Shifting trends in CRC demographics, severity prove you are ‘not too young to have cancer’
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Despite a decline in the overall incidence of colorectal cancer in the U.S., recent population-based data from the American Cancer Society show an alarming shift to younger age and more advanced disease at diagnosis.
“Although there is still progress in reducing incidence and mortality overall, if you pull up the hood, it becomes apparent that there are very concerning patterns in terms of the rapid shift to a younger patient population,” Rebecca Siegel, MPH, epidemiologist and senior scientific director of surveillance research at the American Cancer Society, told Healio Gastroenterology. “Those younger patients have unique needs compared to patients in their 70s, which was the more typical patient 20 to 30 years ago. Not only are we seeing younger patients, but also more advanced disease.”
Source: Folasade P. May, MD, PhD, MPhil
In CA: A Cancer Journal for Clinicians, Siegel and colleagues reported a slowing decline in overall annual incidence from 3% to 4% in the 2000s to 1% in the following decade, with an increase in the proportion of cases among those younger than 55 years from 11% in 1995 to 20% in 2019.
Further, 60% of all new cases of CRC were diagnosed at advanced stages in 2019 compared with 52% in the mid-2000s and 57% in 1995. There also was a shift from right-sided tumors to left-sided tumors and rectal cancer.
Coupled with preceding research from George J. Chang, MD, MS, FACS, FASCRS, FSSO, and colleagues in JAMA Surgery, which estimated 2030 incidence rates for colon and rectal cancer will increase by 90% and 124.2%, respectively, among patients aged 20 to 34 years and by 27.7% and 46% among patients aged 35 to 49 years, experts agreed CRC is no longer a disease of older adults.
“Historically, people have considered colorectal cancer to be a disease of older people, so younger people may have symptoms that go ignored or are inadequately evaluated. Also, younger people often shy away from talking about their bowel functions and, therefore, can delay getting medical attention,” Chang, professor and chair ad interim in the department of colon and rectal surgery at the University of Texas MD Anderson Cancer Center, said. “You are not too young to have cancer. For society as a whole, it is important to be raising awareness and promoting evaluation.”
Healio Gastroenterology spoke with experts across the field to understand the shifts in CRC trends, the implications for patient care, and barriers that persist in screening and linkage to care.
A Shift in Demographics
While the answer is largely unknown to the question of why trends in incidence rates, disease severity and tumor location have shifted over time, Folasade P. May, MD, PhD, MPhil, associate professor of medicine and director of the Melvin and Bren Simon Gastroenterology Quality Improvement Program at the University of California, Los Angeles, hypothesized that environmental factors may play the largest role.
“We know it is environmental and not genetic because it happened too fast,” she said. “We [the research community] think it is probably a combination of what we are putting in our bodies and potentially the way we live our life in high-income countries. There are also data to support the role of diet, obesity and diabetes as well as environmental toxins and plastics.”
Chang added that additional lifestyle factors such as being sedentary, consuming too many processed foods and not enough fruits and vegetables, and excessive alcohol use may also contribute to increased risk for CRC.
“What came first is not entirely clear,” he said. “You can have the healthiest, fiber-rich diet and still get colorectal cancer. We do not have a perfect causal agent to point to.”
Caitlin C. Murphy, PhD, MPH, associate professor at UTHealth Houston School of Public Health, noted that emerging evidence also has suggested that events and life exposures as early as the prenatal period may explain some of these rising incidence trends.
“Many of the risk factors we have long thought to be related to colorectal cancer may play only a small part in the epidemic. Rather, risk factors and the things that we never once thought were possible to be associated with colorectal cancer seem to be playing a really important role,” Murphy previously told Healio Gastroenterology. “The reasons a patient may have colorectal cancer today are different than the reasons many years ago. We need to think outside the box and start to identify other risk factors that may explain increasing rates.”
Early Screening, Care Strategies
Based on empirical evidence, the American Cancer Society conducted microsimulation model analyses in 2018 to evaluate the benefits and risks of CRC screening at different ages. Results led to the recommendation that the screening age be lowered from 50 to 45 years among patients at average risk for CRC. The U.S. Preventive Services Task Force adopted the same guidance in their 2021 recommendation update.
Siegel and colleagues have since reported that screening average-risk individuals aged 45 to 49 years has only had a “modest impact” on colonoscopy volume, with data from the National Health Interview Survey showing that screening uptake remains low among patients aged 45 to 49 years compared with those aged 50 to 54 years (20% vs. 50%).
“I think there is a tendency to believe that if we change the guidelines people will do what the guideline says,” Murphy said. “Any behavioral scientists will tell you that is not true, and we may need unique ways to engage this population and this age group to really help them engage in screening.”
Of 153,020 estimated new cases of CRC in the U.S. in 2023, 13% will be among patients younger than 50 years, with approximately 43% of these patients aged 45 to 49 years, Siegel and colleagues noted.
Seth A. Gross, MD, FACG, FASGE, AGAF, professor of medicine and clinical chief in the division of gastroenterology and hepatology at NYU Langone Health, advised younger patients not to ignore symptoms.
“If they notice rectal bleeding, abdominal pain or change in bowel habits, these are clues that they should speak with their physician about the significance of these changes and should undergo colorectal cancer screening or at least a further workup of these symptoms,” he said.
Chang added that another determinant of risk for CRC is hereditary predisposition: “Those with known hereditary colorectal cancer syndromes, those with a first-degree relative with colorectal cancer are also at increased risk. We generally recommend that first-degree relatives are screened 10 years younger than the age at which their family member was diagnosed; if you are 50 when you are diagnosed with colorectal cancer, your siblings or children should have their first screening at 40. Particularly in younger people, we want to make sure we do genetic testing.”
Coming to a decision about the appropriate time to begin screening is a “very individualized approach,” Siegel noted.
Patients may also opt for less invasive strategies such as fecal immunochemical tests (FIT), multitarget stool DNA tests, stool guaiac tests, or sigmoidoscopy alone or combined with FIT. The most invasive screening option is colonoscopy, which is required for diagnosis following a positive result from any noninvasive testing approach.
“The gold standard test has been colonoscopy because you have the ability to look through the entire colon to identify and remove polyps,” Gross said. “But at the end of the day, messaging is that the best colorectal cancer test is the one that the person will do.”
‘A Different Place in Life’
In contrast to the decreasing incidence of CRC that the American Cancer Society has reported among older adults, rates among those aged 20 to 39 years have increased since the mid-1980s and among patients aged 40 to 45 years since the mid-1990s. From 2011 through 2019, Siegel and colleagues observed rates increased by 1.9% per year among those younger than 50 years as well as those aged 50 to 54 years.
Further, early-onset patients were more often diagnosed with advanced disease with rates increasing by approximately 3% per year for regional-stage and distant-stage disease compared with a decline of 1% per year for localized-stage disease from 2010 to 2019.
“Another issue with young patients is that they are in a different place in life,” Siegel said. “It used to be that most colorectal cancer patients were in their 70s and those people usually are not working and also are not concerned about fertility. Younger patients are very worried about preserving their fertility and those conversations often are not occurring until it is too late.”
She continued: “Having an appreciation for the unique needs of younger patients vs. older patients can really go far in informing physicians how to serve these patients more effectively.”
CRC is unique in that the goal is not only early detection but also prevention, Chang explained.
“We want to detect it at the earliest stage and that is important because the earlier the stage, the more curable it is and the less treatment that the patient requires; therefore, less toxicity and better quality of life,” he said. “But if through screening we can detect a polyp before it ever turns into a cancer, then we can prevent the development of colorectal cancer in the first place. The young population is uniquely more sensitive to this challenge for early detection and prevention, which I think is a big hurdle.”
Racial, Ethnic Disparities
CRC incidence, survival and mortality “vary substantially” by race, Siegel and colleagues reported, with the highest rates observed among American Indian and Alaskan Native (AIAN) patients as well as non-Hispanic Black patients. Compared with white men, mortality rates are 46% higher among AIAN men and 44% higher among Black men.
“It is not just the Black population,” Siegel said. “Another very important population is Native American people, especially those in Alaska. In terms of screening, rates for the native population are relatively low and only about half of the Native American people are current for screening.”
In a 2022 American Cancer Society report, Tyler B. Kratzer, MPH, and colleagues reported that from 1998 to 2018, CRC rates in people younger than 50 years increased by approximately 79% in AIAN individuals outside of Alaska (from 9.9 to 17.7 cases per 100,000) and by 85% among Alaska native individuals (from 18.8 to 34.8 cases per 100,000) compared with 33% among white individuals (from 9.4 to 12.5 cases per 100,000). Mortality rates among those younger than 50 years increased by 3% annually among AIAN patients vs. 1.8% among white patients from 2010 through 2019.
“The very structures that we have used to build U.S. society have, unfortunately, ingrained barriers to health,” May said. “For example, if we talk about how neighborhoods are structured, the reality is that most people of color live in neighborhoods that are near freeways, which are intolerable for exercise, or are in food deserts where individuals do not have access to healthy food.
“Whether you are talking about immigrant populations, Latino populations, Black populations or American Indian populations, the root of disparities is in the social determinants of health that are often a result of structural or systemic racism.”
To counter inequities seen in screening and linkage to care, Siegel emphasizes awareness: “There is a perception that equal access means equal treatment, and that is not the case. Physicians need to realize that we all have unconscious biases that are operating on a daily basis and being aware of that is the first step.”
In a previous interview with Healio Gastroenterology,Pegah Hosseini-Carroll, MD, associate professor of medicine and program director for GI fellowship at the University of Mississippi Medical Center and member of the ASGE Diversity, Equity and Inclusion subcommittee, said the key to mitigating disparities in screening and care include improving culturally competent care, increasing the number of minority care providers in the workforce and having educational materials targeted to the appropriate patient literacy level.
“On a more systemic level, increasing access to health care and expanding insurance are vital to decreasing colon cancer screening disparities,” she said.
Mediating Additional Barriers to Care
When it comes to additional barriers to care, May told Healio Gastroenterology she likes to break them down by the patient, provider, health system and policy level.
“Some patients just do not have a doctor or they never see their doctor,” she said. “Some patients want to get a colonoscopy, but they can’t schedule it because the only times offered are Monday through Friday from 9 to 5.”
Beyond patient factors, May noted the difficulty with providers is that some do not even recommend screening. And from a health system level, many institutions either do not have the infrastructure to support integrated care or offer electronic health record alerts.
“A lot of it has to do with the health care system,” she said. “We need to do a better job of capturing data on who is screened and going after all of the patients who are unscreened, even if that means using tools like telephone calls, reminders, mailed FIT kits or even patient navigation.”
She added, “There also needs to be separate efforts in populations that are not in health systems to bring care to their door. It all relies on different strategies for the health care connected vs. the unconnected.”
From a policy level, strides have been made through CMS and Medicare to expand coverage over the past year, including the 2023 Medicare Physician Fee Schedule, lowered minimum coverage age and follow-up colonoscopy covered under the KX modifier.
“In terms of how these decisions will impact disparities, it will be incremental in the coming years. But of course, increasing access is always what we want so this should certainly remove some barriers,” Siegel said. “Once we increase insurance rates so that everyone has access to health insurance, that is not the end of the road. We have to ensure that everyone has access to high-quality screening as well as high-quality follow-up care and treatment.”
Expanding CRC Screening Options
With an overarching goal of making screening easier and widely accessible to the general public, ongoing studies continue to investigate the diagnostic accuracy and longitudinal performance of novel screening modalities that have the potential to “disrupt the CRC screening landscape,” Aasma Shaukat, MD, MPH, and Theodore R. Levin, MD, wrote in Nature Reviews Gastroenterology & Hepatology.
“In the U.S., only 67% of patients are up to date with CRC screening, as reported in 2021. Although colonoscopy is highly sensitive and specific for CRC detection and polyp removal, it is invasive, expensive and resource intensive,” they wrote. “Hence, there is an unfulfilled need for multiple-modality CRC screening that can improve current CRC screening rates.
“Newer technologies might be resource-effective strategies when used to select patients for colonoscopy.”
Included in development are blood-based tests that must meet approval thresholds outlined by CMS in 2021 as having 90% specificity and 74% sensitivity for CRC compared with an accepted standard, as well as approval from the FDA and endorsement from at least one professional society.
They noted several studies are underway for blood-based screening modalities, including:
the PREEMPT CRC trial from Freenome, which is investigating the ability of cell-free DNA with artificial intelligence to detect CRC and advanced adenomas;
the ECLIPSE trial from Guardant, which is investigating the circulating tumor DNA LUNAR test designed to detect cell-free tumor DNA;
a primary case-control study from CancerSeek investigating a multicancer detection test that detects circulating proteins and mutations; and
the GRAIL test, which is a multicancer early-detection test.
Additional image-based modalities under investigation are the CT capsule, a novel X-ray imaging capsule that emits low-dose X-ray beams as it travels through the colon, and MRI colonography, a newly developed, noninvasive method that evaluates extracolonic findings and cancer metastases.
“Before we see any additional changes to the screening age, we will probably see a lot more advances in noninvasive testing; that is the holy grail to higher rates of screening,” Chang said. “Maybe the future is blood-based testing. People do not seem to mind having their blood drawn, while stool and bowel issues are still such a taboo topic.” He continued: “The bottom line is, as we get to less invasive testing, that test needs to be just as good at detecting precancerous lesions as it is at detecting cancers.”
Best Practices for Screening, Treating Patients
With these shifting trends in mind, Gross said the key to screening and treating patients now is through awareness across specialties and providers.
“We need to make sure we do a good job raising awareness,” he said. “Not just among the gastroenterologists who perform screening, but working with the primary care physicians, internal medicine doctors — whoever a patient’s touchpoint is to make sure they know their screening eligibility.”
Gross continued: “The one thing that we know about colorectal cancer is that if it is caught early, it is treatable and beatable and, of course, if you follow screening recommendations, it is preventable.”
According to May, we are at a “change in the landscape of colorectal cancer” that will require a shift in how providers practice medicine and how we as a society spread awareness about CRC.
“It is also a huge call for a lifestyle revolution in our country,” she said. “We need to be aware of the things that we are doing that are not healthy for ourselves and for the human genome. We need to clean up our diets, make sure that we are living highly mobile and maintaining a healthy weight.”
- References:
- Center for Medicare & Medicaid Services, MLN Matters: “Removal of a National Coverage Determination & Expansion of Coverage of Colorectal Cancer Screening,” MM13017 Revised. Accessed: Feb 28, 2023.
- Chang GJ, et al. JAMA Surg. 2015;doi:10.1001/jamasurg.2014.1756.
- CMS. Calendar year 2023 Medicare physician fee schedule final rule. www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2023-medicare-physician-fee-schedule-final-rule. Accessed: March 29, 2023.
- Kratzer TB, et al. CA Cancer J Clin. 2022;doi:10.3322/caac.21757.
- Murphy CC, et al. JNCI Cancer Spectr. 2023;doi:10.1093/jncics/pkad021.
- Shaukat A, et al. Nat Rev Gastroenterol Hepatol. 2022;doi:10.1038/s41575-022-00612-y.
- Siegel RL, et al. CA Cancer J Clin. 2023;doi:10.3322/caac.21772.
- Sinicrope FA. N Engl J Med. 2022;doi:10.1056/NEJMra2200869.
- Wolf A, et al. CA Cancer J Clin. 2018;doi:10.3322/caac.21457.
- For more information:
- George J. Chang, MD, MS, FACS, FASCRS, FSSO, is a professor and chair ad interim in the department of colon and rectal surgery at the University of Texas MD Anderson Cancer Center and can be reached at gchang@mdanderson.org.
- Seth A. Gross, MD, FACG, FASGE, AGAF, is a professor of medicine and clinical chief in the division of gastroenterology and hepatology at NYU Langone Health and can be reached at seth.gross@nyulangone.org.
- Folasade P. May, MD, PhD, MPhil, is an associate professor of medicine and director of the Melvin and Bren Simon Gastroenterology Quality Improvement Program at the University of California, Los Angeles, and can be reached at fmay@mednet.ucla.edu.
- Caitlin C. Murphy, PhD, MPH, is an associate professor at UTHealth Houston School of Public Health and can be reach at caitlin.c.murphy@uth.tmc.edu.
- Rebecca Siegel, MPH, is an epidemiologist and the senior scientific director of surveillance research at the American Cancer Society and can be reached at rebecca.siegel@cancer.org.
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