Esophageal Cancer Prevention (PDQ®)–Health Professional Version

SECTIONS

Overview

Note: Separate PDQ summaries on Esophageal Cancer Screening, Esophageal Cancer Treatment, and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Who Is at Risk?

Smoking and drinking alcohol may account for roughly 90% of esophageal squamous cell carcinoma cases in Western countries like the United States.[1] Gastroesophageal reflux/Barrett esophagus is associated with an increased risk of esophageal adenocarcinoma. Other factors that may explain the increased risk of adenocarcinoma of the esophagus include obesity [2] and the use of medications such as anticholinergics that can predispose to gastroesophageal reflux disease (GERD) by relaxing the lower esophageal sphincter.[3]

Squamous Cell Carcinoma of the Esophagus

Factors with adequate evidence of increased risk of squamous cell carcinoma of the esophagus

Cigarette smoking and drinking alcohol

Based on solid evidence, smoking cigarettes and drinking alcohol increases the risk of esophageal squamous cell carcinoma. Smoking and drinking alcohol may account for roughly 90% of esophageal squamous cell carcinomas in Western countries like the United States.[1]

Magnitude of Effect: Increased risk, moderate magnitude.

Study Design: Evidence from population-based case-control and cohort studies.
Internal Validity: Fair.
Consistency: Good.
External Validity: Fair.

Factors with adequate evidence of decreased risk of squamous cell carcinoma of the esophagus

Avoidance of tobacco and alcohol

Based on solid evidence, avoidance of tobacco and alcohol would decrease the risk of squamous cell carcinoma.[1,4]

Magnitude of Effect: Large positive benefit.

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Fair.
Consistency: Multiple studies.
External Validity: Fair.

Chemoprevention

Aspirin and nonsteroidal anti-inflammatory drug (NSAID) use

Benefits

Based on fair evidence, epidemiologic studies have found that aspirin or NSAID use is associated with decreased risk of developing or dying from esophageal cancer (OR, 0.57; 95% CI, 0.47–0.71).[5]

Magnitude of Effect: Small positive.

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Fair.
Consistency: Good.
External Validity: Fair.

Harms

Based on solid evidence, harms of NSAID use include upper gastrointestinal bleeding and serious cardiovascular events, such as myocardial infarction, heart failure, hemorrhagic stroke, and renal impairment.

Magnitude of Effect: Increased risk, small magnitude.

Study Design: Evidence obtained from randomized controlled trials.
Internal Validity: Fair.
Consistency: Good.
External Validity: Fair.

Adenocarcinoma of the Esophagus

Factors with adequate evidence of increased risk of adenocarcinoma of the esophagus

Gastroesophageal reflux/Barrett esophagus

Based on fair evidence, an association exists between GERD and adenocarcinoma, particularly if the GERD is long-standing and symptoms are severe.[6,7] In a case-control study from Sweden, the OR for patients with recurrent reflux symptoms was 7.7, while the OR for patients with long-standing and severe symptoms was 43.5 (95% CI, 18.3–103.5).[8]

It is unknown whether elimination of gastroesophageal reflux by surgical or medical means will reduce the risk of adenocarcinoma of the esophagus.[8,9]

Magnitude of Effect: Unknown.

Study Design: Ecologic and descriptive studies.
Internal Validity: Fair.
Consistency: Good; multiple studies.
External Validity: Fair.

Interventions with adequate evidence of decreased risk adenocarcinoma of the esophagus

Aspirin and NSAID use

Benefits

Based on fair evidence, epidemiologic studies have found that aspirin or NSAID use is associated with decreased risk of developing or dying from esophageal cancer (OR, 0.57; 95% CI, 0.47–0.71).[5,10]

Magnitude of Effect: Positive; unknown magnitude.

Study Design: Evidence obtained from cohort or case-control studies.
Internal Validity: Fair.
Consistency: Good.
External Validity: Fair.

Harms

Magnitude of Effect: Increased risk; small magnitude.

Study Design: Evidence obtained from randomized controlled trials.
Internal Validity: Good.
Consistency: Good.
External Validity: Good.

Ablation of Barrett esophagus with dysplasia

Benefits

A randomized controlled trial has found that radiofrequency ablation of Barrett esophagus with severe dysplasia may lead to eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression.[11]

Magnitude of Effect: : Impact on cancer mortality not known.

Study Design: Evidence obtained from a randomized controlled trial.
Internal Validity: Good.
Consistency: Single study.
External Validity: Good.

Harms

Based on solid evidence, harms of radiofrequency ablation include esophageal stricture and requirement for dilatation and upper gastrointestinal hemorrhage but at low rates. It is possible that overdiagnosis and overtreatment of Barrett esophagus, particularly without severe dysplasia, could lead to a substantial number of harms.

Magnitude of Effect: The low rates of esophageal stricture and requirement for dilatation and upper gastrointestinal hemorrhage may be an understatement of the risks if this practice is widely adopted by less-experienced physicians.

Study Design: Evidence obtained from a randomized controlled trial.
Internal Validity: Good.
Consistency: Single study.
External Validity: Patients representative of a subset of people with dysplasia, particularly severe dysplasia; physicians may not be representative of practicing physicians because this is a new technology and requires specialized knowledge.

References

Engel LS, Chow WH, Vaughan TL, et al.: Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst 95 (18): 1404-13, 2003. [PUBMED Abstract]
Lagergren J: Controversies surrounding body mass, reflux, and risk of oesophageal adenocarcinoma. Lancet Oncol 7 (4): 347-9, 2006. [PUBMED Abstract]
Lagergren J, Bergström R, Adami HO, et al.: Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma. Ann Intern Med 133 (3): 165-75, 2000. [PUBMED Abstract]
Siemiatycki J, Krewski D, Franco E, et al.: Associations between cigarette smoking and each of 21 types of cancer: a multi-site case-control study. Int J Epidemiol 24 (3): 504-14, 1995. [PUBMED Abstract]
Corley DA, Kerlikowske K, Verma R, et al.: Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124 (1): 47-56, 2003. [PUBMED Abstract]
Lagergren J, Bergström R, Lindgren A, et al.: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340 (11): 825-31, 1999. [PUBMED Abstract]
Fitzgerald RC: Molecular basis of Barrett's oesophagus and oesophageal adenocarcinoma. Gut 55 (12): 1810-20, 2006. [PUBMED Abstract]
Lagergren J, Ye W, Lagergren P, et al.: The risk of esophageal adenocarcinoma after antireflux surgery. Gastroenterology 138 (4): 1297-301, 2010. [PUBMED Abstract]
Spechler SJ, Goyal RK: The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology 110 (2): 614-21, 1996. [PUBMED Abstract]
Liao LM, Vaughan TL, Corley DA, et al.: Nonsteroidal anti-inflammatory drug use reduces risk of adenocarcinomas of the esophagus and esophagogastric junction in a pooled analysis. Gastroenterology 142 (3): 442-452.e5; quiz e22-3, 2012. [PUBMED Abstract]
Shaheen NJ, Sharma P, Overholt BF, et al.: Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med 360 (22): 2277-88, 2009. [PUBMED Abstract]