Achalasia associated with fivefold higher risk for esophageal cancer
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CHARLOTTE, N.C. — Achalasia was associated with an increased risk for esophageal cancer among a cohort of veterans, suggesting the need for increased endoscopic surveillance, according to a presenter at the ACG Annual Scientific Meeting.
“Achalasia is a postulated risk factor for esophageal cancer. The suggested cause of pathophysiology relates to stasis esophagitis,” Eric E. Low, MD, MPH, an internal medicine resident at the University of California, San Diego, said. “Esophageal cancer-associated risk and outcomes in individuals with achalasia have been understudied, and as such, there are no guidelines for surveillance endoscopy for those with achalasia.”
Seeking to evaluate the risk for esophageal cancer among patients with achalasia vs. those without achalasia, Low and colleagues matched 1,866 veterans with achalasia to 7,464 veterans without achalasia, all who received care through the Veterans Health Administration between 1999 and 2020. The median age of participants was 55 years and 92% were men.
Over the study period, researchers reported 17 cases of esophageal cancer among veterans with achalasia and 15 cases of esophageal cancer among veterans without achalasia. The median time from achalasia diagnosis to cancer development was 3 years, and those with achalasia had more than fivefold increased risk for esophageal cancer (HR = 5.4; 95% CI, 2.8-10.5) compared to those without.
Researchers also reported a higher cumulative incidence of esophageal cancer among those with vs. without achalasia at 5-, 10- and 15-years follow-up.
Post-hoc analysis further revealed Candida esophagitis preceded cancer diagnosis (median time, 1.3 years) in 12.5% of veterans, and patients with vs. without Candida esophagitis had an 18.3-fold higher risk for esophageal cancer (95% CI, 6.2-53.7).
“Using a nationwide cohort of individuals with achalasia, we found a 5.4-fold increased risk of esophageal cancer among individuals with vs. without achalasia,” Low concluded. “The implications for this are that individuals with achalasia may benefit from a high index of suspicion and endoscopic surveillance for esophageal cancer.”
“We also found that Candida esophagitis exposure was associated with esophageal cancer risk,” he continued. “More research is needed to understand whether Candida contributes to esophageal cancer pathogenesis or is merely a manifestation of more severe statis that may be driving esophageal cancer risk.”
Perspective
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Yi Qin, MD
This is an award-winning abstract that detailed an important but elusive topic studied in a large veteran population. Achalasia is a rare condition with a prevalence of about one per 10,000 people; esophageal cancer also is a relatively rare malignancy. It has long been observed that the risk for esophageal cancer, especially esophageal squamous cell carcinoma, is higher in patients with achalasia. The underlying mechanism is thought to be due to stasis, but the increased risk persists after treatment for achalasia.
The authors observed more than fivefold increased risk for esophageal cancer in patients with achalasia, which is in line with previous studies. What is new is that they observed a more than 18-fold increased risk in patients with achalasia who also have Candida esophagitis. Candida esophagitis reflects the degree of stasis but may also carry an oncogenic mechanism through its own inflammatory process. It would be important to answer the question of whether cancer risk is due to stasis alone or inflammation specific to Candida infection. It also would be important to distinguish the types of esophageal cancer — esophageal adenocarcinoma vs. esophageal squamous cell carcinoma — observed in patients with achalasia, as the pathomechanism for each is different.
Finally, the study reports that the median time to cancer development in patients with achalasia was 3 years from diagnosis of achalasia. It would be critical to exclude patients who were misdiagnosed with achalasia and actually had pseudoachalasia from esophageal cancer.
This study further adds to the body of evidence that achalasia is associated with increased risk for esophageal cancer, and that there are factors — stasis vs. inflammation — that further increase that risk.
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Low EE, et al. Abstract S388: Risk of esophageal cancer in achalasia: A matched cohort study utilizing the veterans affairs achalasia cohort (VA-AC). Presented at: ACG Annual Scientific Meeting; Oct. 21-26, 2022; Charlotte, N.C. (hybrid meeting).
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