In clinical practice, Samantha Hendren, MD, MPH, has been “shocked by what a large proportion of patients we are seeing who are under 50 and presenting with colorectal cancer,” often with advanced disease due to delayed diagnosis. “And that is because patients and physicians don’t even think of colorectal cancer when younger people come in with symptoms,” Dr. Hendren, Associate Professor of Colorectal Surgery at University of Michigan Health Systems, Ann Arbor, told The ASCO Post.

Samantha Hendren, MD, MPH

Dr. Hendren expressed hope that a recent study on the prevalence of colorectal cancer among those considered “too young for average-risk screening” will lead to earlier diagnosis and treatment of these patients. The results of that study “mirror what we are noting in our clinical practice: an increasing number of very young patients with colorectal cancer, who are often symptomatic and with a delay in diagnosis,” Dr. Hendren and colleagues reported in Cancer.¹ The results also emphasize the need to consider colorectal cancer in young patients who present with the “red-flag” symptoms of hematochezia, anemia, or a change in bowel habits. 

This message got a boost from coverage of the study by health and medical media, as well as the popular press, including the New York Daily News and Reuters,^2,3 both with quotes from Dr. Hendren. “One of our goals in talking about this article is to raise awareness among the population and primary care providers about the fact that there are more patients under 50 with colorectal cancer than you might think.”

Regional and Metastatic Disease More Likely

The study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) registry for patients aged 20 to 79 who were diagnosed with colorectal cancer between 1998 and 2011. Patients were categorized as being younger or older than the recommended screening age of 50 and up for those at average risk of colorectal cancer. The mean age of patients too young for average-risk screening was 42.5 ± 6.0 years. There were slightly more males (54%) in both age groups. 

Among the 258,024 patients in the SEER registry diagnosed with colorectal cancer, 37,847 (15%) were aged < 50 years, a somewhat higher percentage than the national average. “That is because we excluded patients 80 and older. If you look at the entire U.S. population, it is about 10% of colorectal cancer patients who are under 50,” Dr. Hendren pointed out. 

“Young patients were more likely to present with regional (relative risk ratio = 1.3, P < .001) or distant (relative risk ratio = 1.5, P < .001) disease,” the study found, although patients with rectal cancer were significantly less likely to present with advanced stages of disease compared with patients with colon cancer. The greater likelihood of more advanced disease “may be explained largely by the finding that current screening guidelines do not recommend routine screening for this apparently low-risk population,” the authors noted.

Treated More Aggressively

Younger patients with colorectal cancer and distant metastasis were more likely to receive surgical therapy for their primary tumor (adjusted probability = 72% vs 63%, P < .001) and radiotherapy (adjusted probability = 53% vs 48%, P < .001). This finding of more aggressive treatment “could demonstrate the potential overuse of primary tumor resection in younger patients,” according to the study report. 

“It is very much something that is debated in the surgical community that treats colorectal cancer,” Dr. Hendren commented. “There have been a couple of relatively small studies showing that patients with metastatic colorectal cancer should not jump into having the primary tumor resected. But that being said, patients with a limited amount of metastatic disease, who are otherwise in good health, are often candidates for aggressive surgical therapy that would resect both the primary and the metastatic disease. So I am not too surprised that more of these younger patients are getting surgery for the primary tumor, even if they have metastatic disease, because I think that they can be appropriately treated more aggressively than somebody who is much older. We see that in our practice.” 

Because of its reliance on SEER data, the study could not assess the use of chemotherapy. “Although SEER does not contain accurate data regarding chemotherapy use, the results of the current study add to the growing literature concerning the patterns of therapy for patients with colorectal cancer and indicate that younger patients are indeed treated more aggressively,” the investigators stated. 

Better Disease-Specific Survival 

Longer life expectancy also factors into the decision to use more aggressive treatment in younger patients. “Despite the fact that the younger patients are diagnosed at a later stage, they still have an essentially equivalent 5-year survival,” Dr. Hendren said—67.7% vs 66.8% (P = .008) for older patients. “I think that is related to having overall good health and being able to undergo probably a little more aggressive treatment than you would give to somebody who is much older.”

Despite a larger percentage of patients presenting with advanced disease, younger patients had better overall disease-specific survival (hazard ratio = 0.77, P < .001). The respective 5-year disease-specific survival rates for younger vs older patients were 95.1% vs 91.9% for localized disease, 76% vs 70.3% for regional disease, and 21.3% vs 14.1% for distant disease. 

Promoting Practice Changes 

“In the realm of current practice improvement, this study is a wake-up call to the medical community regarding the increasing prevalence of [colorectal cancer] in young patients,” Dr. Hendren and her coauthors wrote. 

Expanding on that theme in the interview with The ASCO Post, Dr. Hendren said, “We have two current practice changes that we want to try to promote: One is that if people do have symptoms, such as anemia, change in bowel habits, or dark blood with bowel movements, they are really red-flag symptoms,” Dr. Hendren said. Anybody with blood in the stool not typical of a benign anorectal source, such as the bright red blood associated with hemorrhoids, “should be getting a colonoscopy,” Dr. Hendren said.

The second change is to pay more attention to a patient’s family history of colorectal cancer. “People who have a history of colorectal cancer in their immediate family—whether a brother, a sister, or a parent—are at double the risk for getting colorectal cancer. And those patients should actually start screening at 40, not 50. We are quite sure that a lot of Americans are not aware of that, and we want to try to raise awareness about it. Because if patients are at increased risk, they need to be getting that early screening,” Dr. Hendren explained. 

She noted that the defining conditions for people at high risk are spelled out in American Cancer Society guidelines, which recommend that some individuals “might need to start colorectal cancer screening before age 50 and/or be screened more often.”⁴ 

Racial and Ethnic Considerations

The study also found that younger patients with colorectal cancer were more likely to be African American, American Indian/Alaska Native, or Asian/Pacific Islander. 

“We have known for a while that African Americans are at slightly increased risk of colorectal cancer. It hasn’t been very carefully studied in other populations, just because the absolute numbers of Americans of other ethnic populations are not as great,” Dr. Hendren said. “Right now, there isn’t an official recommendation to start screening at an earlier age for any specific ethnic populations,” she added, “but it is critical to get that screening at 50, or if you have other risk factors, at 40. Those risk factors include a first-degree relative with colorectal cancer and the development of symptoms—changes in your bowel movements, anemia, dark bleeding. Those things should really be taken seriously.” 

Should the Screening Age Be Lowered?

Do the increasing incidence and later diagnosis of colorectal cancer among those now considered too young for average-risk screening mean that the screening age should be lowered?

“That is the first thing that we thought of—should we be screening at a younger age? But it would take a lot of research to sort that out,” Dr. Hendren remarked. 

She and her co-investigators stated, “the increasing rate of early-onset colorectal cancer would suggest that we should consider low-cost/low-risk screening with fecal immunochemical test kits or fecal DNA tests for the entire population at an earlier age (eg, age 40 or 45 years),” but the cost-effectiveness needs to be tested. 

Dr. Hendren explained that any effort to revise guidelines needs to take into account three issues. “One is the financial cost to the health-care system of changing the screening age, which would be substantial. The second is the potential for major and minor complications of screening. We know that about 1 in 1,000 people who have a colonoscopy has a complication. These complications can be very serious, and we don’t want to expand the population of people getting that test unless we feel pretty confident that we are going to help more people than we are hurting,” she said. 

The third issue is related to stress and anxiety. “As we have seen with mammography screening for breast cancer, there is also a lot of stress and anxiety arising from false-positive colorectal screening tests. Just the process of going through cancer screening can be very stressful,” she said, and the harm would outweigh the benefits “if we are not picking up cancers and preventing deaths.”

Epidemiologic studies can be performed, she said, “to weigh all those risks and benefits and try to come to a better conclusion.” She expressed hope that the current study would spur epidemiologic research on the cost vs the benefit of earlier testing. 

“Future clinical and basic science research will be required to identify characteristics of patients with early-onset [colorectal cancer] who are without a family history that might be useful for risk stratification,” the investigators wrote. “We can imagine a future in which more universal genetic testing for cancer and other disease risk factors would allow for such risk stratification.” ■

Disclosure: Dr. Hendren has received research funding from the National Cancer Institute and the American Society of Colon and Rectal Surgeons’ Research Foundation.

References

1. Abdelsattar ZM, Wong SL, Regenbogen SE, et al: Colorectal cancer outcomes and treatment procedures in patients too young for average-risk screening. Cancer. January 25, 2016 (early release online).

2. Cutler J: Study suggests lowering the age for first colonoscopy to 40. New York Daily News, January 25, 2016.

3. Rapaport L: Some colorectal cancers found before screening starts at age 50. Reuters, January 25, 2016.

4. American Cancer Society recommendations for colorectal cancer early detection. Last revised February 1, 2016. Available at www.cancer.org. Accessed February 22, 2016.