The incidence of colorectal cancer continues to increase among young adults, with the sharpest increase among those aged 20 to 29, according to a recent article in the Journal of the National Cancer Institute.1 This trend has been called disturbing and ominous, but the widely reported results of this and previous studies2-4 serve to increase awareness of colorectal cancer in younger adults, raise the level of suspicion among physicians, and could lead to earlier detection.
“Young patients are 58% more likely than older patients to be diagnosed with distant- vs localized-stage [colorectal cancer], largely due to delayed follow-up of symptoms, sometimes for years, because cancer is typically not on the radar of young adults or their providers,” the study authors wrote.
This isn’t the first article to support this finding, and I do think there is an increased awareness [of colorectal cancer in younger patients]. But it takes time for these things to penetrate.— John L. Marshall, MD
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“We are seeing a shift already,” John L. Marshall, MD, told The ASCO Post. “This isn’t the first article to support this finding, and I do think there is an increased awareness. But it takes time for these things to penetrate, and so the hope is that the more we beat the drum, the more people will recognize it.” Dr. Marshall is Director, The Ruesch Center for the Cure of Gastrointestinal Cancers, and Chief, Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
Younger Patients With Colorectal Cancer
The percentage of younger patients with colorectal cancer seen at the Georgetown University clinic is increasing, with more than half of the patients under age 50 and recently including a patient younger than age 20. Dr. Marshall explained that Washington, DC, does have a younger population than many other U.S. cities, and “when you are at a cancer center like ours, it shifts toward younger people in general compared to the community.” Even so, “when you talk to other doctors, many can tell you that they have, for example, a 20-year-old as a patient with colorectal cancer, and it surprises them.”
Accumulating evidence from studies can diminish the surprise and trigger testing. “Patients need to be aware of the symptoms, and if they have symptoms and present to a primary care physician, they need to be ready to undergo testing,” Dr. Marshall said. He likened it to the educational component that previously accompanied breast self-examination. “For women finding lumps, there was a very high sensitivity predisposing them to get screened right away. We need a similar kind of trigger for colon cancer.”
Double and Quadruple Risk
The latest study used data from the 9 oldest Surveillance, Epidemiology, and End Results (SEER) registries to analyze colorectal cancer incidence trends by 5-year age group and birth cohorts among 490,305 patients aged 20 years and older who were diagnosed with colorectal cancer between 1974 and 2013.
“After decreasing in the previous decade, colon cancer incidence rates increased by 1.0% to 2.4% annually since the mid-1980s in adults aged 20 to 39 years and by 0.5% to 1.3% since the mid-1990s in adults aged 40 to 54 years; rectal cancer incidence rates have been increasing longer and faster (eg, 3.2% annually from 1974–2013 in adults aged 20–29 years). In adults aged 55 years and older, incidence rates generally declined since the mid-1980s for colon cancer and since 1974 for rectal cancer,” the study authors reported.
“Age-specific relative risk by birth cohort declined from circa 1890 until 1950 but continuously increased through 1990. Consequently, compared with adults born circa 1950, those born circa 1990 have double the risk of colon cancer (incidence rate ratio [IRR] = 2.40, 95% confidence interval [CI] = 1.11–5.19) and quadruple the risk of rectal cancer (IRR = 4.32, 95% CI = 2.19–8.51),” they added.
More Distal Cancers
“Increasing trends in adults younger than age 50 years were confined to tumors in the distal colon, with the exception of adults aged 40 to 49 years, among whom rates are also increasing for proximal tumors,” the authors noted.
The main reason for the increase in incidence is the increase in the rate of rectal and left-sided tumors—the distal colon cancers.— Mohamed E. Salem, MD
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“The main reason for the increase in incidence is the increase in the rate of rectal and left-sided tumors—the distal colon cancers,” Mohamed E. Salem, MD, said in an interview with The ASCO Post. “Why is this relevant? Because last year at the 2016 ASCO Annual Meeting, Dr. Alan Venook presented data showing there is an actual difference between left- and right-sided tumors.5 They behave differently and perhaps even respond differently to some of the drugs we have. You also have to wonder, is there something different about those younger people coming in with left-sided colon cancer now?” Dr. Salem is a gastrointestinal oncologist and Assistant Professor of Clinical Medicine, Associate Fellowship Program Director, Division of Hematology and Oncology, also at Lombardi Comprehensive Cancer Center.
Some retrospective studies have hinted that colorectal cancer may be more aggressive in young people, but “we are not sure yet,” Dr. Salem stated. Research conducted at Georgetown University and reported at the 2016 Gastrointestinal Cancers Symposium6 reviewed molecular profiles of tumors obtained from younger and older patients. “Indeed there were differences, some associated with more aggressive biology and some associated with factors we can target with therapy,” Dr. Salem said. “When we looked at our own data, younger people had a higher percentage of HER2 amplification.”
Other studies have shown that patients with Lynch syndrome and colorectal cancer respond to immunotherapy drugs. “We are moving toward an era where one size does not fit all anymore. We are moving toward precision medicine, and we have to tailor our treatment to each individual patient,” he commented.
Beware of Overtreating
While colorectal cancer may not be initially suspected in a younger person, once it is detected, both patients and physicians may tend to be overzealous in treating the cancer. “When patients who are 25 or 35 are told they have stage IV colon cancer, they come to us and say, ‘I want to get rid of this. I want to be cured.’ Unfortunately, as much as we hope to, the reality is that most of the time, we are not able to cure them,” Dr. Salem said.
“So young patients often say, ‘I want aggressive treatment.’ I warn them that younger patients usually receive more surgery and more chemotherapy than older patients, yet the outcome is still the same.7 So the treatment has to be balanced. It is up to the oncologist to be conscious of this and able to make this point,” Dr. Salem emphasized.
“Yes, we want to cure these young patients, but we don’t want to overtreat them, because this is associated with a lot of toxicity. These young patients still need to go out, enjoy their lives, be with their families, and do their jobs. Part of what we do concerns not just the treatment of the patient. We have to be very conscious about what is going on in their lives—the social, emotional, and economic aspects,” he said.
“[Colorectal cancer in younger patients] has a huge impact, not just on the patient, but on the whole community,” he continued. “If you are a 75-year-old person who has colon cancer, probably you have already paid off your mortgage; your kids have grown up and, most likely, graduated from school; you aren’t looking to have more children; and you are already retired. On the other hand, if you are 20 or 30 or 40 years old, most likely, you are still working and need to take care of your children or, perhaps, want to start a family. Treatment will have an impact on fertility and pregnancy, as well as on your partner and children. Someone is going to need to take time off work and come with you for treatment and support you. If you are an even younger person, perhaps you don’t have a job yet and are on your parents’ health insurance. If [the health insurance laws] change, and young people cannot be covered or don’t have access to health insurance, that is a big problem.”
Most Cases Are Sporadic
The study authors reported:
While early-onset [colorectal cancer] has a familial component more often than late-onset disease, the majority of cases are sporadic. The rise in [colorectal cancer] in young adults has likely been attenuated by long-term declines in alcohol consumption and smoking but fueled by increases in cumulative exposure to excess body fat, which have been demonstrated by studies of obesity trends by birth cohort. It is not surprising that the timing of the obesity epidemic parallels the rise in [colorectal cancer] because many behaviors thought to drive weight gain … independently increase [colorectal cancer risk]. Moreover, there are undoubtedly complex epigenetic interactions between obesity, sedentary behavior, and diet.
“The honest truth is nobody knows 100% why there is an increase [in colorectal cancer among younger people],” Dr. Salem said in The New York Times.8 “It’s hard to blame it on obesity alone. We suspect there is also something else going on.”
That “something else,” he told The ASCO Post, may be related to the molecular profile and underlying genomic alterations.
In an Associated Press article on the study, Dr. Marshall noted that few of the younger patients with colorectal cancer have traditional risk factors. “Other suspects include changes in the protective bacteria that line people’s digestive tracts.”9
In an interview with The ASCO Post, Dr. Marshall elaborated, “The bacteria that live in and around us are incredibly important to our health and biology, and we are only beginning to understand that. Whether it is digestive diseases, infectious diseases, allergies—all of them are affected by the bacteria. In fact, the linkage between the immune system and the bacteria in our colon is increasingly being recognized. Those who are now studying this have clearly shown that there are some bacteria that are carcinogenic and others that are protective. There is a fine balance that we are supposed to be maintaining.”
He likened this balance to that needed to maintain a coral reef. The bacteria in the colon “need to be in balance, and somehow, with our changing lifestyles, our fear of germs, our handwashing, our quick use of antibiotics, and the like, we have changed our bacterial flora, and there are signs to support that.” He noted that this is just one of the theories proposed for the increase in colon cancer, but it would fit his experience with some patients—“people who are educated, exercise, eat right, do not have the kind of bad habits that we associate with cancer, and here they are at 20 or 30 years old with colon cancer.”
Adherence to Screening Guidelines
The study authors stated that their finding of rising colorectal incidence rates “for people in their early 50s, as well as younger age groups, highlights the need for increased adherence to recommended screening.” Current guidelines call for screening to start at age 50 for individuals at average risk and earlier for those at increased risk, which includes people with a family history of colorectal cancer or adenomatous polyps. “Despite these recommendations, among people with an affected first-degree relative, those younger than age 50 years are half as likely to have had a colonoscopy as those aged 50 years or older,” according to the study report.
“Increasingly, people know about the hereditary colon cancer syndrome, Lynch syndrome, but that doesn’t account for a lot of people with a ‘family history,’” Dr. Marshall said. The reality, he added, is “we don’t know who needs to be screened and who needs to be screened earlier. This trend in younger people is in some ways independent of family history. Almost all of these people do not have the genetic syndrome, do not have a first-degree relative with colon cancer. So, this is a new phenomenon that doesn’t fit with our previous conceptions.”
Begin Screening Earlier?
“Beginning screening at age 45 years is not supported by a recent review of the evidence for colorectal cancer screening and would add approximately 20 million people to the screening-eligible population,” the study authors pointed out. They added, however, “Endoscopic screening could be particularly useful in stemming the tide of tumors in the distal colon and rectum, which are preponderant in young patients.” Noting that the proportion of rectal cancer cases diagnosed in people under age 55 has doubled in the past 2 decades, with these people now accounting for one-third of rectal cancer patients, the authors concluded, “screening initiation before age 50 should be considered.”
“That is an easy thing to say, but the implications of that on a public health level are a big deal,” Dr. Marshall stated. Screening with colonoscopy is not an easy process, he remarked. “It is an invasive, expensive, unpleasant test, and it is not clear that it is going to have an impact on this emergence in younger people. The screening guidelines are based on traditional colon cancer, starting at age 50, looking for polyps that take 5 to 15 years to evolve into cancer. What we don’t know is whether the biology of these younger patients’ cancers is even a good setup for screening: Is there is a precursor lesion, a benign thing that we could identify and remove earlier and prevent the disease from happening? Before we make any major shifts in screening recommendations, we need to understand the biology, both to save people from going for tests they won’t need or won’t help and to save our overall health-care budgets.”
Dr. Salem agreed that whether to move the screening age to “below 50, perhaps 40 or 45, is not an easy question. It has to be proven that it is actually cost-effective and saves lives.” Current screening, “mostly with colonoscopy, starts at age 50 for someone who has no family history, no genetic abnormality, and no high-risk features,” Dr. Salem noted. “But the problem is that 3 out of every 10 patients are diagnosed below age 55. These people actually have the disease even before the age of screening.”
Otis W. Brawley, MD, FACP
In response to the study authors’ suggestion that it might be time to reconsider screening before age 50 for average-risk individuals, Otis W. Brawley, MD, FACP, Chief Medical Officer of the American Cancer Society, stated: “These new data will be examined by our independent guidelines development group to review whether a change in our screening recommendations is warranted, particularly since screening can prevent colorectal cancer, averting substantial morbidity and mortality during the most productive years of life.”10 ■
Disclosure: Drs. Marshall and Salem reported no potential conflicts of interest.
References
1. Siegel RL, Fedewa SA, Anderson WF, et al: Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst 109:djw322, 2017.
2. Singh KE, Taylor TH, Pan C-J G, et al: Colorectal cancer incidence among young adults in California. J Adolesc Young Adult Oncol 3:176-184, 2014.
3. Bailey CE, Hu CY, You YN, et al: Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 150:17-22, 2015.
4. Abdelsattar ZM, Wong SL, Regenbogen SE, et al: Colorectal cancer outcomes and treatment procedures in patients too young for average-risk screening. Cancer 122:929-934, 2016.
5. Venook AP, Niedzwiecki D, Innocenti F, et al: Impact of primary (1º) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). 2016 ASCO Annual Meeting. Abstract 3504. Presented June 3, 2016.
6. Heeke AC, Xiu J, Reddy SK, et al: Molecular characterization of colorectal tumors in young patients compared with older patients and impact on outcome. 2016 Gastrointestinal Cancers Symposium. Abstract 505. Presented January 21, 2016.
7. Kneuertz PJ, Chang GJ, Hu CY, et al: Overtreatment of young adults with colon cancer: More intense treatments with unmatched survival gains. JAMA Surg 150:402-409, 2015.
8. Rabin RC: Colon and rectal cancers rising in young people. The New York Times, February 28, 2017.
9. Neergaard L: Colorectal cancer rare but rising among millennials, generation X. Associated Press, February 28, 2017.
10. Simon S: Report: Colon and rectal cancer rates continue to drop among older Americans. American Cancer Society, March 1, 2016. Available at www.cancer.org. Accessed March 22, 2017.
