Young-onset esophageal adenocarcinoma: Results from a population-based study

April 17, 2021

Researchers have recently noted that the incidence of esophageal adenocarcinoma (EAC) is increasing within the United States and other Western countries. This form of cancer is most often diagnosed in people age 50 and older, and limited data are available about its impact on younger individuals. To better understand the epidemiology and outcomes of "young-onset" EAC in people under age 50, Mayo Clinic researchers conducted a large population-based study that examined the incidence, stage distribution and survival outcomes associated with EAC. The results of this study were published in Cancer Epidemiology, Biomarkers & Prevention in 2021.

Study methods

Mayo Clinic researchers used the Surveillance, Epidemiology, and End Results (SEER) database to identify 34,443 patients diagnosed with histologically confirmed EAC between 1975 and 2015. The SEER 9 database release comprises a significant sample (approximately 35%) of the U.S. population and includes data from 18 geographic regions.

The researchers subdivided patients diagnosed with EAC into three age groups: under age 50, ages 50 to 69, and age 70 and older, and they classified each patient's cancer stage at presentation as localized, regional or distant. They then assessed trends in incidence, disease stage and survival during three time periods (1975-89, 1990-99 and 2000-15) and created univariate and multivariate models to identify predictors of mortality.

Study results

According to Don (Chamil) C. Codipilly, M.D., and Prasad G. Iyer, M.D., the article's first and corresponding authors, the research team's findings offer data that challenge traditional thinking about EAC, and these findings merit further study. Dr. Codipilly is a gastroenterology fellow, and Dr. Iyer is a gastroenterologist and researcher at Mayo Clinic's campus in Rochester, Minnesota. Dr. Iyer's research focuses on identifying noninvasive techniques for the early detection of esophageal neoplasia.

"Our results suggest that people under age 50 are getting diagnosed with this disease at a higher rate than previously thought, and at a later stage than older populations. And this difference ultimately leads to poorer cancer-related survival among the younger patients," explains Dr. Codipilly.

Below are a few of the interesting data points about the incidence, presentation and outcomes of young-onset EAC that Drs. Iyer, Codipilly and co-authors shared:

  • Overall, while the proportion of people under age 50 diagnosed with EAC constitutes less than 10% of the total number of people diagnosed with this cancer, the annual incidence of EAC in this age group has increased by more than threefold from 1975 to 2015 (from 0.08/100,000 to 0.27/100,000).
  • Patients under age 50 diagnosed with EAC were more likely to present with more-advanced cancer stages (regional and distant) than were patients in older age groups (84.9% versus 67.3%).
  • Patients under age 50 diagnosed with EAC had poorer five-year cancer-free survival rates than did those in older age groups (22.9% versus 29.6%), a finding that appears to be linked to the advanced stage at presentation.
  • Young-onset EAC occurred more frequently in men than in women over the 40-year period studied. In 1975, 90% of patients under age 50 diagnosed with EAC were men, and in 2015, 86.4% were men.

The Mayo Clinic researchers also note that several factors could be responsible for delayed diagnosis of EAC in younger patients, including:

  • A lack of clinical suspicion (for malignancy) in young patients presenting with dysphagia
  • A lack of screening and surveillance recommendations for Barrett's esophagus in people under age 50
  • The fact that younger individuals seek care less frequently than older individuals

Future research

Additional research is required to determine the biologic, genetic and environmental factors that account for the higher proportion of advanced disease identified in younger patients. "It would be vitally important to assess if the genetic makeup of cancers affecting younger versus older patients is different, as that may explain the aggressive nature of this disease in younger patients," says Dr. Iyer.

One possible explanation for the higher proportion of advanced disease identified in younger patients may be related to what drives the transition from intestinal metaplasia to EAC in younger patients. "These cancers may undergo a more rapid transition from intestinal metaplasia to esophageal adenocarcinoma," explains Dr. Iyer. "This accelerated transition could be driven by an increase in signaling molecules that are active in the intestine, or this form of esophageal adenocarcinoma could be driven by a process independent of intestinal metaplasia."

Clinical implications

The Mayo Clinic researchers note that until future research clarifies some of the questions raised here, their findings suggest that current diagnostic and management strategies for patients under age 50 may need to be reevaluated.

"While it probably is not economically feasible to screen all young people for this cancer, this data shows that it is important for practitioners — both gastroenterologists and primary care providers — to avoid ignoring or minimizing symptoms among patients in this age group," says Dr. Codipilly. "We need to gain a better understanding of both patient and physician perceptions of symptoms that could indicate esophageal cancer. Further, younger people who are diagnosed with Barrett's esophagus, a premalignant condition, may require more-intensive cancer surveillance than current guidelines suggest."

For more information

Codipilly DC, et al. Epidemiology and outcomes of young-onset esophageal adenocarcinoma: An analysis from a population-based database. Cancer Epidemiology, Biomarkers & Prevention. 2021;30:142.