Esophageal Cancer Overview

Epidemiology

• Esophageal Cancer
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• Incidence: 15,600 cases in US (2007 Estimate)
  • Incidence rate about 200-260 per 100,000
  • Higher incidence in men 4x (12.1k vs. 3.4k)
  • Higher incidence in African Americans by 5x
• Deaths: 13,900 deaths in US (2007 Estimate)
• Percentage and overall incidence of adenocarcinomas is increasing; increasing number of cancers involving the distal esophagus.
• 1/3 of H&N cancer patients who develop a second primary tumor will have esophageal cancer.
• Barrett's esophagus risk for developing adenoCa is significantly higher (14-150x) over general population, and corresponds ~0.5% per year. Progression is more likely with development of dysplasia within the metaplastic area, occurring in ~20% patients

• Leeds; 2007 (UK) PMID 17890521 -- "Risk of Mortality and Cancer Incidence in Barrett's Esophagus." (Cook MB, Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2090-6. Epub 2007 Sep 21.)
  • Retrospective. 502 patients with BE. Standardized mortality ratios (SMR) and standardized incidence rates (SIR) estimated
  • Outcome: Overall mortality elevated (SMR 1.21), even after excluding esophageal CA (1.16). Risk for esophageal CA mortality (SMR 7.3), digestive tract diseases (SMR 2.0)
  • Esophageal CA incidence rates: overall esophageal CA SIR 8.7, esophageal adenoCA 14.3
  • Conclusion: Increased risk of esophageal CA incidence (9x; for adeno 14x) and mortality (7x)

Risk Factors

• Tobacco
• Alcohol
• Fruits and vegetables - protective
• Socioeconomic status - low is worse, particularly in African American men
• Obesity - worse for adeno
• GERD - associated with development of Barrett's
• H. pylori - protective for adeno
• Barrett's esophagus - single most important risk factor for adeno
• Tylosis - autosomal dominant, tylosis esophageal cancer (TOC) gene, develop esophageal papillomas, and at extremely high risk of developing esophageal cancer
• Plummer-Vinson - approximately 10% develop hypopharynx or esophagus cancer
• Caustic injury
• Achalasia
• Prior aerodigestive tract malignancy

Anatomy

• Length is about 25 cm. Esophageal lesion distance on EGD is typically given from incisors
• Clinically important distance is from incisors to GEJ, which is ~40 cm.
• Layers:
  • Mucosa: epithelium, lamina propria, muscularis mucosa. Separated by basement membrane from rest of esophageal wall
  • Submucosa: fibroelastic fibers, nervous plexuses, glands
  • Muscularis propria: inner circular muscle layer, outer longitudinal muscle layer
  • Adventitia: dense periesophageal connective tissue
  • The serosa only lines the intra-abdominal esophagus
• AJCC divisions of the esophagus: (These are based on adjacent surgical landmarks)
  • Cervical esophagus:
    • Hypopharynx to the thoracic inlet, which is at the level of the sternal notch.
    • By endoscopy, 15 to <20 cm from the incisors
    • If thickening of the esophageal wall begins above the sternal notch, the location is cervical
  • Upper thoracic esophagus:
    • Thoracic inlet to lower border of the azygos vein
    • By endoscopy, 20 to <25 cm
  • Middle thoracic esophagus:
    • Lower border of the azygos vein to the inferior pulmonary veins
    • By endoscopy, 25 to <30 cm
  • Lower thoracic esophagus and EG junction:
    • Inferior pulmonary veins to the stomach; includes the intraabdominal portion of the esophagus
    • By endoscopy, 30 to 40 cm
    • For cancers arising near the EGJ, they are staged as esophageal/EGJ if the epicenter is in the lower thoracic esophagus, the EGJ, or within the proximal 5 cm of the stomach (cardia) and extend into the EGJ or esophagus
    • Those with an epicenter in the stomach greater than 5 cm distal the EGJ, or those within 5 cm of the EGJ but that do not extend into the EGJ or esophagus, are staged as gastric
    • Siewert classifaction is disregarded
• Historical divisions of the esophagus
  • Cervical esophagus - begins at cricopharyngeal muscle, 18 cm from the incisors (C7 level), to the thoracic inlet, 20-24 cm from incisors (T3 level).
  • Thoracic esophagus - from thoracic inlet, 24 cm from incisors (T3), to GE junction (usually T10 or T11).
    • Upper thoracic - T3 to T4, 20 cm to 25 cm - thoracic inlet to carina
    • Mid thoracic - T5 to T8, 25 cm to 35 cm - carina to inferior pulmonary vein
    • Lower thoracic - T9 to T10, 35 to 40 cm - below pulmonary vein
  • GE junction: (Classification by Siewert: PMID 11525305, PMID 9823902), center within 5 cm proximal/distal to GEJ
    • Type I (distal esophagus) - arises from area with specialized intestinal metaplasia of the esophagus. Commonly, center of the tumor located 1 - 5 cm above the gastroesophageal junction
    • Type II (cardia, considered gastric) - arises from the cardiac epithelium or short segments with intestinal metaplasia at the GEJ. Commonly, center of the tumor located 1 cm above to 2 cm distal to GEJ
    • Type III (sub-cardia, considered gastric) - arises from subcardial location and infiltrates GEJ from below. Commonly, center of tumor >2 cm distal to GEJ
• Resectability often limited:
  • Lack of fibrous serosa to prevent local spread
  • Rich lymphatic network in submucosa and muscularis that allows longitudinal and circumferential drainage
  • Frequent medical comorbidities

Barrett's Esophagus

• Multi-Institutional -- RFA vs. Sham procedure
  • Randomized, 2:1. 127 patients, dysplastic Barrett's esophagus. Arm 1) RFA vs. Arm 2) Sham procedure. Primary outcome 1-year rate of dysplasia/metaplasia
  • 2009 PMID 19474425 -- "Radiofrequency ablation in Barrett's esophagus with dysplasia." (Shaheen NJ, N Engl J Med. 2009 May 28;360(22):2277-88.)
    • Outcome: In low grade dysplasia patients: complete eradication RFA 90% vs. sham 23% (SS). In high grade dysplasia patients 81% vs. 19% (SS). Disease progression RFA 4% vs. sham 16% (SS), cancer development 1% vs. 9% (SS)
    • Toxicity: More chest pain, 1 patient UGI bleeding, 6% esophageal stricture
    • Conclusion: RFA associated with a high rate of complete eradication of dysplasia and intestinal metaplasia, and reduced risk of disease progression

Presentation

• 50% present with local or locoregional disease.
• Fewer than 60% of pts with locoregional disease are operable.

Patterns of spread

LN involvement risk is 20% for cervical tumors, 50% for mid thoracic, 30% for distal.

Extensive longitudinal interconnecting system of lymphatics.

• LN+ risk by location:
  • Cervical esophagus - 69% peritracheal & periesophageal. Only 6% supraclav, 9% abdominal LN.
  • Upper thoracic - 29% superior mediastinal nodes, 27% middle mediastinal nodes, 29% lower mediastinal nodes, 32% abdominal nodes
  • Middle thoracic - 11% superior mediastinal, 21% middle mediastinal, 18% lower mediastinal, 40% abdominal nodes
  • Lower thoracic - 10% superior mediastinal, 14% middle mediastinal, 27% lower mediastinal, 70% abdominal nodes
• LN+ risk by stage
  • T1a - 7%
  • T1b - 20%
  • T2 - 40%
• Overall distant metastasis rate 50%. Most commonly to the lung and liver.

• Southern Tohoku, Japan; 2009 (1989-2008) PMID 19042946 -- "Determination of the irradiation field for clinical T1-T3N0M0 thoracic/abdominal esophageal cancer based on the postoperative pathological results." (Nakamura T, Jpn J Clin Oncol. 2009 Feb;39(2):86-91. Epub 2008 Nov 28.)
  • Retrospective. 95 patients, clinical T1-T3N0 thoracic/abdominal esophageal cancer. Squamous cell 85%, adeno 9%. Rate of pathologic LN involvement evaluated
  • Outcome: Positive LN 42% (upper 37%, middle 32%, lower 46%, abdominal 70%).
  • Radiation fields: Extent of irradiation fields for each subsite determined
  • Conclusion: Lymph node mets seen often in cT1-T3; optimal fields designed

Prognosis

• No treatment: 6 month OS 20%, 5-year OS 0%
• Surgery alone: 5-year OS 20-25%
• Stage I: 5-year OS 80-90%
• Stage IIA (T2-T3 N0): 50%
• Stage IIB (T1-T2 N1): 20%
• Stage III (T3-T4 N1): 10-15%
• Stage IVa (M1a): 10%
• Palliation of dysphagia with surgery - 80%.

External Links

MCQs on Esophagus