Beyond Colonoscopy: Shifting Incidence, Mortality Prompts New Era of Colorectal Cancer Screening

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The recent rise in colorectal cancer incidence and mortality in younger patients has sparked a serious discussion about strategies to increase screening uptake and adherence, raising questions about the role of noninvasive tests versus the traditional “gold standard,” colonoscopy.

From left to right: Christina Wu, MD; Ahmedin Jemal, DVM, PhD; Adelina Hung, MD | Credit: Mayo Clinic; American Cancer Society; Sinai Health System

From left to right: Christina Wu, MD; Ahmedin Jemal, DVM, PhD; Adelina Hung, MD

Credit: Mayo Clinic; American Cancer Society; Sinai Health System

Two decades ago, colorectal cancer was the fourth leading cause of cancer-related death in both men and women under 50 years of age – now, it has jumped to the leading cause in men and the second most common cause in women, behind breast cancer.1

A common misconception about colorectal cancer is that it only affects older adults. Although it is most frequently diagnosed in people over 65 years of age, incidence in this group is on the decline. Now, younger patients often thought to be safe from colorectal cancer are quickly becoming its prime victim – people younger than 50 years of age are more likely to be diagnosed with advanced disease than their older counterparts.2

“The hot topic in colorectal cancer has been the increase in incidence and mortality rates in patients below the age of 55,” Ahmedin Jemal, DVM, PhD, senior vice president of the surveillance and health equity science department of the American Cancer Society, explained in an interview with HCPLive.

Colorectal Cancer Striking Young

Indeed, from 2011-2019, overall colorectal cancer rates decreased by about 1% per year, although this declining incidence was confined to individuals 65 years of age and older; rates have increased by 1-2% per year since the mid-1990s in those younger than 55 years of age. Similarly, overall colorectal cancer mortality rates have dropped by 56% since 1970, but again, this progress is confined to older adults; mortality rates in individuals under 55 years of age have increased by about 1% per year since the mid-2000s.1

In 2021, the US Preventive Services Task Force (USPSTF) sought to address these shifting trends and the rising incidence in younger patient populations by lowering the recommended screening age from 50 years to 45 years.3

“That has been helpful in catching more young people and preventing colon cancer in that population” Adelina Hung, MD, clinical assistant professor at Rosalind Franklin University of Medicine and Science and gastroenterologist at Sinai Health System Chicago, explained in an interview with HCPLive. Later, Hung also emphasized the importance of considering patients younger than 45 years of age and urging them to monitor their GI symptoms. “Most people will say ‘Oh, that's hemorrhoids, or that’s irritable bowel syndrome, because you're too young, you're in your 20s or 30s’, but now we are seeing that if younger patients are having these symptoms persistently, they should go ahead and get a colonoscopy and see a gastroenterologist.”

Reducing Risk with Lifestyle Changes, Screening Adherence

Although experts do not know exactly what is causing the uptick among younger patients, it is assumed to be multifactorial, likely attributed to a mix of hereditary, environmental, and lifestyle factors. Accordingly, Hung suggests “anything that the younger population can do to lead a healthy lifestyle will be helpful, like exercising, eating more fibrous food, decreasing processed food, not smoking, not drinking, and making sure they know their family history very well.”

Along with these lifestyle choices, the US Centers for Disease Control and Prevention cites routine screening as the most effective way to reduce the risk of colorectal cancer. Almost all colorectal cancers begin as precancerous polyps in the colon or rectum and can be present for years before invasive cancer develops. Screening can identify and allow for the removal of these polyps before they turn into cancer, or detect cancer in its early stages when it’s easiest to treat. However, as of 2021, only 59% of adults 45 years of age and older were up to date with screenings, and screening was lowest among adults 45-49 and 50-54 years of age (20% and 50%, respectively).4,5

“If we can increase colorectal cancer screening uptake in that group, we can combat the incidence and mortality rates,” Jemal said.

The Value of Colonoscopy

Traditionally, colonoscopy is considered the “gold standard” due to its efficacy for both prevention and screening, allowing doctors to look for growths, other abnormal tissue, or cancer in the rectum/colon and remove any abnormalities they may find during the same procedure.6

“Colonoscopy is the only sort of diagnostic procedure that also can prevent cancer because if they pick up polyps, they're going to prevent those polyps from eventually becoming cancer,” Christina Wu, MD, professor in the department of internal medicine in the division of hematology/oncology and oncologist at Mayo Clinic, explained in an interview with HCPLive.

However, the effectiveness of colonoscopy recently came under fire with results from the Nordic-European Initiative on Colorectal Cancer (NordICC) trial, the first published randomized clinical trial testing its efficacy for colorectal cancer screening. The pragmatic, randomized trial enrolled presumptively healthy men and women 55 - 64 years of age drawn from Poland, Norway, Sweden, and the Netherlands who were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy or to receive no invitation or screening.7

Although individuals in the screening invitation group had a lower risk of colorectal cancer at 10 years compared to the usual-care group (0.98% vs 1.20%; Risk ratio, 0.82; 95% CI, 0.70–0.93), there was no statistically significant difference in colorectal cancer–specific death (0.28% vs 0.31%) or all-cause mortality (11.03% vs 11.04%) between the groups. However, many have pointed out several important limitations to these findings, including the 47% screening rate among participants randomly assigned to the screening invitation group.7,8

“I think we can learn that you may not be able to only ask once. With our patients, we really should be encouraging and making sure that we are talking to them about it, and not just once and giving up,” Wu explained. “I do think we still walk away thinking that there is benefit with colonoscopies.”

Addressing Barriers to Access

Although it is the gold standard for screening, barriers to access prevent many patients from seeking a colonoscopy: “If we think about the fact that often these procedures are done on weekdays, Monday through Friday, that's when people are working, whether they're going to be able to or want to take a day off to do this specifically, and they also have to be fasting and doing the prep the day before even, and then they need a ride, because often that's given with sedation,” Wu said, describing it as a “big burden” to ask of patients.

Beyond colonoscopy, the FDA has cleared or approved several other screening procedures for detecting colorectal cancer. Available stool-based tests include fecal immunochemical testing (FIT) and multitarget stool DNA testing (Cologuard, Exact Sciences), while other visual screening options include flexible sigmoidoscopy and CT colonography.6,9

Several new screening modalities are also in development for colorectal cancer. Although the FDA approved the first blood-based colorectal cancer screening test in 2016 with Epi proColon and several others are in various stages of evaluation, a recent study found that even a blood test meeting Centers for Medicare and Medicaid Services coverage criteria for sensitivity of ≥ 74% and specificity of ≥ 90% would lead to greater costs and worse outcomes versus FIT, sDNA-FIT, and colonoscopy.10,11

Accordingly, the American Gastroenterological Association emphasizes blood tests are merely an additional tool to help identify colorectal cancer early, and they are not interchangeable with colonoscopy for colorectal cancer screening.12 Similarly, although many non-invasive alternatives may increase participation for patients hesitant or unable to get a colonoscopy, if the result is positive or abnormal on some of these tests, a colonoscopy will still ultimately be required to complete the screening process. Additionally, depending on the test, most noninvasive options must be done more frequently than colonoscopy, creating more opportunities for nonadherence among patients.6,13

Despite the aforementioned barriers to colonoscopy and many patients’ hesitancy toward the procedure, Hung described positive feedback from her patients, saying most people “don't realize how easy it is” and that in her experience, many patients say the hardest part was the preparation leading up to the procedure.

“We have so few tools in medicine to prevent cancer, so when those tools are available, they need to be utilized better. It's so unfortunate because we have a really good tool to prevent colon cancer, we just need people to get it done,” said Hung, who noted that despite colonoscopies being the best screening method, “It’s still better to do something than nothing, and that’s why it’s so important to have this month.”

References:

  1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. American Cancer Society. https://doi.org/10.3322/caac.21820
  2. Katella K. Colorectal Cancer: What Millennials and Gen Zers Need to Know. Yale Medicine. January 17, 2024. Accessed March 21, 2024. https://www.yalemedicine.org/news/colorectal-cancer-in-young-people
  3. US Preventive Services Task Force. Colorectal Cancer: Screening. Recommendation Topics. May 18, 2021. Accessed March 21, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening
  4. US Centers for Disease Control and Prevention. What Can I Do to Reduce My Risk of Colorectal Cancer? Colorectal Cancer. February 23, 2023. Accessed March 21, 2024. https://www.cdc.gov/cancer/colorectal/basic_info/prevention.htm
  5. National Colorectal Cancer Roundtable. 80% in Every Community. American Cancer Society. Accessed March 22, 2024. https://nccrt.org/our-impact/80-in-every-community/
  6. US Centers for Disease Control and Prevention. Colorectal Cancer Screening Tests. Colorectal Cancer. February 23, 2023. Accessed March 21, 2024. https://www.cdc.gov/cancer/colorectal/basic_info/screening/tests.htm
  7. Bretthauer M, Løberg M, Wieszczy P, et al. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. N Engl J Med. doi:10.1056/NEJMoa2208375
  8. Surana R, Ng K. The NordICC Trial: The Devil Is in the Details. The ASCO Post. November 2, 2022. Accessed March 22, 2024. https://ascopost.com/news/november-2022/the-nordicc-trial-the-devil-is-in-the-details/
  9. Shaukat A, Levin TR. Current and future colorectal cancer screening strategies. Nat Rev Gastroenterol Hepatol. 2022;19(8):521-531. doi:10.1038/s41575-022-00612-y
  10. Colorectal Cancer Alliance. Colon Health Alert: FDA Approves New Screening Test Epi proColon. April 19, 2016. Accessed March 26, 2024. https://colorectalcancer.org/article/colon-health-alert-fda-approves-new-screening-test-epi-procolon
  11. Brooks A. Blood-Based Colorectal Cancer Screening Projected to Fall Short Compared to FIT, Colonoscopy. HCPLive. March 26, 2024. Accessed March 26, 2024. https://www.hcplive.com/view/blood-based-colorectal-cancer-screening-projected-fall-short-compared-fit-colonoscopy
  12. American Gastroenterological Association. AGA responds to NEJM study on blood test for colorectal cancer screening. March 13, 2024. Accessed March 26, 2024. https://gastro.org/news/aga-responds-to-nejm-study-on-blood-test-for-colorectal-cancer-screening/
  13. US Food and Drug Administration. Colorectal Cancer: What You Should Know About Screening. Consumer Updates. March 22, 2023. Accessed March 28, 2024. https://www.fda.gov/consumers/consumer-updates/colorectal-cancer-what-you-should-know-about-screening
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