Early Diagnosis Vital for Early-Onset CRC

Veronica Hackethal

March 23, 2016

Moving forward as rapidly as possible to develop risk assessment tools is vital, so that early-onset colorectal cancer (CRC) can be diagnosed at the earliest possible stage.

That's the charge from a roundtable of survivors and family members at the Second Annual Early Age Onset Colorectal Cancer Summit, which took place March 18-19 in New York City.

The summit brought together patients, family members, researchers, physicians, and advocacy groups working to improve knowledge and awareness of early-onset CRC.

"Survivor focus groups gave a very compelling message that whatever we could do to improve outcomes would be appreciated. The key issue is timely diagnosis, making sure patients, families, and physicians are tuned in," said summit director Thomas Weber, MD, FACS, professor of surgery at the State University of New York Downstate Medical Center, in New York City, and president and founder of the Colon Cancer Challenge Foundation.

Late last year, experts in the field reached similar conclusions about the critical need for increased research into and awareness of early-onset CRC, as reported by Medscape Medical News from the Ruesch Center Symposium, held in December 2015 in Washington, DC.

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Extent of the Problem

More than 14,000 people younger than 50 years are diagnosed with early-onset CRC in the United States each year, and 3300 people die of the disease, according to data presented by Rebecca Siegel, MPH, strategic director of Surveillance Information Services at the American Cancer Society.

Although younger age groups have a much lower burden of CRC — 90% of CRC cases occur in people older than 50 years, and the incidence has been declining in recent decades -- incident rates of early-onset CRC have increased by 51% during the past 2 decades. Rates are increasing in every age group and have doubled in the youngest age group (20-29 years), though they remain low, at about 6% of cases, in persons younger than 60 years. Left-sided tumors and sporadic cases are thought to be driving the increase.

Dramatic increases in regional and distant disease have also occurred, likely because of delays in diagnosis. Only 33% of patients younger than 50 are diagnosed when the disease is at a localized stage. From 15% to 50% of early-onset CRC cases are initially misdiagnosed, and 86% are symptomatic at presentation, according to Siegel.

Patient and physician factors may account for such delays. On the part of patients, lack of recognition, embarrassment, denial, and lack of insurance may play a role. On the part of physicians, lack of screening and failure to recognize symptoms are involved.

"We need to decrease the stigma about discussing bowel symptoms between patients and doctors," Dr Weber emphasized.

Early diagnosis has an impact on outcomes. Despite rapid declines in death rates from CRC in patients older than 50, during the past decade, there has been a trend toward increasing deaths from early-onset CRC.

"It's all about educating physicians and patients about screening and increasing awareness in the general public and with primary care docs," Siegel highlighted.

A Global Problem

Other presentations during the summit added a global perspective, suggesting that early-onset CRC may be a disease of industrialized countries.

"This is a global phenomenon, and we should be working together to find solutions," emphasized Deborah Alsina, chief executive of Bowel Cancer UK.

According to Alsina, since 2004, the United Kingdom has experienced a 40% increase in the rate at which young patients are being diagnosed with stage 3 or 4 CRC, mirroring the pattern in the United States.

Being taken seriously is a problem for young patients, especially for young women. In the United Kingdom, 37% of women had to make five primary care visits before receiving a correct diagnosis of early-onset CRC, compared with 15% of men. There are reports of patients taking pictures of the amount of the blood in the toilet bowl to prove the extent of their problem.

The situation is similar in Australia and New Zealand, where 10% of CRC cases occur in young people. The incidence of early-onset CRC has been increasing there since 2000, according to Aung Ko Win, MBBS, MPH, PhD, from the Melbourne School of Population and Global Health, University of Melbourne.

Other data indicate increasing rates of early-onset CRC in Turkey, Cambodia, Israel, Egypt, Korea, and India, he added.

Environmental Risk Factors

Data presented at the summit suggest that environmental factors may play a large role in early-onset CRC.

Eighty-four percent of people with invasive early-onset colon cancers have no family history of CRC, according to registry data on adults aged 18 to 49 years from six sites in the United States, Canada, and Australia presented by Dr Win.

"The environmental factors we observed to be associated with early-onset CRC are similar to those for late-onset CRC," Dr Win said.

The hypothesized mechanism includes a proinflammatory, Western diet pattern, obesity, and physical inactivity, leading to metabolic dysregulation and inflammation, according to Christine Sardo-Molmenti, PHD, MPH, postdoctoral research scientist at the Columbia University Mailman School of Public Health, New York City.

Risk factors include obesity (especially visceral adiposity, which is highly inflammatory), age, sex (higher risk in men), alcohol, smoking, consumption of processed meat and red meat, and lack of physical activity.

"Colon cancer is a Westernized disease and is highly environmental. There is convincing evidence by world authorities that red and processed meat increases the risk of CRC, and that fiber is associated with decreased risk," commented Stephen J. D. O'Keefe, MD, FRCP, of the University of Pittsburgh, in Pennsylvania.

"Current guidelines are too low. Increasing fiber to over 50 g/day and decreasing fat by half will have a significant effect on cancer in the US, and may have an immediate effect on colon cancer," Dr O'Keefe said.

Evidence suggests that the balance between good and bad bacteria in the microbiome affects the development of CRC. This balance can be modified by diet change, according to Dr O'Keefe.

Red meat increases luminal carcinogens, he explained, and fat increases hepatic synthesis of bile acids. Bile acids that are not reabsorbed reach the colon and become secondary bile acids, which are carcinogenic. Saturated fat also stimulates inflammation through prostanoid metabolism.

By contrast, fiber escapes digestion in the small bowel and reaches the colon, where it provides food for the microbiome. The microbiome in turn ferments fiber into short-chain fatty acids, the primary energy source for the lining of the bowel. Fruits and vegetables have antioxidants and bioactive phytochemicals with antineoplastic effects, he explained.

Genetic Risk and Screening

About 10% to 15% of cases of early-onset CRC are associated with known genetic factors, such as Lynch syndrome and familial adenomatous polyposis (FAP). Some of the remainder may be associated with other, unknown genetic factors, according to Dr Win.

Evidence of a possible genetic connection is being explored in the Acadian region of southern Louisiana, a founder population that came from Nova Scotia, Canada. Data from the Surveillance, Epidemiology and End Results Program and Louisiana Tumor Registry presented by Jordan Karlitz, MD, from Tulane University School of Medicine, New Orleans, suggest that in the Acadian region of Louisiana, the rate of early-onset CRC is 27% higher than in the general population in the United States. A study is currently underway to look for evidence of Lynch syndrome in this population.

"I think we cannot ignore the possibility of genetics being involved in sporadic early CRC cases," agreed Zosia Stadler, MD, of Memorial Sloan Kettering Cancer Center, New York City.

Screening

At present, only age and family history are used for US screening guidelines, and there is a need to know more, according to Dennis Ahnen, MD, FACG, of the University of Colorado School of Medicine, in Aurora.

At any age, risk is higher in men than women. African Americans are also at increased risk for CRC and should be screened before age 50, he said.

In general, people in need of early screening include those with FAP (beginning at age 10 to 12 years), Lynch syndrome (beginning at age 20 to 25 years), inflammatory bowel disease (varies depending on age of onset), CRC/adenoma in a first-degree relative (age 40 years or 10 years before youngest case), and more than two CRCs in second-degree relatives (age 40 years).

Next Steps

To improve earlier diagnosis of early-onset CRC, Dr Weber and colleagues are working on an early-onset CRC symptoms and signs index, which is in development and still requires validation.

"Early-onset CRC is a major cancer control challenge, no matter what anyone tries to say," Dr Weber stressed. "The problem is complex and multifactorial, and there are rich opportunities to make a difference."

Second Annual Early Age Onset Colorectal Cancer Summit: March 18-19, 2016.

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