For more information about the American Gastroenterological Association’s upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.
 

Upcoming Events

May 1, 2021
2021 AGA Postgraduate Course (Virtual Event)
Discover emerging science, leverage new tools and technologies and build lasting collaborations that will transform GI research and patient care at the AGA Postgraduate Course. Receive updates here.

May 21-23, 2021
Digestive Disease Week® (Virtual Event)
Save the date for the world’s leading event in digestive disease. DDW® brings professionals in gastroenterology, hepatology, endoscopy, and GI surgery together. Experience growth when you share your research, converge with trailblazers, and improve the lives of patients suffering from GI and liver diseases.

Early bird registration: Jan. 20 to Mar. 31, 2021.
 

Award Deadlines

AGA Student Abstract Award
This award supports recipients who are graduate students, medical students, or medical residents (residents up to postgraduate year 3) giving abstract-based oral or poster presentations at Digestive Disease Week® (DDW). The top scoring abstract will be designated the Student Abstract of the Year.

Application Deadline: Feb. 24, 2021
 

AGA–Moti L. & Kamla Rustgi International Travel Awards
This award provides support to early career (i.e., 35 years of age or younger at the time of Digestive Disease Week® (DDW)) basic, translational or clinical investigators residing outside North America giving abstract-based oral or poster presentations at DDW.

Application Deadline: Feb. 24, 2021
 

AGA Fellow Abstract Award
This award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations at Digestive Disease Week® (DDW). The top scoring abstract will be designated the Fellow Abstract of the Year.

Application Deadline: Feb. 24, 2021
 

AGA-Aman Armaan Ahmed Family Summer Undergraduate Research Fellowship (SURF)
These fellowships support undergraduate students from groups traditionally underrepresented in biomedical research to perform 10 weeks of research related to digestive diseases under the mentorship of top investigators in the fields of gastroenterology and hepatology. The award provides a stipend, funding to offset travel and meal expenses, and opportunities to learn about future training and career options.

Application Deadline: Feb. 24, 2021

For more information about the American Gastroenterological Association’s upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.
 

Upcoming Events

May 1, 2021
2021 AGA Postgraduate Course (Virtual Event)
Discover emerging science, leverage new tools and technologies and build lasting collaborations that will transform GI research and patient care at the AGA Postgraduate Course. Receive updates here.

May 21-23, 2021
Digestive Disease Week® (Virtual Event)
Save the date for the world’s leading event in digestive disease. DDW® brings professionals in gastroenterology, hepatology, endoscopy, and GI surgery together. Experience growth when you share your research, converge with trailblazers, and improve the lives of patients suffering from GI and liver diseases.

Early bird registration: Jan. 20 to Mar. 31, 2021.
 

Award Deadlines

AGA Student Abstract Award
This award supports recipients who are graduate students, medical students, or medical residents (residents up to postgraduate year 3) giving abstract-based oral or poster presentations at Digestive Disease Week® (DDW). The top scoring abstract will be designated the Student Abstract of the Year.

Application Deadline: Feb. 24, 2021
 

AGA–Moti L. & Kamla Rustgi International Travel Awards
This award provides support to early career (i.e., 35 years of age or younger at the time of Digestive Disease Week® (DDW)) basic, translational or clinical investigators residing outside North America giving abstract-based oral or poster presentations at DDW.

Application Deadline: Feb. 24, 2021
 

AGA Fellow Abstract Award
This award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations at Digestive Disease Week® (DDW). The top scoring abstract will be designated the Fellow Abstract of the Year.

Application Deadline: Feb. 24, 2021
 

AGA-Aman Armaan Ahmed Family Summer Undergraduate Research Fellowship (SURF)
These fellowships support undergraduate students from groups traditionally underrepresented in biomedical research to perform 10 weeks of research related to digestive diseases under the mentorship of top investigators in the fields of gastroenterology and hepatology. The award provides a stipend, funding to offset travel and meal expenses, and opportunities to learn about future training and career options.

Application Deadline: Feb. 24, 2021

For more information about the American Gastroenterological Association’s upcoming events and award deadlines, please visit http://agau.gastro.org and http://www.gastro.org/research-funding.
 

Upcoming Events

May 1, 2021
2021 AGA Postgraduate Course (Virtual Event)
Discover emerging science, leverage new tools and technologies and build lasting collaborations that will transform GI research and patient care at the AGA Postgraduate Course. Receive updates here.

May 21-23, 2021
Digestive Disease Week® (Virtual Event)
Save the date for the world’s leading event in digestive disease. DDW® brings professionals in gastroenterology, hepatology, endoscopy, and GI surgery together. Experience growth when you share your research, converge with trailblazers, and improve the lives of patients suffering from GI and liver diseases.

Early bird registration: Jan. 20 to Mar. 31, 2021.
 

Award Deadlines

AGA Student Abstract Award
This award supports recipients who are graduate students, medical students, or medical residents (residents up to postgraduate year 3) giving abstract-based oral or poster presentations at Digestive Disease Week® (DDW). The top scoring abstract will be designated the Student Abstract of the Year.

Application Deadline: Feb. 24, 2021
 

AGA–Moti L. & Kamla Rustgi International Travel Awards
This award provides support to early career (i.e., 35 years of age or younger at the time of Digestive Disease Week® (DDW)) basic, translational or clinical investigators residing outside North America giving abstract-based oral or poster presentations at DDW.

Application Deadline: Feb. 24, 2021
 

AGA Fellow Abstract Award
This award supports recipients who are MD, PhD, or equivalent fellows giving abstract-based oral or poster presentations at Digestive Disease Week® (DDW). The top scoring abstract will be designated the Fellow Abstract of the Year.

Application Deadline: Feb. 24, 2021
 

AGA-Aman Armaan Ahmed Family Summer Undergraduate Research Fellowship (SURF)
These fellowships support undergraduate students from groups traditionally underrepresented in biomedical research to perform 10 weeks of research related to digestive diseases under the mentorship of top investigators in the fields of gastroenterology and hepatology. The award provides a stipend, funding to offset travel and meal expenses, and opportunities to learn about future training and career options.

Application Deadline: Feb. 24, 2021

Key clinical point: Mindfulness-based stress reduction (MBSR) did not improve migraine frequency more than headache education as both groups had similar decreases; however, mindfulness meditation may help treat the total burden of migraine.

Major finding: Decrease in headache frequency did not differ between the 2 groups (MBSR, −2.0 vs headache education, −2.4; P = .52). The MBSR vs. headache education group had significantly greater improvements at 36 weeks in disability (P less than .001), quality of life (P =.01), self-efficacy (P = .04), pain catastrophizing (P less than .001), depression scores (P =.008), decrease in pain intensity (P =.004), and decrease in pain unpleasantness (P =.005).

Study details: In this double-blinded, randomized clinical trial, 89 adults with a history of migraine were assigned to receive training in MBSR/yoga (n=45) or health education instruction on headaches, pathophysiology, triggers, stress, and treatment approaches (n=44).

Disclosures: This study was funded by an American Pain Society Grant from the Sharon S. Keller Chronic Pain Research Program and the National Center for Complementary and Integrative Health. RE Wells and F Zeidan reported grants from the National Institutes of Health. TT Houle reported receiving personal fees from GlaxoSmithKline, Eli Lilly, and StatReviewer. The remaining authors declared no conflicts of interest.

Source: Wells RE et al. JAMA Intern Med. 2020 Dec 14. doi: 10.1001/jamainternmed.2020.7090.

Key clinical point: Mindfulness-based stress reduction (MBSR) did not improve migraine frequency more than headache education as both groups had similar decreases; however, mindfulness meditation may help treat the total burden of migraine.

Major finding: Decrease in headache frequency did not differ between the 2 groups (MBSR, −2.0 vs headache education, −2.4; P = .52). The MBSR vs. headache education group had significantly greater improvements at 36 weeks in disability (P less than .001), quality of life (P =.01), self-efficacy (P = .04), pain catastrophizing (P less than .001), depression scores (P =.008), decrease in pain intensity (P =.004), and decrease in pain unpleasantness (P =.005).

Study details: In this double-blinded, randomized clinical trial, 89 adults with a history of migraine were assigned to receive training in MBSR/yoga (n=45) or health education instruction on headaches, pathophysiology, triggers, stress, and treatment approaches (n=44).

Disclosures: This study was funded by an American Pain Society Grant from the Sharon S. Keller Chronic Pain Research Program and the National Center for Complementary and Integrative Health. RE Wells and F Zeidan reported grants from the National Institutes of Health. TT Houle reported receiving personal fees from GlaxoSmithKline, Eli Lilly, and StatReviewer. The remaining authors declared no conflicts of interest.

Source: Wells RE et al. JAMA Intern Med. 2020 Dec 14. doi: 10.1001/jamainternmed.2020.7090.

Key clinical point: Mindfulness-based stress reduction (MBSR) did not improve migraine frequency more than headache education as both groups had similar decreases; however, mindfulness meditation may help treat the total burden of migraine.

Major finding: Decrease in headache frequency did not differ between the 2 groups (MBSR, −2.0 vs headache education, −2.4; P = .52). The MBSR vs. headache education group had significantly greater improvements at 36 weeks in disability (P less than .001), quality of life (P =.01), self-efficacy (P = .04), pain catastrophizing (P less than .001), depression scores (P =.008), decrease in pain intensity (P =.004), and decrease in pain unpleasantness (P =.005).

Study details: In this double-blinded, randomized clinical trial, 89 adults with a history of migraine were assigned to receive training in MBSR/yoga (n=45) or health education instruction on headaches, pathophysiology, triggers, stress, and treatment approaches (n=44).

Disclosures: This study was funded by an American Pain Society Grant from the Sharon S. Keller Chronic Pain Research Program and the National Center for Complementary and Integrative Health. RE Wells and F Zeidan reported grants from the National Institutes of Health. TT Houle reported receiving personal fees from GlaxoSmithKline, Eli Lilly, and StatReviewer. The remaining authors declared no conflicts of interest.

Source: Wells RE et al. JAMA Intern Med. 2020 Dec 14. doi: 10.1001/jamainternmed.2020.7090.

Key clinical point: Delivery by cesarean section is not associated with migraine later in life. However, cesarean section is associated with a modestly reduced risk of non-migrainous headache.

Major finding: Delivery by cesarean section was not associated with later development of migraine (adjusted odds ratio [aOR], 0.93; P = .63). A negative association was seen between cesarean section and non-migrainous headache (aOR, 0.77; P = .04).

Study details: The findings are based on a retrospective register-linked HUNT population cohort study of 11,194 participants (age, 19-41 years; migraine group, n=1,855 and non-migrainous headache group, n=3,358).

Disclosures: This study was supported by grants from the University of Oslo, Akershus University Hospital, and Oslo University Hospital. The authors declared no conflicts of interest.

Source: Kristoffersen ES et al. BMJ Open. 2020 Nov 18. doi: 10.1136/bmjopen-2020-040685.

Key clinical point: Delivery by cesarean section is not associated with migraine later in life. However, cesarean section is associated with a modestly reduced risk of non-migrainous headache.

Major finding: Delivery by cesarean section was not associated with later development of migraine (adjusted odds ratio [aOR], 0.93; P = .63). A negative association was seen between cesarean section and non-migrainous headache (aOR, 0.77; P = .04).

Study details: The findings are based on a retrospective register-linked HUNT population cohort study of 11,194 participants (age, 19-41 years; migraine group, n=1,855 and non-migrainous headache group, n=3,358).

Disclosures: This study was supported by grants from the University of Oslo, Akershus University Hospital, and Oslo University Hospital. The authors declared no conflicts of interest.

Source: Kristoffersen ES et al. BMJ Open. 2020 Nov 18. doi: 10.1136/bmjopen-2020-040685.

Key clinical point: Delivery by cesarean section is not associated with migraine later in life. However, cesarean section is associated with a modestly reduced risk of non-migrainous headache.

Major finding: Delivery by cesarean section was not associated with later development of migraine (adjusted odds ratio [aOR], 0.93; P = .63). A negative association was seen between cesarean section and non-migrainous headache (aOR, 0.77; P = .04).

Study details: The findings are based on a retrospective register-linked HUNT population cohort study of 11,194 participants (age, 19-41 years; migraine group, n=1,855 and non-migrainous headache group, n=3,358).

Disclosures: This study was supported by grants from the University of Oslo, Akershus University Hospital, and Oslo University Hospital. The authors declared no conflicts of interest.

Source: Kristoffersen ES et al. BMJ Open. 2020 Nov 18. doi: 10.1136/bmjopen-2020-040685.

Key clinical point: In adults with episodic migraine, intravenous eptinezumab administered every 12 weeks for up to 4 doses provides early and sustained migraine preventive efficacy and is well tolerated with an acceptable safety profile.

Major finding: The reduction in mean monthly migraine days was maintained with eptinezumab throughout the study period (100 mg: −3.9, −4.5, −4.7, and −4.5 days; 300 mg: −4.3, −4.8, −5.1, and −5.3 days; and placebo: −3.2, −3.8, −4.0, and −4.0 days during weeks 1-12, 13-24, 25-36, and 37-48, respectively). The percentage of patients with a reduction of 50% or greater and 75% or greater in migraine for each 12-week interval was consistently higher in the eptinezumab group vs. placebo group. Adverse events were similar across dosing periods.

Study details: Results of phase 3 PROMISE-1 through 1 year of treatment (up to 4 doses). In PROMISE-1, 888 patients with episodic migraine were randomly assigned in a ratio of 1:1:1:1 to receive eptinezumab 30 mg, 100 mg, 300 mg, or placebo every 12 weeks.

Disclosures: No study sponsor was identified. The presenting author has been a consultant and/or scientific advisor for Alder/Lundbeck, Amgen, Biohaven, Eli Lilly, Impel Neuropharma, and Theranica, and has received research support from Alder/Lundbeck, Allergan, Amgen, Biohaven, Charleston Labs, Eli Lilly, Electrocore, Novartis, Novo Nordisk, Satsuma, Theranica, and Vorso.

Source: Smith TR et al. Clin Ther. 2020 Nov 27. doi: 10.1016/j.clinthera.2020.11.007.

Key clinical point: In adults with episodic migraine, intravenous eptinezumab administered every 12 weeks for up to 4 doses provides early and sustained migraine preventive efficacy and is well tolerated with an acceptable safety profile.

Major finding: The reduction in mean monthly migraine days was maintained with eptinezumab throughout the study period (100 mg: −3.9, −4.5, −4.7, and −4.5 days; 300 mg: −4.3, −4.8, −5.1, and −5.3 days; and placebo: −3.2, −3.8, −4.0, and −4.0 days during weeks 1-12, 13-24, 25-36, and 37-48, respectively). The percentage of patients with a reduction of 50% or greater and 75% or greater in migraine for each 12-week interval was consistently higher in the eptinezumab group vs. placebo group. Adverse events were similar across dosing periods.

Study details: Results of phase 3 PROMISE-1 through 1 year of treatment (up to 4 doses). In PROMISE-1, 888 patients with episodic migraine were randomly assigned in a ratio of 1:1:1:1 to receive eptinezumab 30 mg, 100 mg, 300 mg, or placebo every 12 weeks.

Disclosures: No study sponsor was identified. The presenting author has been a consultant and/or scientific advisor for Alder/Lundbeck, Amgen, Biohaven, Eli Lilly, Impel Neuropharma, and Theranica, and has received research support from Alder/Lundbeck, Allergan, Amgen, Biohaven, Charleston Labs, Eli Lilly, Electrocore, Novartis, Novo Nordisk, Satsuma, Theranica, and Vorso.

Source: Smith TR et al. Clin Ther. 2020 Nov 27. doi: 10.1016/j.clinthera.2020.11.007.

Key clinical point: In adults with episodic migraine, intravenous eptinezumab administered every 12 weeks for up to 4 doses provides early and sustained migraine preventive efficacy and is well tolerated with an acceptable safety profile.

Major finding: The reduction in mean monthly migraine days was maintained with eptinezumab throughout the study period (100 mg: −3.9, −4.5, −4.7, and −4.5 days; 300 mg: −4.3, −4.8, −5.1, and −5.3 days; and placebo: −3.2, −3.8, −4.0, and −4.0 days during weeks 1-12, 13-24, 25-36, and 37-48, respectively). The percentage of patients with a reduction of 50% or greater and 75% or greater in migraine for each 12-week interval was consistently higher in the eptinezumab group vs. placebo group. Adverse events were similar across dosing periods.

Study details: Results of phase 3 PROMISE-1 through 1 year of treatment (up to 4 doses). In PROMISE-1, 888 patients with episodic migraine were randomly assigned in a ratio of 1:1:1:1 to receive eptinezumab 30 mg, 100 mg, 300 mg, or placebo every 12 weeks.

Disclosures: No study sponsor was identified. The presenting author has been a consultant and/or scientific advisor for Alder/Lundbeck, Amgen, Biohaven, Eli Lilly, Impel Neuropharma, and Theranica, and has received research support from Alder/Lundbeck, Allergan, Amgen, Biohaven, Charleston Labs, Eli Lilly, Electrocore, Novartis, Novo Nordisk, Satsuma, Theranica, and Vorso.

Source: Smith TR et al. Clin Ther. 2020 Nov 27. doi: 10.1016/j.clinthera.2020.11.007.

Key clinical point: Rimegepant was effective and had favourable safety and tolerability profiles in the preventive treatment of migraine.

Major finding: Rimegepant was superior to placebo in terms of change in the mean number of migraine days per month during weeks 9-12 (−4.3 days vs. −3.5 days; least squares mean difference, −0.8 days; P = .0099). Adverse events were reported by 133 of the patients who received rimegepant and 133 participants in the placebo group.

Study details: A multicentre, phase 2/3, randomised, double-blind, placebo-controlled trial of 695 participants randomly assigned to receive oral rimegepant 75 mg (n = 348) or matching placebo (n=347) every other day for 12 weeks. The safety analysis included 741 participants, who received at least one dose of study medication.

Disclosures: The study was funded by Biohaven Pharmaceuticals. Some study investigators reported owning stock in, being an employee of, receiving support/grant from Biohaven Pharmaceuticals.

Source: Croop R et al. Lancet. 2020 Dec 15. doi: 10.1016/S0140-6736(20)32544-7.

Key clinical point: Rimegepant was effective and had favourable safety and tolerability profiles in the preventive treatment of migraine.

Major finding: Rimegepant was superior to placebo in terms of change in the mean number of migraine days per month during weeks 9-12 (−4.3 days vs. −3.5 days; least squares mean difference, −0.8 days; P = .0099). Adverse events were reported by 133 of the patients who received rimegepant and 133 participants in the placebo group.

Study details: A multicentre, phase 2/3, randomised, double-blind, placebo-controlled trial of 695 participants randomly assigned to receive oral rimegepant 75 mg (n = 348) or matching placebo (n=347) every other day for 12 weeks. The safety analysis included 741 participants, who received at least one dose of study medication.

Disclosures: The study was funded by Biohaven Pharmaceuticals. Some study investigators reported owning stock in, being an employee of, receiving support/grant from Biohaven Pharmaceuticals.

Source: Croop R et al. Lancet. 2020 Dec 15. doi: 10.1016/S0140-6736(20)32544-7.

Key clinical point: Rimegepant was effective and had favourable safety and tolerability profiles in the preventive treatment of migraine.

Major finding: Rimegepant was superior to placebo in terms of change in the mean number of migraine days per month during weeks 9-12 (−4.3 days vs. −3.5 days; least squares mean difference, −0.8 days; P = .0099). Adverse events were reported by 133 of the patients who received rimegepant and 133 participants in the placebo group.

Study details: A multicentre, phase 2/3, randomised, double-blind, placebo-controlled trial of 695 participants randomly assigned to receive oral rimegepant 75 mg (n = 348) or matching placebo (n=347) every other day for 12 weeks. The safety analysis included 741 participants, who received at least one dose of study medication.

Disclosures: The study was funded by Biohaven Pharmaceuticals. Some study investigators reported owning stock in, being an employee of, receiving support/grant from Biohaven Pharmaceuticals.

Source: Croop R et al. Lancet. 2020 Dec 15. doi: 10.1016/S0140-6736(20)32544-7.

The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online Dec. 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explained.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” wrote the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggested.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,”  Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard Medical School, Boston, wrote in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock ... directly translates to a higher risk of colorectal cancer,” they noted.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they pointed out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m² vs 28.29 kg/m²).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists wrote.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators said.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

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

The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online Dec. 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explained.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” wrote the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggested.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,”  Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard Medical School, Boston, wrote in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock ... directly translates to a higher risk of colorectal cancer,” they noted.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they pointed out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m² vs 28.29 kg/m²).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists wrote.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators said.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

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

The right colon appears to age faster in Black people than in White people, perhaps explaining the higher prevalence of right-side colon cancer among Black Americans, according to results from a biopsy study.

The findings were published online Dec. 30 in the Journal of the National Cancer Institute.

For the study, investigators analyzed colon biopsy specimens from 128 individuals who underwent routine colorectal screening.

The researchers compared DNA methylation levels in right and left colon biopsy samples from the same patient. They then assigned epigenetic ages to the tissue samples using the Hovarth clock, which estimates tissue age on the basis of DNA methylation.

DNA methylation is influenced by age and environmental exposures. Aberrant DNA methylation is a hallmark of colorectal cancer, the researchers explained.

The epigenetic age of the right colon of the 88 Black patients was 1.51 years ahead of their left colon; the right colon of the 44 White patients was epigenetically 1.93 years younger than their left colon.

The right colon was epigenetically older than the left colon in 60.2% of Black patients; it was younger in more than 70% of White patients.

A unique pattern of DNA hypermethylation was found in the right colon of Black patients.

“Our results provide biological plausibility for the observed relative preponderance of right colon cancer and younger age of onset in African Americans as compared to European Americans,” wrote the investigators, led by Matthew Devall, PhD, a research associate at the Center for Public Health Genomics at the University of Virginia, Charlottesville.

“Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC [colorectal cancer] burden,” they suggested.

If these findings are “corroborated in African Americans in future studies, these results could potentially explain racial differences in the site predilection of colorectal cancers,”  Amit Joshi, MBBS, PhD, and Andrew Chan, MD, gastrointestinal molecular epidemiologists at Harvard Medical School, Boston, wrote in an accompanying editorial.

However, “it is not clear if the higher epigenetic aging measured using the Horvath clock ... directly translates to a higher risk of colorectal cancer,” they noted.

Some differences between the Black patients and the White patients in the study could explain the methylation differences, they pointed out. A higher proportion of Black patients smoked (37.5% vs. 15%), and Black patients were younger (median age, 55.5 years, vs. 61.7 years). In addition, the study included more Black women than White women (67% vs. 58%), and body mass indexes were higher for Black patients than White patients (31.36 kg/m² vs 28.29 kg/m²).

“One or more of these factors, or others that were not measured, may be linked to differential methylation in the right compared with left colon,” the editorialists wrote.

Even so, among the Black patients, almost 70% of differentially methylated positions in the right colon were hypermethylated, compared to less than half in the left colon. These included positions previously associated with colorectal cancer, aging, and ancestry, “suggesting a role for genetic variation in contributing to DNA methylation differences in AA right colon,” the investigators said.

The work was supported the National Cancer Institute Cancer, the Case Comprehensive Cancer Center, and the University of Virginia Cancer Center. The authors and editorialists have disclosed no relevant financial relationships.

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

The Diagnosis: Anetoderma of Prematurity 

Anetoderma is a rare benign cutaneous disorder characterized by atrophic patches of skin due to dermal thinning. The term anetoderma is derived from the Greek words anetos (relaxed) and derma (skin).¹ The physical appearance of the skin is associated with a reduction or loss of elastic tissue in the dermal layer, as seen on histolopathology.²  

Two forms of anetoderma have been described. Primary anetoderma is an idiopathic form with no preceding inflammatory lesions. Secondary anetoderma is a reactive process linked to a known preceding inflammatory, infectious, autoimmune, or drug-induced condition.³ On histopathology, both primary and secondary anetoderma are characterized by a loss of elastic tissue or elastin fibers in the superficial to mid dermis.²  

Anetoderma of prematurity was first described in 1996 by Prizant et al⁴ in 9 extremely premature (24-29 weeks' gestation) infants in neonatal intensive care units (NICUs). Although the exact mechanism behind anetoderma of prematurity is still unknown, Prizant et al⁴ and other investigators⁵ postulated that application of adhesive monitoring leads in the NICU played a role in the development of the lesions. 

Iatrogenic anetoderma of prematurity is clinically characterized by circumscribed areas of either wrinkled macular depression or pouchlike herniations, ranging from flesh-colored to violaceous hues. Lesion size varies from a few millimeters to several centimeters in diameter, and they often are oval or round in shape.² Although not common, it is possible for the atrophic patches to be preceded by an area of ecchymosis without necrosis or atrophy and, if present, they usually evolve within a few days to the characteristic appearance of anetoderma.³ They are found at discrete sites where monitoring leads or other medical devices are commonly placed, such as the forehead, abdomen, chest, and proximal limbs. 

Lesions of anetoderma of prematurity are not present at birth, which distinguishes them from congenital anetoderma.⁶ It is unclear if the lesions are associated with the degree of prematurity, extremely low birth weight, or other associated factors of preterm birth. Although often clinically diagnosed, the diagnosis can be confirmed by a loss of elastic fibers on histopathology when stained with Verhoeff-van Gieson stain.¹ Over time, the atrophic patches have the potential to evolve into herniated forms of anetoderma. Self-healing or improvement of the lesions often does not occur. Although the lesion is benign, it often requires surgical correction later in life for cosmesis.  

Infants in the NICU are at risk for iatrogenic cutaneous injuries, which rarely may include anetoderma. Anetoderma of prematurity has been linked to the use of monitoring leads, adhesive tape, and other medical devices placed on the skin. Prizant et al⁴ postulated that the cause of anetoderma in these infants was irritants such as skin cleansers, urine, or sweat that may be trapped under the electrodes. Other hypotheses include local hypoxemia due to prolonged pressure from the electrodes on immature skin or excessive traction used when removing adhesive tape from the skin.^7,8 Premature infants may be more susceptible to these lesions because of the reduced epidermal thickness of premature skin; immaturity of skin structure; or functional immaturity of elastin deposition regulators, such as elastase, lysyl oxidase, the complement system, and decay-accelerating factor.³ The diagnosis should be differentiated from congenital anetoderma, which also has been described in premature neonates but is characterized by lesions that are present at birth. Its origins are still unclear, despite having histopathologic features similar to iatrogenic anetoderma.⁹  

Focal dermal hypoplasia (FDH) is the hallmark cutaneous finding in Goltz syndrome, a rare set of congenital abnormalities of the skin, oral structures, musculoskeletal system, and central nervous system. Similar to congenital anetoderma, FDH also is characterized by atrophic cutaneous lesions; however, the cutaneous lesions in FDH appear as linear, streaky atrophic lesions often with telangiectasias that follow Blaschko lines.¹⁰ The cutaneous lesions in FDH often are associated with other noncutaneous signs such as polydactyly or asymmetric limbs.¹⁰ Cutis laxa is caused by an abnormality in the elastic tissue resulting in a loose sagging appearance of the skin and frequently results in an aged facial appearance. There are both acquired and inherited forms that can be either solely cutaneous or present with extracutaneous features, such as cardiac abnormalities or emphysema.¹¹ 

In contrast to the atrophic appearance of anetodermas, connective tissue nevi and nevus lipomatosus superficialis present as hamartomas that either can be present at birth or arise in infancy. Connective tissue nevi are hamartomas of dermal connective tissue that consist of excessive production of collagen, elastin, or glycosaminoglycans and appear as slightly elevated, flesh-colored to yellow nodules or plaques.¹² Connective tissue nevi often are described in association with other diseases, most commonly tuberous sclerosis (shagreen patches) or familial cutaneous collagenoma. Nevus lipomatosus superficialis is an asymptomatic connective tissue hamartoma composed of mature adipocytes in the dermis. The lesions consist of clusters of flesh-colored to yellow, soft, rubbery papules or nodules with a smooth or verrucoid surface that do not cross the midline and may follow Blaschko lines.¹¹ 

With advances in neonatal infant medical care, survival of extremely premature infants is increasing, and it is possible that this rare cutaneous disorder may become more prevalent. Care should be taken to avoid unnecessary pressure on surfaces where electrodes are placed and tightly applied adhesive tape. When electrodes are placed on the ventral side, the child should be placed supine; similarly, place electrodes on the dorsal side when the child is lying prone.⁵ A diagnosis of anetoderma of prematurity later in childhood may be difficult, so knowledge and awareness can help guide pediatricians and dermatologists to a correct diagnosis and prevent unnecessary evaluations and/or concerns. 

The Diagnosis: Anetoderma of Prematurity 

Anetoderma is a rare benign cutaneous disorder characterized by atrophic patches of skin due to dermal thinning. The term anetoderma is derived from the Greek words anetos (relaxed) and derma (skin).¹ The physical appearance of the skin is associated with a reduction or loss of elastic tissue in the dermal layer, as seen on histolopathology.²  

Two forms of anetoderma have been described. Primary anetoderma is an idiopathic form with no preceding inflammatory lesions. Secondary anetoderma is a reactive process linked to a known preceding inflammatory, infectious, autoimmune, or drug-induced condition.³ On histopathology, both primary and secondary anetoderma are characterized by a loss of elastic tissue or elastin fibers in the superficial to mid dermis.²  

Anetoderma of prematurity was first described in 1996 by Prizant et al⁴ in 9 extremely premature (24-29 weeks' gestation) infants in neonatal intensive care units (NICUs). Although the exact mechanism behind anetoderma of prematurity is still unknown, Prizant et al⁴ and other investigators⁵ postulated that application of adhesive monitoring leads in the NICU played a role in the development of the lesions. 

Iatrogenic anetoderma of prematurity is clinically characterized by circumscribed areas of either wrinkled macular depression or pouchlike herniations, ranging from flesh-colored to violaceous hues. Lesion size varies from a few millimeters to several centimeters in diameter, and they often are oval or round in shape.² Although not common, it is possible for the atrophic patches to be preceded by an area of ecchymosis without necrosis or atrophy and, if present, they usually evolve within a few days to the characteristic appearance of anetoderma.³ They are found at discrete sites where monitoring leads or other medical devices are commonly placed, such as the forehead, abdomen, chest, and proximal limbs. 

Lesions of anetoderma of prematurity are not present at birth, which distinguishes them from congenital anetoderma.⁶ It is unclear if the lesions are associated with the degree of prematurity, extremely low birth weight, or other associated factors of preterm birth. Although often clinically diagnosed, the diagnosis can be confirmed by a loss of elastic fibers on histopathology when stained with Verhoeff-van Gieson stain.¹ Over time, the atrophic patches have the potential to evolve into herniated forms of anetoderma. Self-healing or improvement of the lesions often does not occur. Although the lesion is benign, it often requires surgical correction later in life for cosmesis.  

Infants in the NICU are at risk for iatrogenic cutaneous injuries, which rarely may include anetoderma. Anetoderma of prematurity has been linked to the use of monitoring leads, adhesive tape, and other medical devices placed on the skin. Prizant et al⁴ postulated that the cause of anetoderma in these infants was irritants such as skin cleansers, urine, or sweat that may be trapped under the electrodes. Other hypotheses include local hypoxemia due to prolonged pressure from the electrodes on immature skin or excessive traction used when removing adhesive tape from the skin.^7,8 Premature infants may be more susceptible to these lesions because of the reduced epidermal thickness of premature skin; immaturity of skin structure; or functional immaturity of elastin deposition regulators, such as elastase, lysyl oxidase, the complement system, and decay-accelerating factor.³ The diagnosis should be differentiated from congenital anetoderma, which also has been described in premature neonates but is characterized by lesions that are present at birth. Its origins are still unclear, despite having histopathologic features similar to iatrogenic anetoderma.⁹  

Focal dermal hypoplasia (FDH) is the hallmark cutaneous finding in Goltz syndrome, a rare set of congenital abnormalities of the skin, oral structures, musculoskeletal system, and central nervous system. Similar to congenital anetoderma, FDH also is characterized by atrophic cutaneous lesions; however, the cutaneous lesions in FDH appear as linear, streaky atrophic lesions often with telangiectasias that follow Blaschko lines.¹⁰ The cutaneous lesions in FDH often are associated with other noncutaneous signs such as polydactyly or asymmetric limbs.¹⁰ Cutis laxa is caused by an abnormality in the elastic tissue resulting in a loose sagging appearance of the skin and frequently results in an aged facial appearance. There are both acquired and inherited forms that can be either solely cutaneous or present with extracutaneous features, such as cardiac abnormalities or emphysema.¹¹ 

In contrast to the atrophic appearance of anetodermas, connective tissue nevi and nevus lipomatosus superficialis present as hamartomas that either can be present at birth or arise in infancy. Connective tissue nevi are hamartomas of dermal connective tissue that consist of excessive production of collagen, elastin, or glycosaminoglycans and appear as slightly elevated, flesh-colored to yellow nodules or plaques.¹² Connective tissue nevi often are described in association with other diseases, most commonly tuberous sclerosis (shagreen patches) or familial cutaneous collagenoma. Nevus lipomatosus superficialis is an asymptomatic connective tissue hamartoma composed of mature adipocytes in the dermis. The lesions consist of clusters of flesh-colored to yellow, soft, rubbery papules or nodules with a smooth or verrucoid surface that do not cross the midline and may follow Blaschko lines.¹¹ 

With advances in neonatal infant medical care, survival of extremely premature infants is increasing, and it is possible that this rare cutaneous disorder may become more prevalent. Care should be taken to avoid unnecessary pressure on surfaces where electrodes are placed and tightly applied adhesive tape. When electrodes are placed on the ventral side, the child should be placed supine; similarly, place electrodes on the dorsal side when the child is lying prone.⁵ A diagnosis of anetoderma of prematurity later in childhood may be difficult, so knowledge and awareness can help guide pediatricians and dermatologists to a correct diagnosis and prevent unnecessary evaluations and/or concerns. 

The Diagnosis: Anetoderma of Prematurity 

Anetoderma is a rare benign cutaneous disorder characterized by atrophic patches of skin due to dermal thinning. The term anetoderma is derived from the Greek words anetos (relaxed) and derma (skin).¹ The physical appearance of the skin is associated with a reduction or loss of elastic tissue in the dermal layer, as seen on histolopathology.²  

Two forms of anetoderma have been described. Primary anetoderma is an idiopathic form with no preceding inflammatory lesions. Secondary anetoderma is a reactive process linked to a known preceding inflammatory, infectious, autoimmune, or drug-induced condition.³ On histopathology, both primary and secondary anetoderma are characterized by a loss of elastic tissue or elastin fibers in the superficial to mid dermis.²  

Anetoderma of prematurity was first described in 1996 by Prizant et al⁴ in 9 extremely premature (24-29 weeks' gestation) infants in neonatal intensive care units (NICUs). Although the exact mechanism behind anetoderma of prematurity is still unknown, Prizant et al⁴ and other investigators⁵ postulated that application of adhesive monitoring leads in the NICU played a role in the development of the lesions. 

Iatrogenic anetoderma of prematurity is clinically characterized by circumscribed areas of either wrinkled macular depression or pouchlike herniations, ranging from flesh-colored to violaceous hues. Lesion size varies from a few millimeters to several centimeters in diameter, and they often are oval or round in shape.² Although not common, it is possible for the atrophic patches to be preceded by an area of ecchymosis without necrosis or atrophy and, if present, they usually evolve within a few days to the characteristic appearance of anetoderma.³ They are found at discrete sites where monitoring leads or other medical devices are commonly placed, such as the forehead, abdomen, chest, and proximal limbs. 

Lesions of anetoderma of prematurity are not present at birth, which distinguishes them from congenital anetoderma.⁶ It is unclear if the lesions are associated with the degree of prematurity, extremely low birth weight, or other associated factors of preterm birth. Although often clinically diagnosed, the diagnosis can be confirmed by a loss of elastic fibers on histopathology when stained with Verhoeff-van Gieson stain.¹ Over time, the atrophic patches have the potential to evolve into herniated forms of anetoderma. Self-healing or improvement of the lesions often does not occur. Although the lesion is benign, it often requires surgical correction later in life for cosmesis.  

Infants in the NICU are at risk for iatrogenic cutaneous injuries, which rarely may include anetoderma. Anetoderma of prematurity has been linked to the use of monitoring leads, adhesive tape, and other medical devices placed on the skin. Prizant et al⁴ postulated that the cause of anetoderma in these infants was irritants such as skin cleansers, urine, or sweat that may be trapped under the electrodes. Other hypotheses include local hypoxemia due to prolonged pressure from the electrodes on immature skin or excessive traction used when removing adhesive tape from the skin.^7,8 Premature infants may be more susceptible to these lesions because of the reduced epidermal thickness of premature skin; immaturity of skin structure; or functional immaturity of elastin deposition regulators, such as elastase, lysyl oxidase, the complement system, and decay-accelerating factor.³ The diagnosis should be differentiated from congenital anetoderma, which also has been described in premature neonates but is characterized by lesions that are present at birth. Its origins are still unclear, despite having histopathologic features similar to iatrogenic anetoderma.⁹  

Focal dermal hypoplasia (FDH) is the hallmark cutaneous finding in Goltz syndrome, a rare set of congenital abnormalities of the skin, oral structures, musculoskeletal system, and central nervous system. Similar to congenital anetoderma, FDH also is characterized by atrophic cutaneous lesions; however, the cutaneous lesions in FDH appear as linear, streaky atrophic lesions often with telangiectasias that follow Blaschko lines.¹⁰ The cutaneous lesions in FDH often are associated with other noncutaneous signs such as polydactyly or asymmetric limbs.¹⁰ Cutis laxa is caused by an abnormality in the elastic tissue resulting in a loose sagging appearance of the skin and frequently results in an aged facial appearance. There are both acquired and inherited forms that can be either solely cutaneous or present with extracutaneous features, such as cardiac abnormalities or emphysema.¹¹ 

In contrast to the atrophic appearance of anetodermas, connective tissue nevi and nevus lipomatosus superficialis present as hamartomas that either can be present at birth or arise in infancy. Connective tissue nevi are hamartomas of dermal connective tissue that consist of excessive production of collagen, elastin, or glycosaminoglycans and appear as slightly elevated, flesh-colored to yellow nodules or plaques.¹² Connective tissue nevi often are described in association with other diseases, most commonly tuberous sclerosis (shagreen patches) or familial cutaneous collagenoma. Nevus lipomatosus superficialis is an asymptomatic connective tissue hamartoma composed of mature adipocytes in the dermis. The lesions consist of clusters of flesh-colored to yellow, soft, rubbery papules or nodules with a smooth or verrucoid surface that do not cross the midline and may follow Blaschko lines.¹¹ 

With advances in neonatal infant medical care, survival of extremely premature infants is increasing, and it is possible that this rare cutaneous disorder may become more prevalent. Care should be taken to avoid unnecessary pressure on surfaces where electrodes are placed and tightly applied adhesive tape. When electrodes are placed on the ventral side, the child should be placed supine; similarly, place electrodes on the dorsal side when the child is lying prone.⁵ A diagnosis of anetoderma of prematurity later in childhood may be difficult, so knowledge and awareness can help guide pediatricians and dermatologists to a correct diagnosis and prevent unnecessary evaluations and/or concerns. 

Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.

“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.

But those statistics have not been available from a robust population-based source.

Now, there is hope that they will – at last – be collected.

A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.

But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.

“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.

“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.

But this database has never included information on cancer recurrence.

In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
 

New project

The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.

The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.

She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.

“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
 

Why the change now?

“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.

Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.

Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.

In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
 

Tracking recurrences

In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.

Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.

“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.

To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.

On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.

Nonetheless, these clinical trials provide a starting place.

The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.

The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.

“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.

The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.

The study was supported by NCI.

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

Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.

“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.

But those statistics have not been available from a robust population-based source.

Now, there is hope that they will – at last – be collected.

A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.

But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.

“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.

“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.

But this database has never included information on cancer recurrence.

In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
 

New project

The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.

The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.

She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.

“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
 

Why the change now?

“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.

Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.

Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.

In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
 

Tracking recurrences

In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.

Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.

“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.

To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.

On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.

Nonetheless, these clinical trials provide a starting place.

The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.

The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.

“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.

The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.

The study was supported by NCI.

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

Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.

“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.

But those statistics have not been available from a robust population-based source.

Now, there is hope that they will – at last – be collected.

A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.

But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.

“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.

“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.

But this database has never included information on cancer recurrence.

In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
 

New project

The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.

The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.

She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.

“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
 

Why the change now?

“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.

Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.

Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.

In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
 

Tracking recurrences

In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.

Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.

“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.

To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.

On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.

Nonetheless, these clinical trials provide a starting place.

The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.

The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.

“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.

The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.

The study was supported by NCI.

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

The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia –  call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out. 

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
 

Steepest changes in adenocarcinomas in younger groups

In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.

A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.

The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.

The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).

There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.

Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.

The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”

They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
 

Calls for next steps

The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.

They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.  

“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.

This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested.  “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.

“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.

The study authors concluded somewhat differently.

“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.

They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”

Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.

This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”

The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.

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

The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia –  call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out. 

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
 

Steepest changes in adenocarcinomas in younger groups

In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.

A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.

The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.

The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).

There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.

Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.

The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”

They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
 

Calls for next steps

The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.

They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.  

“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.

This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested.  “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.

“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.

The study authors concluded somewhat differently.

“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.

They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”

Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.

This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”

The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.

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

The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia –  call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out. 

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
 

Steepest changes in adenocarcinomas in younger groups

In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.

A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.

The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.

The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).

There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.

Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.

The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”

They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
 

Calls for next steps

The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.

They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.  

“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.

This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested.  “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.

“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.

The study authors concluded somewhat differently.

“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.

They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”

Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.

This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”

The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.

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

The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia –  call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out. 

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
 

Steepest changes in adenocarcinomas in younger groups

In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.

A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.

The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.

The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).

There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.

Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.

The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”

They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
 

Calls for next steps

The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.

They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.  

“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.

This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested.  “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.

“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.

The study authors concluded somewhat differently.

“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.

They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”

Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.

This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”

The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC. 

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

The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia –  call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out. 

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
 

Steepest changes in adenocarcinomas in younger groups

In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.

A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.

The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.

The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).

There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.

Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.

The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”

They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
 

Calls for next steps

The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.

They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.  

“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.

This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested.  “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.

“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.

The study authors concluded somewhat differently.

“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.

They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”

Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.

This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”

The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC. 

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

The risk for colorectal cancer (CRC) in young adults is actually lower than has been estimated, because previous studies did not differentiate between colorectal adenocarcinoma and the histologically different carcinoid tumors, which are incidental findings, say experts.

New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.

They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.

Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.

However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).

But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.

The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”

The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.

These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”

This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.

This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.

The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia –  call for action based on the new findings.

“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.

They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”

However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.

Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.

“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”

“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out. 

“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.

Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.

Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
 

Steepest changes in adenocarcinomas in younger groups

In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.

A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.

The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.

The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).

There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.

Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.

The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”

They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
 

Calls for next steps

The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.

They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.  

“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.

This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested.  “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.

“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.

The study authors concluded somewhat differently.

“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.

They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”

Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.

This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”

The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC. 

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