Esophageal Cancer

Esophageal cancer is 1 of the most common causes of cancer-related deaths worldwide. Nearly all esophageal cancers are either adenocarcinoma (commonly affecting the distal esophagus) or squamous cell carcinoma (affecting the proximal two-thirds of the esophagus). Major risk factors for adenocarcinoma include smoking, obesity, and Barrett’s esophagus. For squamous cell carcinoma, risk factors include smoking, alcohol consumption, and certain dietary factors. Early-stage cancer is often asymptomatic, with dysphagia and weight loss presenting as the disease progresses. Diagnosis is by endoscopic biopsy or image-guided biopsy of the metastatic site. Management depends on the disease stage. Options include surgical resection, chemotherapy, and radiation. For unresectable esophageal cancers, palliative measures are provided for symptom relief and to prolong survival.

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Epidemiology and Etiology


  • 8th-most common cancer worldwide and 6th-most common cause of cancer-related deaths
  • Risk increases with age, especially during the 6th to 7th decades of life
  • Males > females
  • Majority of cases fall under 2 types:
    • Adenocarcinoma (AC)
      • Most common form in the United States
      • Higher incidence in Caucasians
    • Squamous cell carcinoma (SCC)
      • Most common form worldwide
      • 90% of esophageal cancers occur in the “esophageal cancer belt” (northern Iran, northern China, Central Asia, and southern Russia)
      • Incidence decreasing in the United States
      • Higher incidence in African Americans and Asians


  • Risk factors for adenocarcinoma:
    • Barrett’s esophagus secondary to gastroesophageal reflux disease (GERD)
    • Obesity
    • Smoking
  • Risk factors for squamous cell carcinoma (SCC):
    • Smoking
    • Alcohol intake
    • Diet low in vegetables and fruits
    • Achalasia
    • Caustic injuries
    • Human papillomavirus infection
    • Atrophic gastritis
    • Tylosis (Howel-Evans syndrome): autosomal dominant disease with hyperkeratosis of palm and sole 
    • Plummer-Vinson syndrome
    • Poor oral hygiene
    • Nitrosamine exposure (e.g., cured meats)
    • Drinking scalding-hot liquids
    • Areca nut or betel quid chewing
Table: Epidemiology of and risk factors for esophageal cancer
AdenocarcinomaSquamous cell carcinoma
RaceCaucasiansAfrican Americans, Asians
Major risk factorsBarrett’s esophagus, smoking, obesitySmoking, alcohol consumption, low vegetable and fruit intake, drinking hot liquids, caustic strictures, achalasia

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Clinical Presentation and Complications

Clinical presentation

  • Asymptomatic in early stages 
  • Signs and symptoms:
    • Progressive dysphagia (from solids to liquids):
      • Due to obstruction by the tumor
      • Noted when esophageal lumen is < 13 mm
    • Weight loss (from dysphagia and tumor-related anorexia)
    • Odynophagia in 20% of patients
Table: Esophageal cancers—differences in presentation
AdenocarcinomaSquamous cell carcinoma
Location (major distinguishing factor)Distal ⅓ of esophagus Esophagogastric junction (EGJ)Proximal two-thirds of esophagus
Early lesions
  • Mucosal irregularities, ulcer, or nodule
  • Detected due to surveillance of Barrett’s esophagus
  • Subtle, may appear normal
  • Friable tissue, erythema, erosions, plaques, nodules
Advanced lesionsUlcerated or exophytic mass with obstructionInfiltrating or ulcerated mass, may be circumferential


  • Iron-deficiency anemia secondary to chronic gastrointestinal bleeding
  • Local tumor spread:
    • Cough (trachea)
    • Hoarseness and vocal paralysis (recurrent laryngeal nerve)
    • Tracheoesophageal fistulas (direct invasion through the esophageal wall and main stem bronchus)
  • Metastasis:
    • Compressive symptoms from lymph node metastasis (aortic, liver, lung, mediastinal)
    • SCC: usually intrathoracic
    • AC: usually intraabdominal



  • Initial work-up of dysphagia: 
    • Barium swallow study: asymmetric narrowing or intraluminal masses 
  • Upper endoscopy: 
    • Allows for direct visualization and biopsy of lesions
    • Early lesions: superficial plaques, nodules, ulceration, mucosal irregularities
    • Advanced lesions: strictures, masses, obstruction
  • Endoscopic biopsy with brush cytology or image-guided biopsy (for metastatic site):
    • Adenocarcinoma: 
      • Mucin-producing intestinal-type mucosa
      • Adjacent Barrett’s mucosa and high-grade dysplasia
    • SCC: 
      • Keratin pearls: clusters of neoplastic cells with circular keratinization
      • Individual cell keratinization and intercellular bridges

Evaluation for regional disease and metastasis

  • Endoscopic ultrasound (EUS):
    • Most accurate for locoregional staging
    • Visualizes local disease and tumor depth
    • Detects regional nodal involvement 
    • Allows for fine needle aspiration biopsy of lymph nodes
  • Bronchoscopy:
    • Indicated for thoracic esophageal tumor at or above the carina
    • Helps assess airway invasion
  • Laryngoscopy:
    • Indicated for cervical SCC
    • Determines presence of concomitant SCC of the head and neck
  • Chest and abdominal computed tomography (CT) and/or positron emission tomography (PET)
    • For detection of metastasis
    • Integrated fluorodeoxyglucose (FDG)-PET/CT available for occult metastasis


Tumor, node, metastasis (TNM) staging:

  • T: extent of tumor in the esophageal wall 
    • T1: mucosa (innermost layer) and submucosa
    • T2: muscularis propria
    • T3: adventitia (outermost layer)
    • T4: involves adjacent structures of the esophagus
  • N: regional lymph nodes involved
  • M: presence of distant metastasis
Esophageal cancer staging

Locoregional esophageal cancer staging: The cancer is seen as the lesion penetrating the esophageal wall. Illustration depicts the staging from T1 (mucosa and submucosa) to advanced disease, involving adjacent structures in T4 and the lymph nodes (N).

Image by Lecturio.

Management and Prognosis

Curative treatment options

  • Endoscopic mucosal resection: 
    • For early cancer (limited to mucosa) or high-grade dysplasia (HGD) in Barrett’s esophagus
    • Lesion with diameter ≤ 2 cm
    • < ⅓ of the circumference of the esophageal wall involved
  • Surgery:
    • Esophagectomy:
      • Lesion penetrating up to the submucosa (T1 with no regional lymph nodes, no metastasis)
      • In some centers, lesions penetrating up to muscularis propria (T2) can be resected.
    • Esophagectomy following neoadjuvant chemotherapy or followed by chemoradiotherapy:
      • For locally advanced tumors (T3) with or without nodal disease
      • Selected patients with T4 disease
    • Contraindication to surgery: 
      • Metastasis to other organs or extraregional lymph node spread
  • Chemoradiation:
    • Use of radiation therapy and chemotherapy 
    • For downstaging the tumor for later resection or as definitive treatment
    • 2–3 drug cytotoxic regimen used due to higher response rate

Palliative options

  • For advanced esophageal cancer (metastatic disease)
  • Goals:
    • Symptom palliation and comfort
    • Prolong survival 
  • Chemoradiation 
  • Assess for positive HER2 (human epidermal growth factor 2) status of adenocarcinoma: add trastuzumab, a monoclonal antibody targeting the HER2 receptor
  • Endoscopic procedures:
    • Dilation
    • Stenting
    • Laser ablation


  • Depends on the stage of disease
  • 50%80% of patients on presentation have locally advanced or metastatic esophageal cancer.
  • Low survival rate noted in patients with lymph node or distant metastasis 
  • Overexpression of HER2 receptor: associated with aggressive cancer growth and poor survival

Differential Diagnosis

  • Barrett’s esophagus: results from chronic gastroesophageal reflux disease (GERD) leading to replacement of esophageal squamous epithelium by gastric columnar epithelium. Barrett’s esophagus is a risk factor for esophageal adenocarcinoma. Surveillance is recommended to detect dysplasia or adenocarcinoma early enough to provide treatment.
  • Esophageal stricture: narrowing of the esophagus that can result from GERD, malignancies, and caustic ingestion. The condition presents with dysphagia to solids, progressing to liquids. Barium swallow study shows a narrowed luminal diameter. Upper endoscopy allows for biopsy and dilation when necessary.
  • Esophageal spasm: presents with dysphagia to solids and liquids but is associated with sudden onset of chest pain that is not exertion-related. There are 2 types of esophageal spasm: distal esophageal spasm and hypercontractile esophagus. Manometry shows characteristic esophageal contractions with normal relaxation of the esophagogastric junction. 
  • Achalasia: an esophageal motility disorder that develops from degeneration of the myenteric plexus. There is impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients present with dysphagia to solids and liquids along with regurgitation. Diagnosis is established by high-resolution manometry. 
  • Esophageal ring and web: thin structures that produce partial occlusion of the esophageal lumen. Plummer-Vinson syndrome consists of iron-deficiency anemia, dysphagia, and a cervical esophageal web. Schatzki’s ring is the most common type of esophageal ring. Patients present with dysphagia to solids. Diagnosis is by barium swallow study and upper endoscopy.


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