Colon and Rectal

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

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

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

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

 

Study Tracked 97 Dietary Factors

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

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

 

Calcium Intake Showed the Strongest Protective Association

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

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

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

 

Alcohol and Processed Meat Confirmed as Risk Factors

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

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

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

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

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

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

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

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

 

Study Tracked 97 Dietary Factors

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

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

 

Calcium Intake Showed the Strongest Protective Association

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

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

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

 

Alcohol and Processed Meat Confirmed as Risk Factors

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

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

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

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

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

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

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

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

 

Study Tracked 97 Dietary Factors

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

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

 

Calcium Intake Showed the Strongest Protective Association

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

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

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

 

Alcohol and Processed Meat Confirmed as Risk Factors

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

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

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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

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

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

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

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

 

Study Details

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

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

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

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

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

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

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

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

 

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

 

Study Details

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

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

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

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

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

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

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

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

 

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

 

Study Details

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

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

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

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

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

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

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

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

 

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

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

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

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

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

A version of this article appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.

This is an issue that we must address, I think, epidemiologically. We know that early-onset colorectal cancer is defined as a disease arising in those under the age of 50. There’s been a very sharp increase globally over the past 20-30 years, and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.

The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease. 

There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.

The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.

Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.

They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age. 

All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later. 

This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it. 

Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.

More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology. 

I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.

This is an issue that we must address, I think, epidemiologically. We know that early-onset colorectal cancer is defined as a disease arising in those under the age of 50. There’s been a very sharp increase globally over the past 20-30 years, and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.

The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease. 

There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.

The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.

Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.

They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age. 

All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later. 

This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it. 

Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.

More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology. 

I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.

This is an issue that we must address, I think, epidemiologically. We know that early-onset colorectal cancer is defined as a disease arising in those under the age of 50. There’s been a very sharp increase globally over the past 20-30 years, and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.

The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease. 

There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.

The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.

Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.

They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age. 

All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later. 

This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it. 

Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.

More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology. 

I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche. 

A version of this article appeared on Medscape.com.

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.

The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.

In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).

The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.

The analysis did not stop there in defining the optimal upfront therapy for this patient population.

In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.

Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.

In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.

Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.

 

Why Does This Clarity Matter?

The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.

In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.

As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.

Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.

Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.

Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.

The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.

Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.

Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).

ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.

CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.

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

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.

The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.

In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).

The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.

The analysis did not stop there in defining the optimal upfront therapy for this patient population.

In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.

Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.

In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.

Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.

 

Why Does This Clarity Matter?

The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.

In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.

As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.

Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.

Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.

Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.

The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.

Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.

Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).

ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.

CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.

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

What is the best upfront chemotherapy option for patients with colorectal cancer (CRC) and unresectable liver metastases?

A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.

The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.

In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).

The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.

The analysis did not stop there in defining the optimal upfront therapy for this patient population.

In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.

Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.

In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.

Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.

 

Why Does This Clarity Matter?

The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.

In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.

As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.

Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.

Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.

Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.

The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.

Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.

Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).

ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.

CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.

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

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

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

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

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

TOPLINE:

Individuals with normal body mass index (BMI) measurements may still face an increased risk for colorectal cancer if they have central obesity, characterized by excess fat around the abdomen.

METHODOLOGY:

• General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
• Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
• Anthropometric measurements were performed using standardized methods.
• Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.

TAKEAWAY:

• Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
• During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
• Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
• After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
• WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
• Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.

IN PRACTICE:

“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.

SOURCE:

The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.

LIMITATIONS:

This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.

DISCLOSURES:

The authors declared no competing interests.

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

It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change. 

Did doctors adjust their screening practices? A recent study suggests that they have. Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.

Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.

Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.

This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.

In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas. 

Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.

Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.

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

It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change. 

Did doctors adjust their screening practices? A recent study suggests that they have. Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.

Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.

Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.

This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.

In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas. 

Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.

Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.

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

It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change. 

Did doctors adjust their screening practices? A recent study suggests that they have. Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.

Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.

Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.

This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.

In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas. 

Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.

Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.

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

TOPLINE:

After the US Preventive Services Task Force (USPSTF) in May 2021 lowered from 50 to 45 the recommended age to begin colorectal cancer (CRC) screening for average-risk adults, there was a threefold increase in screening rates among individuals aged 45-49, but disparities by socioeconomic status and locality occurred.

METHODOLOGY:

• Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
• They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
• They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.

TAKEAWAY:

• Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
• Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
• The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
• The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
• By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.

IN PRACTICE:

“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.

SOURCE:

The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open. 

LIMITATIONS:

Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.

DISCLOSURES:

The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.

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

TOPLINE:

After the US Preventive Services Task Force (USPSTF) in May 2021 lowered from 50 to 45 the recommended age to begin colorectal cancer (CRC) screening for average-risk adults, there was a threefold increase in screening rates among individuals aged 45-49, but disparities by socioeconomic status and locality occurred.

METHODOLOGY:

• Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
• They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
• They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.

TAKEAWAY:

• Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
• Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
• The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
• The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
• By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.

IN PRACTICE:

“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.

SOURCE:

The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open. 

LIMITATIONS:

Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.

DISCLOSURES:

The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.

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

TOPLINE:

After the US Preventive Services Task Force (USPSTF) in May 2021 lowered from 50 to 45 the recommended age to begin colorectal cancer (CRC) screening for average-risk adults, there was a threefold increase in screening rates among individuals aged 45-49, but disparities by socioeconomic status and locality occurred.

METHODOLOGY:

• Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
• They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
• They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.

TAKEAWAY:

• Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
• Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
• The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
• The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
• By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.

IN PRACTICE:

“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.

SOURCE:

The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open. 

LIMITATIONS:

Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.

DISCLOSURES:

The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.

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

TOPLINE:

Death rates for patients aged < 50 years with early-onset colorectal cancer (EOCRC) are higher in native Hawaiian and Other Pacific Islander individuals and non-Hispanic Black individuals than in non-Hispanic White individuals (adjusted hazard ratios [aHR] of 1.34 and 1.18, respectively). The largest racial and ethnic disparities in survival were linked to neighborhood socioeconomic status.

METHODOLOGY:

• US rates of EOCRC are increasing, with differences across racial and ethnic groups, but few studies have provided detailed risk estimates in the categories of Asian American and of Native Hawaiian or Other Pacific Islander, as well as the contribution of sociodemographic factors to these differences.
• A population-based cohort study analyzed California Cancer Registry data for 22,834 individuals aged 18-49 years diagnosed with EOCRC between January 2000 and December 2019.
• Researchers examined the association between mortality risk and racial and ethnic groups, including Asian American (15.5%, separated into seven subcategories), Hispanic (30.2%), Native Hawaiian or Other Pacific Islander (0.6%), non-Hispanic American Indian or Alaska Native (0.5%), non-Hispanic Black (7.3%), and non-Hispanic White (45.9%) individuals, with a median follow-up of 4.2 years.
• Statistical models measured baseline associations adjusting for clinical features and then tested for the contribution of socioeconomic factors together and separately, with adjustments for insurance status, neighborhood socioeconomic status, and more.

TAKEAWAY:

• Native Hawaiian or Other Pacific Islander individuals demonstrated the highest EOCRC mortality risk compared with non-Hispanic White individuals (socioeconomic status–adjusted HR [SES aHR], 1.34; 95% CI, 1.01-1.76).
• Non-Hispanic Black individuals showed a higher EOCRC mortality risk than non-Hispanic White individuals (SES aHR, 1.18; 95% CI, 1.07-1.29).
• Hispanic individuals’ higher EOCRC mortality (base aHR, 1.15; 95% CI, 1.08-1.22) disappeared after adjusting for neighborhood socioeconomic status (SES aHR, 0.98; 95% CI, 0.92-1.04).
• Southeast Asian individuals’ increased mortality risk (base aHR, 1.17; 95% CI, 1.03-1.34) was no longer significant after adjusting for insurance status (SES aHR, 1.10; 95% CI, 0.96-1.26).

IN PRACTICE:

“As clinicians and researchers, we should ask ourselves how to act on these findings,” wrote the authors of an invited commentary. “The effort cannot stop with data analysis alone, it must extend to actionable steps,” such as tailored efforts to deliver culturally competent care and patient navigation services to those with greatest need and at highest risk, they added.

SOURCE:

The study was led by Joshua Demb, PhD, University of California, San Diego. The study was published online on November 22 in JAMA Network Open (2024. doi: 10.1001/jamanetworkopen.2024.46820) with the invited commentary led by Clare E. Jacobson, MD, University of Michigan, Ann Arbor.

LIMITATIONS:

The study was limited by a relatively short follow-up time and small sample sizes in some racial and ethnic groups, potentially leading to imprecise aHR estimates. The generalizability of findings beyond California requires further investigation, and the ability to examine potential associations between neighborhood socioeconomic status and other factors was also constrained by small sample sizes.

DISCLOSURES:

The study received support from the National Cancer Institute at the National Institutes of Health. One study author reported receiving consulting fees from Guardant Health, InterVenn Biosciences, Geneoscopy, and Universal DX; research support from Freenome; and stock options from CellMax outside the submitted work. No other disclosures were reported by other authors of the study or the commentary.

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

TOPLINE:

Death rates for patients aged < 50 years with early-onset colorectal cancer (EOCRC) are higher in native Hawaiian and Other Pacific Islander individuals and non-Hispanic Black individuals than in non-Hispanic White individuals (adjusted hazard ratios [aHR] of 1.34 and 1.18, respectively). The largest racial and ethnic disparities in survival were linked to neighborhood socioeconomic status.

METHODOLOGY:

• US rates of EOCRC are increasing, with differences across racial and ethnic groups, but few studies have provided detailed risk estimates in the categories of Asian American and of Native Hawaiian or Other Pacific Islander, as well as the contribution of sociodemographic factors to these differences.
• A population-based cohort study analyzed California Cancer Registry data for 22,834 individuals aged 18-49 years diagnosed with EOCRC between January 2000 and December 2019.
• Researchers examined the association between mortality risk and racial and ethnic groups, including Asian American (15.5%, separated into seven subcategories), Hispanic (30.2%), Native Hawaiian or Other Pacific Islander (0.6%), non-Hispanic American Indian or Alaska Native (0.5%), non-Hispanic Black (7.3%), and non-Hispanic White (45.9%) individuals, with a median follow-up of 4.2 years.
• Statistical models measured baseline associations adjusting for clinical features and then tested for the contribution of socioeconomic factors together and separately, with adjustments for insurance status, neighborhood socioeconomic status, and more.

TAKEAWAY:

• Native Hawaiian or Other Pacific Islander individuals demonstrated the highest EOCRC mortality risk compared with non-Hispanic White individuals (socioeconomic status–adjusted HR [SES aHR], 1.34; 95% CI, 1.01-1.76).
• Non-Hispanic Black individuals showed a higher EOCRC mortality risk than non-Hispanic White individuals (SES aHR, 1.18; 95% CI, 1.07-1.29).
• Hispanic individuals’ higher EOCRC mortality (base aHR, 1.15; 95% CI, 1.08-1.22) disappeared after adjusting for neighborhood socioeconomic status (SES aHR, 0.98; 95% CI, 0.92-1.04).
• Southeast Asian individuals’ increased mortality risk (base aHR, 1.17; 95% CI, 1.03-1.34) was no longer significant after adjusting for insurance status (SES aHR, 1.10; 95% CI, 0.96-1.26).

IN PRACTICE:

“As clinicians and researchers, we should ask ourselves how to act on these findings,” wrote the authors of an invited commentary. “The effort cannot stop with data analysis alone, it must extend to actionable steps,” such as tailored efforts to deliver culturally competent care and patient navigation services to those with greatest need and at highest risk, they added.

SOURCE:

The study was led by Joshua Demb, PhD, University of California, San Diego. The study was published online on November 22 in JAMA Network Open (2024. doi: 10.1001/jamanetworkopen.2024.46820) with the invited commentary led by Clare E. Jacobson, MD, University of Michigan, Ann Arbor.

LIMITATIONS:

The study was limited by a relatively short follow-up time and small sample sizes in some racial and ethnic groups, potentially leading to imprecise aHR estimates. The generalizability of findings beyond California requires further investigation, and the ability to examine potential associations between neighborhood socioeconomic status and other factors was also constrained by small sample sizes.

DISCLOSURES:

The study received support from the National Cancer Institute at the National Institutes of Health. One study author reported receiving consulting fees from Guardant Health, InterVenn Biosciences, Geneoscopy, and Universal DX; research support from Freenome; and stock options from CellMax outside the submitted work. No other disclosures were reported by other authors of the study or the commentary.

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

TOPLINE:

Death rates for patients aged < 50 years with early-onset colorectal cancer (EOCRC) are higher in native Hawaiian and Other Pacific Islander individuals and non-Hispanic Black individuals than in non-Hispanic White individuals (adjusted hazard ratios [aHR] of 1.34 and 1.18, respectively). The largest racial and ethnic disparities in survival were linked to neighborhood socioeconomic status.

METHODOLOGY:

• US rates of EOCRC are increasing, with differences across racial and ethnic groups, but few studies have provided detailed risk estimates in the categories of Asian American and of Native Hawaiian or Other Pacific Islander, as well as the contribution of sociodemographic factors to these differences.
• A population-based cohort study analyzed California Cancer Registry data for 22,834 individuals aged 18-49 years diagnosed with EOCRC between January 2000 and December 2019.
• Researchers examined the association between mortality risk and racial and ethnic groups, including Asian American (15.5%, separated into seven subcategories), Hispanic (30.2%), Native Hawaiian or Other Pacific Islander (0.6%), non-Hispanic American Indian or Alaska Native (0.5%), non-Hispanic Black (7.3%), and non-Hispanic White (45.9%) individuals, with a median follow-up of 4.2 years.
• Statistical models measured baseline associations adjusting for clinical features and then tested for the contribution of socioeconomic factors together and separately, with adjustments for insurance status, neighborhood socioeconomic status, and more.

TAKEAWAY:

• Native Hawaiian or Other Pacific Islander individuals demonstrated the highest EOCRC mortality risk compared with non-Hispanic White individuals (socioeconomic status–adjusted HR [SES aHR], 1.34; 95% CI, 1.01-1.76).
• Non-Hispanic Black individuals showed a higher EOCRC mortality risk than non-Hispanic White individuals (SES aHR, 1.18; 95% CI, 1.07-1.29).
• Hispanic individuals’ higher EOCRC mortality (base aHR, 1.15; 95% CI, 1.08-1.22) disappeared after adjusting for neighborhood socioeconomic status (SES aHR, 0.98; 95% CI, 0.92-1.04).
• Southeast Asian individuals’ increased mortality risk (base aHR, 1.17; 95% CI, 1.03-1.34) was no longer significant after adjusting for insurance status (SES aHR, 1.10; 95% CI, 0.96-1.26).

IN PRACTICE:

“As clinicians and researchers, we should ask ourselves how to act on these findings,” wrote the authors of an invited commentary. “The effort cannot stop with data analysis alone, it must extend to actionable steps,” such as tailored efforts to deliver culturally competent care and patient navigation services to those with greatest need and at highest risk, they added.

SOURCE:

The study was led by Joshua Demb, PhD, University of California, San Diego. The study was published online on November 22 in JAMA Network Open (2024. doi: 10.1001/jamanetworkopen.2024.46820) with the invited commentary led by Clare E. Jacobson, MD, University of Michigan, Ann Arbor.

LIMITATIONS:

The study was limited by a relatively short follow-up time and small sample sizes in some racial and ethnic groups, potentially leading to imprecise aHR estimates. The generalizability of findings beyond California requires further investigation, and the ability to examine potential associations between neighborhood socioeconomic status and other factors was also constrained by small sample sizes.

DISCLOSURES:

The study received support from the National Cancer Institute at the National Institutes of Health. One study author reported receiving consulting fees from Guardant Health, InterVenn Biosciences, Geneoscopy, and Universal DX; research support from Freenome; and stock options from CellMax outside the submitted work. No other disclosures were reported by other authors of the study or the commentary.

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