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Over the past 4 decades, the incidence of esophageal adenocarcinoma (EAC) has increased in the U.S. in individuals younger than 50, according to a large population-based study.

From 1975 to 2015, the annual percentage increase was 2.9% (95% CI 1.4-4.4), reported Prasad G. Iyer, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.

As they explained in their study online in , while young-onset disease still makes up less than 10% of all cases of EAC, the incidence has increased by more than 200% during this period. Moreover, the disease has presented at more advanced stages compared with older patients and was associated with shorter disease-free survival.

"Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated," the researchers wrote.

EAC is a relatively rare cancer, with expected to be diagnosed in the United States this year, according to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. While those cases account for only about 1% of all cancer diagnoses in the U.S., EAC is associated with poor outcomes, with a 5-year survival rate of only about 20%.

Interestingly, several of the new study's findings mirrored trends in young-onset colorectal cancer (CRC), the investigators noted, with patients younger than 50 making up approximately 5-10% of all cases. Over the past 30 years, the incidence of young-onset CRC has by a comparable 2% per year, and younger patients are also more likely to present with more advanced disease.

Recent research has also shown a disproportionately rapid rise in the "health-conscious" western states. While the factors driving this CRC trend are unclear, speculation has included alterations in the gut microbiome due to dietary changes such as increased intake of highly processed foods and high glycemic load carbohydrates, antibiotic use, and food additives, including high fructose corn syrup and emulsifiers.

Study Details

For the EAC study, Iyer and co-authors assessed information about patients diagnosed from 1975 to 2015 in the SEER 9 database, which incorporates data from 18 geographic regions in the U.S., representing approximately 35% of the U.S. population. The analysis was separated into three age strata: younger than 50, 50 to 69, and 70 and over.

Of the total 34,443 cases of EAC cases during that time, 86.2% occurred in males in all three age groups, and 95% occurred in white patients, both male and female.

With cancers staged as localized, regional, and distant, trends in incidence, disease stage, and survival were analyzed for 1975-1989, 1990-1999, and 2000-2015, and univariate and multivariate models identified predictors of mortality.

The results showed that during the years 2000-2015:

• More advanced (regional/distant) disease made up young-onset EAC: 84.9% of young patients vs 77.3% in patients 50 to 69 and 67.8% in those 70 and older (P<0.01)

• The proportion of patients with young-onset EAC presenting with regional/distant disease also increased over time: 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P<0.01), a faster rate than that in older age groups, the researchers noted

• Younger patients had lower 5-year EAC-free survival rates compared with older patients: 22.9% vs 29.6% (P<0.01), although this finding was attenuated on stage-stratified analysis

Commenting in a press release, co-author Don C. Codipilly, MD, also of the Mayo Clinic, said: "Physicians must keep in mind that EAC is not a disease of the elderly, and that outcomes for young people with EAC are dismal. Our findings suggest that physicians should have a low threshold of suspicion for patients who present with dysphagia. While younger patients would typically not be at high risk for EAC, they may benefit from an upper endoscopy."

Asked for his perspective, Hashem B. El-Serag, MD, MPH, director of the Texas Medical Center Digestive Diseases Center of Baylor College of Medicine in Houston, who was not involved with the research, said it took a nationwide population-based study to record sufficient cases to identify the upward trend in young-onset EAC. He said that so far he has not seen an uptick at his center since the case numbers are too few.

As to possible drivers of the trend, he noted rising obesity rates in younger individuals leading in turn to chronic gastroesophageal reflux disease [GERD] at an early age. "Both of these are established risk factors for Barrett's esophagus and esophageal adenocarcinoma," El-Serag told 乌鸦传媒. "GERD that starts during childhood is also known to persist as a chronic condition in adulthood, and it's possible that the reported increase in childhood GERD also underlies the observed trends in esophageal adenocarcinoma."

Also speculating about possible reasons for the increase, Iyer and co-authors wrote: "While it is unclear at this time what biologic, genetic, or environmental factors may influence these findings, until such factors are elucidated, reevaluation of our diagnostic and treatment strategies in this age group might need to be considered."

Limitations of this study, the team said, included the inability to thoroughly review individual health records to confirm disease stage and other patient variables at diagnosis, and there was also a disproportionate number of cases in white patients, which precluded true comparison of outcomes across races. In addition, comorbidity information, which could help identify a high-risk population, was not available in the SEER 9 database. Information on chemotherapy and radiotherapy was also unavailable for a large subset of cases, and so was not included in the primary analysis, although a subset analysis of patients with these data available found that a lack of therapy was associated with poorer EAC-free survival, the researchers said.

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