Esophageal cancer

Last updated: November 17, 2023

Summarytoggle arrow icon

Esophageal cancer (EC) is the eighth most common type of cancer worldwide and affects men more than women (3:1 ratio). The two main forms are esophageal adenocarcinoma and squamous cell carcinoma. Esophageal adenocarcinomas are among the neoplasms with the fastest increasing incidence in northern and western Europe and North America, while squamous cell carcinoma is the most common form worldwide. Adenocarcinoma, which usually affects the lower third of the esophagus, may be preceded by gastroesophageal reflux disease and Barrett esophagus. Other risk factors include smoking and obesity. Risk factors for squamous cell carcinoma include carcinogen exposure (e.g., in the form of alcohol and tobacco) and a diet high in nitrosamines but low in fruits and vegetables. Locally advanced disease is common at the time of diagnosis because EC is typically asymptomatic early in the disease course. Symptomatic patients may experience weight loss, dyspepsia, progressive dysphagia, cervical adenopathy, hoarseness or persistent cough, and signs of upper gastrointestinal bleeding, such as hematemesis, melena, or anemia. Esophagogastroduodenoscopy (EGD) is used to directly visualize the lesion and obtain a biopsy sample for histopathological confirmation. Staging of the tumor involves CT scan of the chest and abdomen, a PET scan, and often transesophageal endoscopic ultrasound (EUS). Curative surgical resection may be considered for locally invasive cancers, but EC is unresectable in approximately 60% of patients at the time of diagnosis. For patients with unresectable disease, treatment options include chemotherapy, radiation, and palliative stenting. Prognosis is generally poor because of the aggressive nature of EC and oftentimes late diagnosis.

Epidemiologytoggle arrow icon

  • Sex: > (3:1) [1]
  • Incidence: an estimated 20,640 new cases of esophageal cancer will be diagnosed in 2022 in the United States [1]
  • Median age of onset: : between 60 and 70 years of age
  • Adenocarcinoma: : most common type of esophageal cancer in the US [2]
  • Squamous cell carcinoma (SCC): most common type of esophageal cancer worldwide [3]

Adenocarcinoma is more common in the US of America.

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Adenocarcinoma [4]

The most important risk factors for esophageal adenocarcinoma are gastroesophageal reflux and associated Barrett esophagus.

Squamous cell carcinoma (SCC) [4][5]

The primary risk factors for squamous cell esophageal cancer are alcohol consumption, smoking, and dietary factors (e.g., diet low in fruits and vegetables).

Classificationtoggle arrow icon

Siewert classification of adenocarcinoma of the esophagogastric junction [10]

  • Based on the location of the tumor in relation to the Z line
  • Siewert type I and II tumors are managed as esophageal cancer. [11]
Overview of Siewert classification [11]
Type Localization Surgical approaches

Siewert type I

Siewert type II
  • Center of the tumor located from 1 cm above to 2 cm below the Z line
Siewert type III

Clinical featurestoggle arrow icon

Early stages [4]

  • Often asymptomatic
  • May manifest with dysphagia or retrosternal discomfort

Advanced stages [4]

Initially, esophageal cancer is often asymptomatic. It typically becomes symptomatic at advanced stages.

Diagnosticstoggle arrow icon

Esophagogastroduodenoscopy (EGD) with biopsy is the best initial and confirmatory test in patients with suspected esophageal cancer. [12][13]

EGD [14]

Barium swallow [12]

Staging investigations [12]

Consider the following studies in consultation with a multidisciplinary team.

Laboratory studies [4]

Stagestoggle arrow icon

Once the diagnosis is confirmed, EC should be staged to determine management. The American Joint Committee for Cancer (AJCC) TNM classification is currently the standard staging system used in clinical practice.

AJCC staging (8th Edition, 2017) [16]

Pathologytoggle arrow icon

Adenocarcinoma [17]

Squamous cell carcinoma [17]

Treatmenttoggle arrow icon

General principles

Surgical resection [18]

  • Endoscopic submucosal resection for mucosal lesions [19]
  • Subtotal or total esophagectomy
    • Indications: localized or resectable locally advanced disease
    • Options include: gastric pull-through procedure, colonic interposition

Chemoradiotherapy [18][20]

Other interventional therapy [13]

Complicationstoggle arrow icon

Cancer-associated complications

Treatment-associated complications

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

  • Prognosis is generally poor due to an aggressive course (due to an absent serosa in the esophageal wall) and typically late diagnosis. [12][25]
  • The Surveillance, Epidemiology, and End Results (SEER) database tracks survival rates for patients with EC in the United States.
Estimated survival of patients diagnosed with EC between 2012–2018 [26]
SEER stage 5-year relative survival rate
  • 47%
  • 26%
  • 6%
Combined (any stage)
  • 21%

Referencestoggle arrow icon

  1. Esophagus cancer - Key Statistics for Esophageal Cancer. Updated: March 20, 2020. Accessed: September 16, 2020.
  2. Patel N, Benipal B. Incidence of Esophageal Cancer in the United States from 2001-2015: A United States Cancer Statistics Analysis of 50 States. Cureus. 2018.doi: 10.7759/cureus.3709 . | Open in Read by QxMD
  3. Wang Q-L, Xie S-H, Wahlin K, Lagergren J. Global time trends in the incidence of esophageal squamous cell carcinoma. Clinical Epidemiology. 2018; Volume 10: p.717-728.doi: 10.2147/clep.s166078 . | Open in Read by QxMD
  4. Short MW, Burgers KG, Fry VT. Esophageal Cancer.. Am Fam Physician. 2017; 95 (1): p.22-28.
  5. Ribeiro U, Posner MC, Safatle-ribeiro AV, Reynolds JC. Risk factors for squamous cell carcinoma of the oesophagus. British Journal of Surgery . 1996; 83 (9): p.1174-85.
  6. Straif K, Weiland SK, Bungers M et al. Exposure to high concentrations of nitrosamines and cancer mortality among a cohort of rubber workers. Occupational and Environmental Medicine. 2000; 57 (3): p.180-187.doi: 10.1136/oem.57.3.180 . | Open in Read by QxMD
  7. Liyanage SS, Rahman B, Ridda I, et al. The Aetiological Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma: A Meta-Analysis. PLoS ONE. 2013; 8 (7): p.e69238.doi: 10.1371/journal.pone.0069238 . | Open in Read by QxMD
  8. Domingues-Ferreira M, Grumach AS, Duarte AJDS, De Moraes-Vasconcelos D. Esophageal cancer associated with chronic mucocutaneous candidiasis. Could chronic candidiasis lead to esophageal cancer?. Medical Mycology. 2008; 47 (2): p.201-205.doi: 10.1080/13693780802342545 . | Open in Read by QxMD
  9. Delsing CE, Bleeker-Rovers CP, van de Veerdonk FL, et al. Association of esophageal candidiasis and squamous cell carcinoma. Medical Mycology Case Reports. 2012; 1 (1): p.5-8.doi: 10.1016/j.mmcr.2012.02.003 . | Open in Read by QxMD
  10. Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998; 85 (11): p.1457-1459.doi: 10.1046/j.1365-2168.1998.00940.x . | Open in Read by QxMD
  11. Lin D, Khan U, Goetze TO, et al. Gastroesophageal Junction Adenocarcinoma: Is There an Optimal Management?. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting. 2019; 39: p.e88-e95.doi: 10.1200/EDBK_236827 . | Open in Read by QxMD
  12. Rice TW, Gress DM, Patil DT, Hofstetter WL, Kelsen DP, Blackstone EH. Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67 (4): p.304-317.doi: 10.3322/caac.21399 . | Open in Read by QxMD
  13. Varghese TK, Hofstetter WL, Rizk NP et al. The society of thoracic surgeons guidelines on the diagnosis and staging of patients with esophageal cancer. The Annals of Thoracic Surgery. 2013; 96 (1): p.346-56.doi: 10.1016/j.athoracsur.2013.02.069 . | Open in Read by QxMD
  14. Alsop BR, Sharma P. Esophageal Cancer. Gastroenterol Clin North Am. 2016; 45 (3): p.399-412.doi: 10.1016/j.gtc.2016.04.001 . | Open in Read by QxMD
  15. Wilkinson JM, Codipilly DC, Wilfahrt RP. Dysphagia: Evaluation and Collaborative Management. Am Fam Physician. 2021; 103 (2): p.97-106.
  16. Raptis CA, Goldstein A, Henry TS, et al. ACR Appropriateness Criteria® Staging and Follow-Up of Esophageal Cancer. J Am Coll Radiol. 2022; 19 (11): p.S462-S472.doi: 10.1016/j.jacr.2022.09.008 . | Open in Read by QxMD
  17. Jain S, Dhingra S. Pathology of esophageal cancer and Barrett’s esophagus. Annals of Cardiothoracic Surgery. 2017; 6 (2): p.99-109.doi: 10.21037/acs.2017.03.06 . | Open in Read by QxMD
  18. Shah MA, Kennedy EB, Catenacci DV, et al. Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline. J Clin Oncol. 2020; 38 (23): p.2677-2694.doi: 10.1200/jco.20.00866 . | Open in Read by QxMD
  19. Evans JA, Early DS, Chandraskhara V, et al. The role of endoscopy in the assessment and treatment of esophageal cancer. Gastrointest Endosc. 2013; 77 (3): p.328-334.doi: 10.1016/j.gie.2012.10.001 . | Open in Read by QxMD
  20. Shah MA. Update on Metastatic Gastric and Esophageal Cancers. J Clin Oncol. 2015; 33 (16): p.1760-1769.doi: 10.1200/jco.2014.60.1799 . | Open in Read by QxMD
  21. Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021; 398 (10302): p.759-771.doi: 10.1016/s0140-6736(21)01234-4 . | Open in Read by QxMD
  22. Doki Y, Ajani JA, Kato K, et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022; 386 (5): p.449-462.doi: 10.1056/nejmoa2111380 . | Open in Read by QxMD
  23. Shah MA, Hofstetter WL, Kennedy EB. Immunotherapy in Patients With Locally Advanced Esophageal Carcinoma: ASCO Treatment of Locally Advanced Esophageal Carcinoma Guideline Rapid Recommendation Update. J Clin Oncol. 2021; 39 (28): p.3182-3184.doi: 10.1200/jco.21.01831 . | Open in Read by QxMD
  24. Ahmed O, Lee JH, Thompson CC, Faulx A. AGA Clinical Practice Update on the Optimal Management of the Malignant Alimentary Tract Obstruction: Expert Review. Clin Gastroenterol Hepatol. 2021; 19 (9): p.1780-1788.doi: 10.1016/j.cgh.2021.03.046 . | Open in Read by QxMD
  25. Berry MF. Esophageal cancer: staging system and guidelines for staging and treatment. Journal of Thoracic Disease. 2014; 6 (Suppl 3): p.S289-97.
  26. Survival Rates for Esophageal Cancer. Updated: March 1, 2022. Accessed: January 13, 2023.

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