Esophageal Cancer

Aka: Esophageal Cancer, Esophageal Carcinoma, Squamous Cell Carcinoma of the Esophagus, Esophageal Adenocarcinoma

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II. Epidemiology

  1. Incidence in U.S. (2016): 16,910 diagnosed (15,910 deaths)
  2. Worldwide, 8th most common cancer
    1. 80% of cases occur in non-industrialized countries (esp. Asia, Africa)

III. Types

  1. Squamous Cell Carcinoma of the Esophagus
    1. Accounts for 90% of cases worldwide, but much less common in the U.S.
      1. Incidence: 3 per 100,000 person-years in U.S,
      2. Most common in China, Central Asia, East Africa, South Africa
    2. Typical: 60 to 70 year old black male
      1. Black patients predominate by 3 fold (compared with white patients)
    3. Conditions predisposing to cancer development
      1. Tobacco Smoking (RR 9)
      2. Alcohol Abuse (RR 2-3 if >=3 drinks/day)
      3. Diet low in vegetables and fruits (high starch diet)
      4. Achalasia (RR 10)
      5. Plummer-Vinson surgery
      6. Other head and neck surgery or radiation
  2. Adenocarcinoma of the Esophagus
    1. Most common cause in U.S.
    2. Incidence at age 65 years: 11.8 to 16.3 per 100,000 person-years (U.S.)
    3. Typical: 50 to 60 year old white male
      1. Males predominate by 8 fold
      2. White patients predominate by 5 fold (compared with black patients)
    4. Conditions predisposing to cancer development
      1. Tobacco Abuse (RR 2)
      2. Obesity (RR 2-4)
      3. Barrett's Esophagus
      4. Gastroesophageal Reflux (RR 5-7)
      5. Hiatal Hernia
      6. Scleroderma
      7. Zollinger-Ellison syndrome
      8. Achalasia history with status-post myotomy
  3. Other rare types (<5% of total cases)
    1. Lymphoma, Sarcoma, Melanoma and Carcinoid Tumors involving the Esophagus

IV. Symptoms

  1. Initial
    1. Asymptomatic
  2. Presentation (most common Esophageal Cancer presentations)
    1. Progressive symptoms on Swallowing for months
      1. Progressive solid Dysphagia to liquid Dysphagia
      2. Odynaphagia (painful Swallowing, esp with dry foods)
    2. Unintentional Weight Loss (10% over <3-6 months)
  3. Later
    1. Dyspepsia
    2. Heartburn
    3. Trunk pain
      1. Initially Swallowing-induced (constant later)
      2. Location of pain
        1. Chest and upper back: Upper 2/3 of Esophagus
        2. Abdomen and low back: Lower third of Esophagus
    4. Other symptoms or signs
      1. Halitosis
      2. Digital Clubbing
      3. Hematemesis or Hemoptysis

V. Signs: Suggesting local tumor spread

  1. Hoarseness (Recurrent laryngeal nerve involvment, 10% of patients)
  2. Horner Syndrome
  3. Cervical Lymphadenopathy
  4. Peristent Hiccups (diaphragm association)

VI. Diagnosis

  1. Upper Endoscopy with stains (chromoendoscopy), color filters, biopsies and brushings (see evaluation below)
  2. Endoscopic Ultrasound for invasive disease (see evaluation)
    1. Indicated if no distant metastases
    2. Identifies tumor depth and and nodal involvement
    3. May also guide fine needle biopsy
    4. Efficacy in identifying tumor invasion
      1. Test Sensitivity: 82-87%
      2. Test Specificity: 73-78%

VII. Labs

  1. Complete Blood Count (CBC)
    1. Anemia
  2. Liver Transaminases (AST, ALT)
    1. Increased with liver metastases
  3. Alkaline Phosphatase
    1. Increased with bone metastases
  4. Other labs per oncology
    1. HER2/neu overexpression
      1. Determine if Trastuzumab (Herceptin) candidate in those with metastatic esophageal junction cancer

VIII. Imaging: Evaluate Involvement and Differential Diagnosis

  1. CT Chest, Abdomen and Pelvis
    1. Performed with intravenous and Oral Contrast
    2. More sensitive than PET for evaluating local regional lesions
  2. Positron Emission Tomography (PET)
    1. Perform with CT if Esophageal Cancer is confirmed
    2. More sensitive than CT for identifying distant metastases
  3. Imaging Efficacy for identifying metastases (Integrated PET-CT)
    1. Test Sensitivity: 69-78%
    2. Test Specificity: 82-88%

IX. Evaluation

  1. Step 1: Upper endoscopy with stains (chromoendoscopy), color filters, biopsies and brushings
    1. If cancer present, go to step 2a
    2. Otherwise treatment based on findings
      1. Gastroesophageal Reflux
      2. Barrett's Esophagus
  2. Step 2a: Evaluate for metastases
    1. CT Chest, Abdomen and Pelvis with intravenous and Oral Contrast
    2. Positron Emission Tomography (PET) in combination with CT is preferred
    3. Labs (see above)
  3. Step 2b: Are distant metastases present?
    1. No distant metastases: Step 4a
    2. Distant Metastases
      1. Palliative measures (see management below)
  4. Step 3a: Obtain Endoscopic Ultrasound
    1. No Lymphovascular Invasion: Go to Step 4
    2. Lymphovascular Invasion
      1. Perform fine needle aspirate (FNA) of lesions during endoscopic Ultrasound
  5. Step 4: No Lymphovascular Invasion on Endoscopic Ultrasound
    1. Lesion <2 cm and limited to mucosa or lamina propria (Tis or T1a)
      1. Endoscopic mucosa resection
    2. Lesion >= 2 cm or submucosal invasion (T1b, T2, T3)
      1. Esophagectomy with Lymphadenectomy

X. Staging: AJCC Cancer Staging TNM

  1. Primary Tumor (T)
    1. Tis: High grade dysplasia
    2. T1a: Invades lamina propria
    3. T1b: Invades submucosa
    4. T2: Invades muscularis propria
    5. T3: Invades adventitia
    6. T4a: Invades nearby structures and is resectable (e.g. pleura, Pericardium, diaphragm)
    7. T4b: Invades nearby structures and is not resectable (e.g. aorta, Vertebrae, trachea)
  2. Regional Lymph Nodes (N)
    1. N0: No regional Lymph Node involvement
    2. N1: 1-2 positive regional Lymph Nodes
    3. N2: 3-6 positive regional Lymph Nodes
    4. N3: >6 positive regional Lymph Nodes
  3. Distant Metastases (M)
    1. M0: No distant metastases
    2. M1: Distant Metastases
  4. Stages
    1. Stage 0: Carcinoma in-situ
    2. Stage I: (T1-N0-M0)
      1. Tumor invades to lamina propria or submucosa
    3. Stage IIA: (T2-N0-M0) through (T3-N0-M0)
      1. Tumor invades to muscularis propria or adventitia
    4. Stage IIB: (T1-N1-M0) or (T1-N1-M0)
      1. Regional Lymph Node spread
    5. Stage III: (T3-N1-M0) or (T4-N1-M0)
      1. Local invasion to at least adventitia and
      2. Regional Lymph Node spread
    6. Stage IV (M1)
      1. Distant Metastases
  5. References
    1. Rice (2010) Ann Surg Oncol 17(7): 1721-4 [PubMed]

XI. Grading

  1. G1: Well differentiated
  2. G2: Moderately differentiated
  3. G3: Poorly differentiated
  4. G4: Undifferentiated

XII. Management

  1. Localized Esophageal Cancer (41% five year survival)
    1. Stage 0-Ia (Tis-T1b N0 M0)
      1. Localized involvement lamina or submucosa (but no deeper)
        1. Lymphatic spread risk <2%
      2. Management
        1. Endoscopic mucosal resection (complelety resected in 91-98%)
    2. Stage Ib-IIa: (T2-N0-M0) through (T3-N0-M0)
      1. Tumor invades deeper than the submucosa, but no known Lymph Node involvement
        1. Still asssociated with a 20% risk of Lymph Node involvement
      2. Management
        1. Laparoscopic esophagectomy with lymphadenectomy
  2. Regional Esophageal Cancer (23% five year survival)
    1. Stage IIB to IIIC (Tany, N1-3, M0)
    2. Management
      1. Esophagectomy with lymphadenectomy
        1. High Risk Surgery (30-50% major complication rate, 5% mortality)
      2. Perioperative Chemotherapy or chemoradiotherapy (esp. Stage III, squamous cell cancer)
  3. Metastatic Esophageal Cancer - Stage IV (5% five year survival, accounts for 75% of cases at time of diagnosis)
    1. Management: Palliative measures for Stage IV
      1. Brachytherapy
      2. Esophageal dilation or Esophageal bypass
      3. Jejunostomy tube or Gastrostomy Tube
      4. Palliative Chemotherapy (esp. squamous cell cancer)
      5. Mucosal stents (self-expanding)
      6. Laser fulguration
      7. Trastuzumab (Herceptin)

XIII. Prevention

  1. General
    1. No strong evidence as of 2016 for high efficacy of any prevention strategy
    2. No asymptomatic screening
  2. Tobacco Cessation
  3. Decrease Alcohol and Caffeine
  4. Increase vegetables and fruits in diet
  5. Manage Achalasia and strictures
  6. Control Gastroesophageal Reflux

XIV. Prognosis

  1. Five year survival: 15-20% (in U.S. and in World)
  2. Five year survival in U.S.
    1. Localized Esophageal Cancer: 41%
    2. Regional Esophageal Cancer: 23%
    3. Metastatic Esophageal Cancer: 5%

XV. References

  1. Layke (2006) Am Fam Physician 73(12):2187-94 [PubMed]
  2. Rustgi (2014) N Engl J Med 371(26): 2499-509 [PubMed]
  3. Short (2017) Am Fam Physician 95(1): 22-8 [PubMed]
  4. Wang (2004) Curr Opin Gastroenterol 20:381-5 [PubMed]

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