Cancer of the Esophagus
Summary of Key Points
Classification
• Esophageal cancer is subdivided into the following four groups: epithelial tumors, metastatic tumors, lymphomas, and sarcomas.
• Cancers of epithelial origin, predominantly squamous cell and adenocarcinomas, are the most common, and other histologic types are rare.
• The appropriate categorization of gastroesophageal junction tumors has been controversial, and patients have been included in clinical trials directed both at esophageal and gastric cancers.
Incidence
• Within the United States, the incidence of esophageal cancer in persons younger than 80 years is 3.2 per 100,000 persons.
• Historically and internationally, squamous cell tumors are the most common histologic type; however, a dramatic increase in the incidence of adenocarcinoma has been documented in the United States, United Kingdom, and Western Europe.
Pathogenesis
• The data support the hypothesis that epithelial tumors arise as a result of chronic irritation from a wide variety of sources, including gastric contents in chronic reflux and known carcinogens.
• A strong association of Barrett esophagus and adenocarcinoma is seen, but a benefit to screening endoscopy for those at risk for or with known Barrett esophagus is unknown as the overall risk of cancer-related mortality is low. Studies with longer-term follow-up are needed to clarify this issue. Other identified risk factors are gastroesophageal reflux disease (GERD), obesity, and smoking.
• Squamous cell carcinoma is associated with smoking as well as alcohol use, and the declining incidence has paralleled the decline in smoking.
• Point mutations, increased copy number, and promotor region hypermethylation all appear important in the progression to malignancy.
Diagnosis and Staging
• Symptoms and demographics will strongly suggest the diagnosis.
• Endoscopy is the best screening examination but esophagram may also be used.
• Diagnosis is made by endoscopy with cytology and biopsy of tumor.
• Transesophageal ultrasound should be used to assess T and N stage to guide optimal definitive therapy.
• Computed tomography (CT) of chest and abdomen is useful in screening for metastatic disease.
• Positron emission tomographic (PET) scan is useful to detect additional cases of metastatic disease before costly and toxic definitive therapy. It may be superior to endoscopic ultrasound (EUS) in detecting intraabdominal lymph nodes, but not periesophageal nodes adjacent to the primary tumor.
• Additional studies include laparoscopy, thoracoscopy, bone scan, and CT of the brain when indicated by clinical circumstances.
• The new AJCC/UICC 7 staging system contains important changes: adenocarcinoma and squamous cell carcinoma are separate; grade of histology is incorporated; the gastroesophageal junction is defined; nodal staging is based on number of involved nodes, similar to gastric cancer; Tis includes high graded dysplasia; and T4 is subcategorized by features suggestive of resectability.
• Staging is based on pathological findings at the time of resection, but therapy is often guided by staging estimated by clinical testing.
Treatment
• Treatment of premalignant dysplasia is guided by grade of histology. Low-grade dysplasia should be closely followed by endoscopy. High-grade dysplasia is treated with endoscopic therapy or esophagectomy, although close follow-up may be appropriate for selected patients.
• Selection of appropriate treatment for carcinoma depends on tumor stage and patient performance status.
