘raise the bar’ on behalf of their patients,” task force member Nicholas J. Shaheen, MD, MPH, Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, said in a statement.
The task force published the recommendations online August 21 in The American Journal of Gastroenterology and in Gastrointestinal Endoscopy. It represents the third iteration of the ACG/ASGE quality indicators on colonoscopy recommendations and incorporates new evidence published since 2015.
“The last set of quality indicators from this group was 9 years ago. Since then, there has been a tremendous amount of new data published in colonoscopy quality,” Ziad F. Gellad, MD, MPH, professor of medicine, Duke University Medical Center, Durham, North Carolina, said in an interview.
“Keeping up with that data is a challenge, and so guidelines such as these are important in helping clinicians synthesize data on quality of care and implement best practices,” said Dr. Gellad, who was not involved with the task force.
Two New Priority Indicators
The task force identified 15 quality indicators, divided into preprocedure, intraprocedure, and postprocedure. It includes five “priority” indicators — two of which are new.
One is the rate of adequate bowel preparation, preferably defined as a Boston Bowel Preparation Scale score ≥ 2 in each of three colon segments or by description of the preparation as excellent, good, or adequate. It has a performance target > 90%.
“Inadequate bowel preparation substantially increases the cost of colonoscopy delivery and creates risk and inconvenience for patients, thus warranting a ranking as a priority indicator,” the task force wrote.
Dr. Gellad explained that the addition of this priority indicator is “notable because it highlights the importance of bowel prep in high-quality colonoscopy. It also shifts more of the responsibility of bowel prep from the patient to the practice.”
The second new quality indicator is the SSLDR, which was selected due to its ability to contribute to cancer prevention.
Based on available evidence, the task force recommends a current minimum threshold for the SSLDR of 6%. “This is expected to be revised upward as evidence of increasing detection occurs,” they wrote.
Dr. Gellad said the addition of SSLDR is “an important advance in these recommendations. We know that serrated adenomas are a precursor for colorectal cancer and that the detection of these subtle lesions is variable.
“Providing a benchmark encourages practices to measure the detection of serrated adenomas and intervene when rates are below benchmarks. Prior to these benchmarks, it was difficult to know where to peg our expectations,” Dr. Gellad added.
Changes to the Adenoma Detection Rate (ADR)
The ADR remains a priority indicator in the update, albeit with changes.
To keep the ADR measurement consistent with current screening guidelines, the task force now recommends that the ADR be measured starting at age 45 rather than 50 years.
“ADR plays a critical role in evaluating the performance of the colonoscopists,” task force lead Douglas K. Rex, MD, a gastroenterologist at Indiana University School of Medicine in Indianapolis, said in the statement.
“It is recommended that ADR calculations include screening, surveillance, and diagnostic colonoscopy but exclude indications of a positive noncolonoscopy screening test and therapeutic procedures for resection or treatment of known neoplasia, genetic cancer syndromes, and inflammatory bowel disease,” Dr. Rex explained.
The task force recommends a minimum ADR threshold of 35% (40% in men and 30% in women) and that colonoscopists with ADRs below 35% “undertake remedial measures to improve and to achieve acceptable performance.”
Additional Priorities
The cecal intubation rate (CIR) — the percentage of patients undergoing colonoscopy with intact colons who have full intubation of the cecum with photo documentation of cecal landmarks — remains a priority quality indicator and has a performance target ≥ 95%.
“A trained colonoscopist should achieve a high CIR with a very high level of safety,” the task force wrote. “Low CIRs have been associated with higher PCCRC [postcolonoscopy colorectal cancer] rates.”
The final priority indicator is the rate of using recommended screening and surveillance intervals, which carries a performance target ≥ 90%.
“We recommend that quality improvement efforts initially focus on high-priority indicators and then progress to other indicators once it is ascertained that endoscopists are performing above recommended thresholds, either at baseline or after corrective interventions,” the task force wrote.
“The priority indicators are absolutely important for practices to implement,” Dr. Gellad said.
“There is compelling evidence that these measures are correlated with clinically important outcomes, particularly ADR,” he added. “Many practices already capture this data, and the changes in ADR calculation make measurement less burdensome. Hopefully, this will encourage more practices to collect and report these measures.”
Dr. Rex is a consultant for Olympus, Boston Scientific, Braintree Laboratories, Norgine, GI Supply, Medtronic, and Acacia Pharmaceuticals; receives research support from Olympus, Medivators, Erbe USA, and Braintree Laboratories; and is a shareholder in Satisfai Health. Dr. Shaheen had no relevant disclosures. Dr. Gellad has consulted for Merck & Co. and Novo Nordisk and is a cofounder of Higgs Boson.
A version of this article first appeared on Medscape.com.
, a list that, for the first time, includes adequate bowel preparation and sessile serrated lesion detection rate (SSLDR).
“Endoscopy teams now have an updated set of guidelines which can be used to enhance the quality of their colonoscopies and should certainly use these current quality measures to ‘raise the bar’ on behalf of their patients,” task force member Nicholas J. Shaheen, MD, MPH, Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill, said in a statement.
The task force published the recommendations online August 21 in The American Journal of Gastroenterology and in Gastrointestinal Endoscopy. It represents the third iteration of the ACG/ASGE quality indicators on colonoscopy recommendations and incorporates new evidence published since 2015.
“The last set of quality indicators from this group was 9 years ago. Since then, there has been a tremendous amount of new data published in colonoscopy quality,” Ziad F. Gellad, MD, MPH, professor of medicine, Duke University Medical Center, Durham, North Carolina, said in an interview.
“Keeping up with that data is a challenge, and so guidelines such as these are important in helping clinicians synthesize data on quality of care and implement best practices,” said Dr. Gellad, who was not involved with the task force.
Two New Priority Indicators
The task force identified 15 quality indicators, divided into preprocedure, intraprocedure, and postprocedure. It includes five “priority” indicators — two of which are new.
One is the rate of adequate bowel preparation, preferably defined as a Boston Bowel Preparation Scale score ≥ 2 in each of three colon segments or by description of the preparation as excellent, good, or adequate. It has a performance target > 90%.
“Inadequate bowel preparation substantially increases the cost of colonoscopy delivery and creates risk and inconvenience for patients, thus warranting a ranking as a priority indicator,” the task force wrote.
Dr. Gellad explained that the addition of this priority indicator is “notable because it highlights the importance of bowel prep in high-quality colonoscopy. It also shifts more of the responsibility of bowel prep from the patient to the practice.”
The second new quality indicator is the SSLDR, which was selected due to its ability to contribute to cancer prevention.
Based on available evidence, the task force recommends a current minimum threshold for the SSLDR of 6%. “This is expected to be revised upward as evidence of increasing detection occurs,” they wrote.
Dr. Gellad said the addition of SSLDR is “an important advance in these recommendations. We know that serrated adenomas are a precursor for colorectal cancer and that the detection of these subtle lesions is variable.
“Providing a benchmark encourages practices to measure the detection of serrated adenomas and intervene when rates are below benchmarks. Prior to these benchmarks, it was difficult to know where to peg our expectations,” Dr. Gellad added.
Changes to the Adenoma Detection Rate (ADR)
The ADR remains a priority indicator in the update, albeit with changes.
To keep the ADR measurement consistent with current screening guidelines, the task force now recommends that the ADR be measured starting at age 45 rather than 50 years.
“ADR plays a critical role in evaluating the performance of the colonoscopists,” task force lead Douglas K. Rex, MD, a gastroenterologist at Indiana University School of Medicine in Indianapolis, said in the statement.
“It is recommended that ADR calculations include screening, surveillance, and diagnostic colonoscopy but exclude indications of a positive noncolonoscopy screening test and therapeutic procedures for resection or treatment of known neoplasia, genetic cancer syndromes, and inflammatory bowel disease,” Dr. Rex explained.
The task force recommends a minimum ADR threshold of 35% (40% in men and 30% in women) and that colonoscopists with ADRs below 35% “undertake remedial measures to improve and to achieve acceptable performance.”
Additional Priorities
The cecal intubation rate (CIR) — the percentage of patients undergoing colonoscopy with intact colons who have full intubation of the cecum with photo documentation of cecal landmarks — remains a priority quality indicator and has a performance target ≥ 95%.
“A trained colonoscopist should achieve a high CIR with a very high level of safety,” the task force wrote. “Low CIRs have been associated with higher PCCRC [postcolonoscopy colorectal cancer] rates.”
The final priority indicator is the rate of using recommended screening and surveillance intervals, which carries a performance target ≥ 90%.
“We recommend that quality improvement efforts initially focus on high-priority indicators and then progress to other indicators once it is ascertained that endoscopists are performing above recommended thresholds, either at baseline or after corrective interventions,” the task force wrote.
“The priority indicators are absolutely important for practices to implement,” Dr. Gellad said.
“There is compelling evidence that these measures are correlated with clinically important outcomes, particularly ADR,” he added. “Many practices already capture this data, and the changes in ADR calculation make measurement less burdensome. Hopefully, this will encourage more practices to collect and report these measures.”
Dr. Rex is a consultant for Olympus, Boston Scientific, Braintree Laboratories, Norgine, GI Supply, Medtronic, and Acacia Pharmaceuticals; receives research support from Olympus, Medivators, Erbe USA, and Braintree Laboratories; and is a shareholder in Satisfai Health. Dr. Shaheen had no relevant disclosures. Dr. Gellad has consulted for Merck & Co. and Novo Nordisk and is a cofounder of Higgs Boson.
A version of this article first appeared on Medscape.com.
Is Red Meat Healthy? Multiverse Analysis Has Lessons Beyond Meat
Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise.
Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.
My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.
But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.
A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
Multiple Ways to Slice the Data
Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality.
Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies.
You might wonder how there could be thousands of ways to analyze a dataset. I surely did.
The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.
Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.
For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association.
Is Red Meat Good or Bad?
Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality.
Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review.
They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals.
Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology.
Specification Curve Analyses Results
Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.
- The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
- The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
- Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
- As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
- Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
- Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.
Paradigm Changing
As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have.
Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method.
Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result.
Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null.
What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible.
The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data.
I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices?
Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.
Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise.
Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.
My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.
But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.
A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
Multiple Ways to Slice the Data
Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality.
Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies.
You might wonder how there could be thousands of ways to analyze a dataset. I surely did.
The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.
Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.
For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association.
Is Red Meat Good or Bad?
Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality.
Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review.
They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals.
Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology.
Specification Curve Analyses Results
Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.
- The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
- The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
- Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
- As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
- Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
- Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.
Paradigm Changing
As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have.
Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method.
Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result.
Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null.
What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible.
The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data.
I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices?
Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.
Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise.
Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.
My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.
But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.
A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
Multiple Ways to Slice the Data
Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality.
Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies.
You might wonder how there could be thousands of ways to analyze a dataset. I surely did.
The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.
Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.
For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association.
Is Red Meat Good or Bad?
Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality.
Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review.
They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals.
Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology.
Specification Curve Analyses Results
Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.
- The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
- The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
- Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
- As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
- Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
- Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.
Paradigm Changing
As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have.
Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method.
Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result.
Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null.
What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible.
The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data.
I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices?
Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.
Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Blood Test Shows Promise for Improving CRC Screening
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
New CRC Risk Prediction Model Outperforms Polyp-Based Model
TOPLINE:
A comprehensive model considering patient age, diabetes, colonoscopy indications, and polyp findings can predict colorectal cancer (CRC) risk more accurately than the solely polyp-based model in patients with a first diagnosis of adenoma on colonoscopy.
METHODOLOGY:
- Because colonoscopy surveillance guidelines relying solely on previous polyp findings to assess CRC risk are imprecise, researchers developed and tested a comprehensive risk prediction model from a list of CRC-related predictors that included patient characteristics and clinical factors in addition to polyp findings.
- The comprehensive model included baseline colonoscopy indication, age group, diabetes diagnosis, and polyp findings (adenoma with advanced histology, polyp size ≥ 10 mm, and sessile serrated or traditional serrated adenoma).
- They randomly assigned 95,001 patients (mean age, 61.9 years; 45.5% women) who underwent colonoscopy with polypectomy to remove a conventional adenoma into two cohorts: Model development (66,500) and internal validation (28,501).
- In both cohorts, researchers compared the performance of the polyp findings-only method against the comprehensive model in predicting CRC, defined as an adenocarcinoma of the colon or rectum diagnosed a year after the baseline colonoscopy.
TAKEAWAY:
- During the follow-up period starting 1 year after colonoscopy, 495 patients were diagnosed with CRC; 354 were in the development cohort and 141 were in the validation cohort.
- The comprehensive model demonstrated better predictive performance than the traditional polyp-based model in the development cohort (area under the curve [AUC], 0.71 vs 0.61) and in the validation cohort (AUC, 0.7 vs 0.62).
- The difference in the Akaike Information Criterion values between the comprehensive and polyp models was 45.7, much above the threshold of 10, strongly indicating the superior performance of the comprehensive model.
IN PRACTICE:
“Improving the ability to accurately predict the patients at highest risk for CRC after polypectomy is critically important, given the considerable costs and resources associated with treating CRC and the better prognosis associated with early cancer detection. The current findings provide proof of concept that inclusion of CRC risk factors beyond prior polyp findings has the potential to improve post-colonoscopy risk stratification,” the authors wrote.
SOURCE:
The study, led by Jeffrey K. Lee, MD, MPH, Division of Research, Kaiser Permanente Northern California, Oakland, California, was published online in The American Journal of Gastroenterology.
LIMITATIONS:
External validation of the model’s performance is needed in different practice settings. The generalizability of the findings is limited because the study population did not include individuals without a prior adenoma or those with an isolated serrated polyp. Moreover, the examination of polyp size > 20 mm as a potential predictor of CRC was precluded due to incomplete data.
DISCLOSURES:
The study was conducted within the National Cancer Institute–funded Population-Based Research to Optimize the Screening Process II consortium and funded by a career development grant from the National Cancer Institute to Lee. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A comprehensive model considering patient age, diabetes, colonoscopy indications, and polyp findings can predict colorectal cancer (CRC) risk more accurately than the solely polyp-based model in patients with a first diagnosis of adenoma on colonoscopy.
METHODOLOGY:
- Because colonoscopy surveillance guidelines relying solely on previous polyp findings to assess CRC risk are imprecise, researchers developed and tested a comprehensive risk prediction model from a list of CRC-related predictors that included patient characteristics and clinical factors in addition to polyp findings.
- The comprehensive model included baseline colonoscopy indication, age group, diabetes diagnosis, and polyp findings (adenoma with advanced histology, polyp size ≥ 10 mm, and sessile serrated or traditional serrated adenoma).
- They randomly assigned 95,001 patients (mean age, 61.9 years; 45.5% women) who underwent colonoscopy with polypectomy to remove a conventional adenoma into two cohorts: Model development (66,500) and internal validation (28,501).
- In both cohorts, researchers compared the performance of the polyp findings-only method against the comprehensive model in predicting CRC, defined as an adenocarcinoma of the colon or rectum diagnosed a year after the baseline colonoscopy.
TAKEAWAY:
- During the follow-up period starting 1 year after colonoscopy, 495 patients were diagnosed with CRC; 354 were in the development cohort and 141 were in the validation cohort.
- The comprehensive model demonstrated better predictive performance than the traditional polyp-based model in the development cohort (area under the curve [AUC], 0.71 vs 0.61) and in the validation cohort (AUC, 0.7 vs 0.62).
- The difference in the Akaike Information Criterion values between the comprehensive and polyp models was 45.7, much above the threshold of 10, strongly indicating the superior performance of the comprehensive model.
IN PRACTICE:
“Improving the ability to accurately predict the patients at highest risk for CRC after polypectomy is critically important, given the considerable costs and resources associated with treating CRC and the better prognosis associated with early cancer detection. The current findings provide proof of concept that inclusion of CRC risk factors beyond prior polyp findings has the potential to improve post-colonoscopy risk stratification,” the authors wrote.
SOURCE:
The study, led by Jeffrey K. Lee, MD, MPH, Division of Research, Kaiser Permanente Northern California, Oakland, California, was published online in The American Journal of Gastroenterology.
LIMITATIONS:
External validation of the model’s performance is needed in different practice settings. The generalizability of the findings is limited because the study population did not include individuals without a prior adenoma or those with an isolated serrated polyp. Moreover, the examination of polyp size > 20 mm as a potential predictor of CRC was precluded due to incomplete data.
DISCLOSURES:
The study was conducted within the National Cancer Institute–funded Population-Based Research to Optimize the Screening Process II consortium and funded by a career development grant from the National Cancer Institute to Lee. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A comprehensive model considering patient age, diabetes, colonoscopy indications, and polyp findings can predict colorectal cancer (CRC) risk more accurately than the solely polyp-based model in patients with a first diagnosis of adenoma on colonoscopy.
METHODOLOGY:
- Because colonoscopy surveillance guidelines relying solely on previous polyp findings to assess CRC risk are imprecise, researchers developed and tested a comprehensive risk prediction model from a list of CRC-related predictors that included patient characteristics and clinical factors in addition to polyp findings.
- The comprehensive model included baseline colonoscopy indication, age group, diabetes diagnosis, and polyp findings (adenoma with advanced histology, polyp size ≥ 10 mm, and sessile serrated or traditional serrated adenoma).
- They randomly assigned 95,001 patients (mean age, 61.9 years; 45.5% women) who underwent colonoscopy with polypectomy to remove a conventional adenoma into two cohorts: Model development (66,500) and internal validation (28,501).
- In both cohorts, researchers compared the performance of the polyp findings-only method against the comprehensive model in predicting CRC, defined as an adenocarcinoma of the colon or rectum diagnosed a year after the baseline colonoscopy.
TAKEAWAY:
- During the follow-up period starting 1 year after colonoscopy, 495 patients were diagnosed with CRC; 354 were in the development cohort and 141 were in the validation cohort.
- The comprehensive model demonstrated better predictive performance than the traditional polyp-based model in the development cohort (area under the curve [AUC], 0.71 vs 0.61) and in the validation cohort (AUC, 0.7 vs 0.62).
- The difference in the Akaike Information Criterion values between the comprehensive and polyp models was 45.7, much above the threshold of 10, strongly indicating the superior performance of the comprehensive model.
IN PRACTICE:
“Improving the ability to accurately predict the patients at highest risk for CRC after polypectomy is critically important, given the considerable costs and resources associated with treating CRC and the better prognosis associated with early cancer detection. The current findings provide proof of concept that inclusion of CRC risk factors beyond prior polyp findings has the potential to improve post-colonoscopy risk stratification,” the authors wrote.
SOURCE:
The study, led by Jeffrey K. Lee, MD, MPH, Division of Research, Kaiser Permanente Northern California, Oakland, California, was published online in The American Journal of Gastroenterology.
LIMITATIONS:
External validation of the model’s performance is needed in different practice settings. The generalizability of the findings is limited because the study population did not include individuals without a prior adenoma or those with an isolated serrated polyp. Moreover, the examination of polyp size > 20 mm as a potential predictor of CRC was precluded due to incomplete data.
DISCLOSURES:
The study was conducted within the National Cancer Institute–funded Population-Based Research to Optimize the Screening Process II consortium and funded by a career development grant from the National Cancer Institute to Lee. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Does Bariatric Surgery Increase or Decrease Cancer Risk? It Depends.
Bariatric surgery appears to decrease the risk for some cancers, but it may increase the risk for others, particularly colorectal cancer (CRC), according to a synthesis of current evidence.
“There has been a recent burst of studies examining the association between bariatric surgery and the longitudinal risks of developing cancer,” corresponding author Zhi Ven Fong, MD, MPH, DrPH, surgical oncologist, Mayo Clinic Arizona, Phoenix, said in an interview. “However, there has not been a rigorous and critical analysis of the data published to date.”
In evaluating research showing an association between bariatric surgery and longitudinal cancer risk, the investigators found that the quality of the studies and their findings are “heterogeneous and might be susceptible to bias,” Dr. Fong said.
Bariatric surgery appears to have the strongest and most consistent association with the reduction of breast, ovarian, and endometrial cancer risk, first author Pei-Wen Lim, MD, MS, bariatric surgeon at Mayo Clinic Arizona, Phoenix, told this news organization. “However, there have been concerning signals from preclinical and epidemiological studies that bariatric surgery may be associated with a higher risk of developing colorectal cancers,” she added.
The authors cautioned against certain changes in clinical management.
“First, cancer surveillance frequency should not be altered after bariatric surgery because of any assumed reduction in longitudinal cancer risk, and surveillance strategy should mirror that of an average-risk individual,” they wrote. “Secondly, the indications for bariatric surgery should not be expanded for the purpose of cancer-risk mitigation.”
The review was published online in JAMA Surgery.
Protection Against Hormone-Related Cancers
The authors pointed to several studies that appear to support the association between bariatric surgery and decreased risk for hormone-related cancers.
Among them is an observational study of 6781 patients in Canada that showed a significant reduction in breast cancer risk at a median follow-up of 5 years in those who had bariatric surgery vs those who did not (P = .01).
The largest study to date on risk for hormone-related cancer after bariatric surgery was conducted using New York State data for 302,883 women.
It showed a lower rate of breast, endometrial, and ovarian cancers after bariatric surgery (hazard ratio [HR], 0.78; P < .001), with Roux-en-Y gastric bypass conferring the greatest benefit compared with laparoscopic sleeve gastrectomy (HR, 0.66; P = .006) and laparoscopic adjustable gastric banding (HR, 0.83; P = .006).
Beyond the shared mechanisms explaining obesity and cancer risk, a proposed explanation for the strong, consistent association between bariatric surgery and hormone-sensitive cancers is the role obesity-related changes in estrogen stimulation play in development of such cancers, the authors noted.
Association With GI Cancers
The association between bariatric surgery and development of esophageal, gastric, liver, and pancreas cancers is less clear. The data are heterogeneous, with studies showing either no association or decreased longitudinal incidence, the authors reported.
The data are also mixed when it comes to CRC. Epidemiological studies have demonstrated decreased longitudinal incidence of colon and rectal cancer after bariatric surgery; however, two studies have suggested an increased CRC risk after bariatric surgery, the authors noted.
A 15-year study from England that matched 8794 patients with obesity who underwent bariatric surgery with 8794 patients with obesity who did not have the surgery showed that gastric bypass (but not gastric banding or sleeve gastrectomy) was associated with a greater than twofold increased risk of developing colon and rectal cancer (odds ratio, 2.63).
These findings were corroborated in a Swedish cohort study with more than 10 years of follow-up data.
One potential explanation for the heterogeneous findings is that “present studies do not discriminate the sub-types of colon and rectal cancer, with bariatric surgery possibly increasing the incidence of colitis-associated cancers but not hereditary cancers,” the authors wrote.
“The mechanism by which gastric bypass may increase the risk of colorectal cancer is through changes in the gut’s microbiome. These changes in gut flora may triumph the protective effect of weight loss on the development of colorectal cancers,” Dr. Fong said.
Prospective studies are necessary to better delineate CRC risk after bariatric surgery, the authors wrote.
Benefits Outweigh Risk
“Ultimately, it has been proven that bariatric surgery saves lives by improving the metabolic profile of patients with obesity through reduction in cardiovascular risk factors such as hypertension, diabetes, and nonalcoholic fatty liver disease,” Dr. Lim said.
“If patients qualify for bariatric surgery on the basis of their BMI or comorbidities, they should pursue it for its metabolic benefits, but perhaps consider timely or closer-interval screening colonoscopies to monitor for potential colorectal cancer development,” Dr. Lim added.
When asked to comment on the review, Marina Kurian, MD, president, American Society for Metabolic and Bariatric Surgery, also pointed to the advantages of bariatric surgery in reducing major adverse cardiovascular events and improving hypertension, hyperlipidemia, and diabetes.
Bariatric surgery reduces many types of cancers, although the data specific to CRC risk with bariatric surgery are mixed, she added.
“The jury is still out,” said Dr. Kurian, clinical professor of surgery at NYU Langone Health in New York, who was not involved in the review. “There are papers and meta-analyses that show benefit even in colorectal cancer, but then there are a couple of papers out there that suggest a risk that seems to be specific to men.
“It could just be a numbers game, where we may not have enough data. We need more granular data that will help address these nuances and really determine what is the actual risk,” Dr. Kurian said. “But overall, for cancer, bariatric surgery is a win.”
This research had no specific funding. Dr. Fong and Dr. Lim had no relevant disclosures. Dr. Kurian disclosed relationships with Allergan, Allurion, CineMed, CSATS, Ezisurg Medical, Hernon, Johnson & Johnson, Medtronic, Novo, Stryker, and Vivus.
A version of this article appeared on Medscape.com.
Bariatric surgery appears to decrease the risk for some cancers, but it may increase the risk for others, particularly colorectal cancer (CRC), according to a synthesis of current evidence.
“There has been a recent burst of studies examining the association between bariatric surgery and the longitudinal risks of developing cancer,” corresponding author Zhi Ven Fong, MD, MPH, DrPH, surgical oncologist, Mayo Clinic Arizona, Phoenix, said in an interview. “However, there has not been a rigorous and critical analysis of the data published to date.”
In evaluating research showing an association between bariatric surgery and longitudinal cancer risk, the investigators found that the quality of the studies and their findings are “heterogeneous and might be susceptible to bias,” Dr. Fong said.
Bariatric surgery appears to have the strongest and most consistent association with the reduction of breast, ovarian, and endometrial cancer risk, first author Pei-Wen Lim, MD, MS, bariatric surgeon at Mayo Clinic Arizona, Phoenix, told this news organization. “However, there have been concerning signals from preclinical and epidemiological studies that bariatric surgery may be associated with a higher risk of developing colorectal cancers,” she added.
The authors cautioned against certain changes in clinical management.
“First, cancer surveillance frequency should not be altered after bariatric surgery because of any assumed reduction in longitudinal cancer risk, and surveillance strategy should mirror that of an average-risk individual,” they wrote. “Secondly, the indications for bariatric surgery should not be expanded for the purpose of cancer-risk mitigation.”
The review was published online in JAMA Surgery.
Protection Against Hormone-Related Cancers
The authors pointed to several studies that appear to support the association between bariatric surgery and decreased risk for hormone-related cancers.
Among them is an observational study of 6781 patients in Canada that showed a significant reduction in breast cancer risk at a median follow-up of 5 years in those who had bariatric surgery vs those who did not (P = .01).
The largest study to date on risk for hormone-related cancer after bariatric surgery was conducted using New York State data for 302,883 women.
It showed a lower rate of breast, endometrial, and ovarian cancers after bariatric surgery (hazard ratio [HR], 0.78; P < .001), with Roux-en-Y gastric bypass conferring the greatest benefit compared with laparoscopic sleeve gastrectomy (HR, 0.66; P = .006) and laparoscopic adjustable gastric banding (HR, 0.83; P = .006).
Beyond the shared mechanisms explaining obesity and cancer risk, a proposed explanation for the strong, consistent association between bariatric surgery and hormone-sensitive cancers is the role obesity-related changes in estrogen stimulation play in development of such cancers, the authors noted.
Association With GI Cancers
The association between bariatric surgery and development of esophageal, gastric, liver, and pancreas cancers is less clear. The data are heterogeneous, with studies showing either no association or decreased longitudinal incidence, the authors reported.
The data are also mixed when it comes to CRC. Epidemiological studies have demonstrated decreased longitudinal incidence of colon and rectal cancer after bariatric surgery; however, two studies have suggested an increased CRC risk after bariatric surgery, the authors noted.
A 15-year study from England that matched 8794 patients with obesity who underwent bariatric surgery with 8794 patients with obesity who did not have the surgery showed that gastric bypass (but not gastric banding or sleeve gastrectomy) was associated with a greater than twofold increased risk of developing colon and rectal cancer (odds ratio, 2.63).
These findings were corroborated in a Swedish cohort study with more than 10 years of follow-up data.
One potential explanation for the heterogeneous findings is that “present studies do not discriminate the sub-types of colon and rectal cancer, with bariatric surgery possibly increasing the incidence of colitis-associated cancers but not hereditary cancers,” the authors wrote.
“The mechanism by which gastric bypass may increase the risk of colorectal cancer is through changes in the gut’s microbiome. These changes in gut flora may triumph the protective effect of weight loss on the development of colorectal cancers,” Dr. Fong said.
Prospective studies are necessary to better delineate CRC risk after bariatric surgery, the authors wrote.
Benefits Outweigh Risk
“Ultimately, it has been proven that bariatric surgery saves lives by improving the metabolic profile of patients with obesity through reduction in cardiovascular risk factors such as hypertension, diabetes, and nonalcoholic fatty liver disease,” Dr. Lim said.
“If patients qualify for bariatric surgery on the basis of their BMI or comorbidities, they should pursue it for its metabolic benefits, but perhaps consider timely or closer-interval screening colonoscopies to monitor for potential colorectal cancer development,” Dr. Lim added.
When asked to comment on the review, Marina Kurian, MD, president, American Society for Metabolic and Bariatric Surgery, also pointed to the advantages of bariatric surgery in reducing major adverse cardiovascular events and improving hypertension, hyperlipidemia, and diabetes.
Bariatric surgery reduces many types of cancers, although the data specific to CRC risk with bariatric surgery are mixed, she added.
“The jury is still out,” said Dr. Kurian, clinical professor of surgery at NYU Langone Health in New York, who was not involved in the review. “There are papers and meta-analyses that show benefit even in colorectal cancer, but then there are a couple of papers out there that suggest a risk that seems to be specific to men.
“It could just be a numbers game, where we may not have enough data. We need more granular data that will help address these nuances and really determine what is the actual risk,” Dr. Kurian said. “But overall, for cancer, bariatric surgery is a win.”
This research had no specific funding. Dr. Fong and Dr. Lim had no relevant disclosures. Dr. Kurian disclosed relationships with Allergan, Allurion, CineMed, CSATS, Ezisurg Medical, Hernon, Johnson & Johnson, Medtronic, Novo, Stryker, and Vivus.
A version of this article appeared on Medscape.com.
Bariatric surgery appears to decrease the risk for some cancers, but it may increase the risk for others, particularly colorectal cancer (CRC), according to a synthesis of current evidence.
“There has been a recent burst of studies examining the association between bariatric surgery and the longitudinal risks of developing cancer,” corresponding author Zhi Ven Fong, MD, MPH, DrPH, surgical oncologist, Mayo Clinic Arizona, Phoenix, said in an interview. “However, there has not been a rigorous and critical analysis of the data published to date.”
In evaluating research showing an association between bariatric surgery and longitudinal cancer risk, the investigators found that the quality of the studies and their findings are “heterogeneous and might be susceptible to bias,” Dr. Fong said.
Bariatric surgery appears to have the strongest and most consistent association with the reduction of breast, ovarian, and endometrial cancer risk, first author Pei-Wen Lim, MD, MS, bariatric surgeon at Mayo Clinic Arizona, Phoenix, told this news organization. “However, there have been concerning signals from preclinical and epidemiological studies that bariatric surgery may be associated with a higher risk of developing colorectal cancers,” she added.
The authors cautioned against certain changes in clinical management.
“First, cancer surveillance frequency should not be altered after bariatric surgery because of any assumed reduction in longitudinal cancer risk, and surveillance strategy should mirror that of an average-risk individual,” they wrote. “Secondly, the indications for bariatric surgery should not be expanded for the purpose of cancer-risk mitigation.”
The review was published online in JAMA Surgery.
Protection Against Hormone-Related Cancers
The authors pointed to several studies that appear to support the association between bariatric surgery and decreased risk for hormone-related cancers.
Among them is an observational study of 6781 patients in Canada that showed a significant reduction in breast cancer risk at a median follow-up of 5 years in those who had bariatric surgery vs those who did not (P = .01).
The largest study to date on risk for hormone-related cancer after bariatric surgery was conducted using New York State data for 302,883 women.
It showed a lower rate of breast, endometrial, and ovarian cancers after bariatric surgery (hazard ratio [HR], 0.78; P < .001), with Roux-en-Y gastric bypass conferring the greatest benefit compared with laparoscopic sleeve gastrectomy (HR, 0.66; P = .006) and laparoscopic adjustable gastric banding (HR, 0.83; P = .006).
Beyond the shared mechanisms explaining obesity and cancer risk, a proposed explanation for the strong, consistent association between bariatric surgery and hormone-sensitive cancers is the role obesity-related changes in estrogen stimulation play in development of such cancers, the authors noted.
Association With GI Cancers
The association between bariatric surgery and development of esophageal, gastric, liver, and pancreas cancers is less clear. The data are heterogeneous, with studies showing either no association or decreased longitudinal incidence, the authors reported.
The data are also mixed when it comes to CRC. Epidemiological studies have demonstrated decreased longitudinal incidence of colon and rectal cancer after bariatric surgery; however, two studies have suggested an increased CRC risk after bariatric surgery, the authors noted.
A 15-year study from England that matched 8794 patients with obesity who underwent bariatric surgery with 8794 patients with obesity who did not have the surgery showed that gastric bypass (but not gastric banding or sleeve gastrectomy) was associated with a greater than twofold increased risk of developing colon and rectal cancer (odds ratio, 2.63).
These findings were corroborated in a Swedish cohort study with more than 10 years of follow-up data.
One potential explanation for the heterogeneous findings is that “present studies do not discriminate the sub-types of colon and rectal cancer, with bariatric surgery possibly increasing the incidence of colitis-associated cancers but not hereditary cancers,” the authors wrote.
“The mechanism by which gastric bypass may increase the risk of colorectal cancer is through changes in the gut’s microbiome. These changes in gut flora may triumph the protective effect of weight loss on the development of colorectal cancers,” Dr. Fong said.
Prospective studies are necessary to better delineate CRC risk after bariatric surgery, the authors wrote.
Benefits Outweigh Risk
“Ultimately, it has been proven that bariatric surgery saves lives by improving the metabolic profile of patients with obesity through reduction in cardiovascular risk factors such as hypertension, diabetes, and nonalcoholic fatty liver disease,” Dr. Lim said.
“If patients qualify for bariatric surgery on the basis of their BMI or comorbidities, they should pursue it for its metabolic benefits, but perhaps consider timely or closer-interval screening colonoscopies to monitor for potential colorectal cancer development,” Dr. Lim added.
When asked to comment on the review, Marina Kurian, MD, president, American Society for Metabolic and Bariatric Surgery, also pointed to the advantages of bariatric surgery in reducing major adverse cardiovascular events and improving hypertension, hyperlipidemia, and diabetes.
Bariatric surgery reduces many types of cancers, although the data specific to CRC risk with bariatric surgery are mixed, she added.
“The jury is still out,” said Dr. Kurian, clinical professor of surgery at NYU Langone Health in New York, who was not involved in the review. “There are papers and meta-analyses that show benefit even in colorectal cancer, but then there are a couple of papers out there that suggest a risk that seems to be specific to men.
“It could just be a numbers game, where we may not have enough data. We need more granular data that will help address these nuances and really determine what is the actual risk,” Dr. Kurian said. “But overall, for cancer, bariatric surgery is a win.”
This research had no specific funding. Dr. Fong and Dr. Lim had no relevant disclosures. Dr. Kurian disclosed relationships with Allergan, Allurion, CineMed, CSATS, Ezisurg Medical, Hernon, Johnson & Johnson, Medtronic, Novo, Stryker, and Vivus.
A version of this article appeared on Medscape.com.