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Esophageal cancer

Last updated: April 11, 2021

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Esophageal cancer (EC) is the eighth most common type of cancer worldwide and affects predominantly male individuals (3:1). The two main forms are esophageal adenocarcinoma and squamous cell carcinoma. Adenocarcinomas are considered the fastest-growing neoplasms in Western countries, while squamous cell carcinoma is still most common in the resource-limited countries. Development of EC is associated with a number of risk factors. Adenocarcinoma, which usually affects the lower third of the esophagus, may be preceded by gastroesophageal reflux disease and associated Barrett esophagus. Other risk factors are smoking and obesity. Major known risk factors for squamous cell carcinoma include carcinogen exposure (e.g., in form of alcohol and tobacco) and a diet high in nitrosamines, but low in fruits and vegetables. Initially, EC is usually asymptomatic, so locally advanced disease is common at time of diagnosis. Weight loss and dyspepsia can precede the primary symptom progressive dysphagia. Late stages may be characterized by cervical adenopathy, hoarseness or persistent cough, and signs of upper gastrointestinal bleeding, such as hematemesis or melena. Esophagogastroduodenoscopy is used for direct visualization and allows biopsy of the lesion for histopathological confirmation. Staging of the tumor includes transesophageal endoscopic ultrasound, CT scans of chest and abdomen, and bronchoscopy. Curative surgical resection may be considered for locally invasive cancers, but in about 60% of patients EC is already unresectable at time of diagnosis. In those cases, treatment options includes chemotherapy, radiation, and palliative stenting. Prognosis is generally poor due to the aggressive nature of EC and oftentimes late diagnosis.

  • Sex: > (3:1) [1]
  • Incidence: an estimated 18,440 new cases of esophageal cancer will be diagnosed in 2020 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.

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).

Early stages [10]

  • Often asymptomatic
  • May manifest with swallowing difficulties or retrosternal discomfort

Advanced stages [10]

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

Esophagogastroduodenoscopy

Barium swallow

  • Overview
    • Sensitive, but does not allow confirmation or staging of a malignancy
    • Inferior to endoscopy
  • Indications
  • Findings: asymmetrical and irregular borders of the esophagus with characteristic stenosis and proximal dilatation (apple core lesion)

Staging [11]

Siewert classification of adenocarcinoma of the esophagogastric junction

  • This classification was proposed by Siewert and is applied in clinical practice.
  • Recent guidelines suggest that tumors located ≤ 2 cm below the z-line (i.e., Siewert types I and II) should be treated as esophageal cancer. [12]
Overview of Siewert classification
Type Localization Comments and surgical approaches

Siewert type I

  • Center of the tumor located 1–5 cm above the z-line (associated with Barrett mucosa)
Siewert type II
  • Center of the tumor located 1 cm above or 2 cm below the z-line
Siewert type III

pTNM staging for esophageal squamous cell carcinoma

pTNM staging for esophageal squamous cell carcinoma
Stage AJCC/UICC TNM Tissue invasion Lymph node metastases Distant metastasis
Curative intent
  • Stage 0
  • None
  • None
  • Stage IA
  • T1a, N0, M0
  • Stage IB
  • T1b, N0, M0
  • T1, N0, M0
  • T2, N0, M0
  • Muscularis propria
  • Stage IIA
  • T2, N0, M0
  • T3, N0, M0
  • Adventitia
  • T3, N0, M0
  • Stage IIB
  • T3, N0, M0
  • T3, N0, M0
  • T3, N0, M0
  • T1, N1, M0
Intermediate intent
  • Stage IIIA
  • T1, N2, M0
  • T2, N1, M0
  • Muscularis propria
  • Stage IIIB
  • T4a, N0–1, M0
  • T3, N1, M0
  • Adventitia
  • T2–3, N2, M0
  • Muscularis propria or adventitia
Palliative intent
  • Stage IVA
  • T4a, N2, M0
  • T4b, N0–2, M0
  • T1–4, N3, M0
  • Any structure
  • Stage IVB
  • T1–4, N0–3, M1
  • Any number
  • Yes

pTNM staging for esophageal adenocarcinoma

pTNM staging for esophageal adenocarcinoma
Stage AJCC/UICC TNM Tissue invasion Lymph node metastases Distant metastasis
Curative intent
  • Stage 0
  • None
  • None
  • Stage IA
  • T1a, N0, M0
  • Stage IB
  • T1b, N0, M0
  • Stage IC
  • T1, N0, M0
  • T2, N0, M0
  • Muscularis propria
  • Stage IIA
  • T2, N0, M0
  • Stage IIB
  • T1, N1, M0
  • T3, N0, M0
  • Adventitia
  • None
Intermediate intent
  • Stage IIIA
  • T1, N2, M0
  • T2, N1, M0
  • Muscularis propria
  • Stage IIIB
  • T4a, N0–1, M0
  • T3, N1, M0
  • Adventitia
  • T2–3, N2, M0
  • Muscularis propria or adventitia
Palliative intent
  • Stage IVA
  • T4a, N2, M0
  • T4b, N0–2, M0
  • T1–4, N3, M0
  • Any structure
  • T1–4, N0–3, M1
  • Any structure
  • Yes

Adenocarcinoma [13]

Squamous cell carcinoma [13]

Curative

Palliative

  • Indication: patients with advanced disease (majority of patients)
  • Methods

Cancer-associated complications

Treatment-associated complications

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

Prognosis is generally poor due to an aggressive course (due to an absent serosa in the esophageal wall) and typically late diagnosis. [11][16]

5-year survival rate of esophageal cancer [17]
SEER stage 5-year survival rate
Localized
  • 47%
Regional
  • 25%
Distant
  • 5%
Combined
  • 20%
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  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. Hemminki K, Li X, Sundquist J, Sundquist K. Cancer risks in Crohn disease patients. Annals of Oncology. 2008; 20 (3): p.574-580. doi: 10.1093/annonc/mdn595 . | Open in Read by QxMD
  11. 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
  12. 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
  13. 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
  14. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015; 47 (9): p.829-54. doi: 10.1055/s-0034-1392882 . | Open in Read by QxMD
  15. Maple JT, Abu Dayyeh BK, Chauhan SS, et al. Endoscopic submucosal dissection: Technology Status Evaluation Report . Gastrointestinal Endoscopy. 2015; 81 (6): p.1311-1325. doi: 10.1016/j.gie.2014.12.010 . | Open in Read by QxMD
  16. Berry MF. Esophageal cancer: staging system and guidelines for staging and treatment. Journal of Thoracic Disease. 2014; 6 (Suppl 3): p.S289-97.
  17. Survival Rates for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/detection-diagnosis-staging/survival-rates.html. Updated: March 20, 2020. Accessed: October 8, 2020.