Health Questions and Answers

Esophageal Cancer

What is the incidence of esophageal cancer in the United States, and is it changing?
Esophageal cancer is relatively infrequent in the United States. The annual incidence is <10 of 100,000 population, whereas in some areas of China the annual incidence is >100 of 100,000. Over the past three decades, the incidence of distal esophageal adenocarcinoma has increased sharply in North America, whereas the incidence of squamous cell carcinoma of the esophagus has fallen. The rise in esophageal adenocarcinoma has been most marked in white men. Recent studies suggest that the incidence of esophageal adenocarcinoma is rising in African-American and Hispanic men. For unknown reasons, the disease remains rare in women. Although the absolute numbers of cases of esophageal cancer remain low, there has been a remarkable rise in the incidence of distal esophageal cancer over the past three decades in most developed countries, making it one of the most rapidly growing cancers in the United States. The decline in distal gastric cancers over the same period has been correlated with a decline in the prevalence of Helicobacter pylori infection in the United States.

What are the risk factors for the development of esophageal cancer?
Smoking and alcohol use have been associated with the development of squamous cell carcinoma of the esophagus, but they do not appear to be major risk factors for the development of esophageal adenocarcinoma. Squamous cell carcinoma is much more frequent in African Americans than in whites, whereas adenocarcinoma is much more frequent in whites. Frequent, long-standing heartburn is an important risk factor for the development of esophageal adenocarcinoma. In some studies, obesity has been shown to be an independent risk factor, and obese patients with reflux disease are at particularly high risk for the development of esophageal cancer. Recent studies have drawn an epidemiologic link between the widespread use of drugs that affect the lower esophageal sphincter and the increasing risk of esophageal cancer. A true cause-and-effect relationship has not been established. Diets low in fresh fruits and vegetables have also been associated with esophageal cancer.

What are the current recommendations for screening and surveillance of esophageal cancer in patients at risk?

  1. Screening. Currently, there is no acceptable screening method for esophageal cancer in the United States. Some economic models have suggested that a one-time screening endoscopy to identify Barrett’s esophagus may be cost-effective in patients with long-standing reflux esophagitis, but the assumptions for the risk of developing cancer in Barrett’s esophagus in the model may be too high. The American College of Gastroenterology guidelines suggest that patients with chronic GERD are most likely to have Barrett’s esophagus and should undergo endoscopy.
  2. Surveillance. Surveillance is recommended in patients with Barrett’s esophagus, and the grade of dysplasia determines the interval for surveillance. In patients with low-grade dysplasia as the highest grade after a 6-month follow-up endoscopy with concentrated biopsies in the area of dysplasia, annual endoscopy is recommended until there is no dysplasia. The finding of high-grade dysplasia requires a repeat endoscopy (after double-dose therapy with proton pump inhibitor). Special attention should be paid to any mucosal irregularity, and endoscopic mucosal resection should be considered. An intensive biopsy protocol should ideally be performed with a therapeutic endoscope and large-capacity biopsy forceps. An expert pathologist should confirm the interpretation of high-grade dysplasia. Focal high-grade dysplasia (less than five crypts) may be followed with a 3-month surveillance. Intervention should be considered in a patient with confirmed multifocal high-grade dysplasia. Surveillance endoscopy intervals are lengthening; when dysplasia is not found on two consecutive surveillance endoscopies, a 3-year interval for surveillance is recommended by the American College of Gastroenterology guidelines.

How is esophageal cancer diagnosed?
Endoscopy and biopsy are necessary for the diagnosis of esophageal cancer. Staging has become important in the management of patients with esophageal cancer. Staging helps determine the choice of treatment and is an important determinant of prognosis. Computed tomography (CT) of the chest and abdomen is the recommended initial test for staging.

Discuss the role of endoscopic ultrasound in the diagnosis and staging of esophageal cancer.
In patients who appear to have limited local disease on CT and no evidence of distant metastases, endoscopic ultrasound may be helpful in regional staging. Esophageal cancer is seen as a hypoechoic interruption of the layers of the esophagus. Endoscopic ultrasound is better than CT at staging the depth of insertion. This factor becomes important in deciding between different methods of curative therapy. For example, patients with cancer localized to the mucosa can be considered for mucosal resection, but deeper levels of invasion make this therapy inappropriate. Endoscopic ultrasound has better results in regional staging than the newest spiral CT scanners. Magnetic resonance imaging (MRI) has not been particularly helpful in imaging the depth of local invasion. Endoscopic ultrasound may also be helpful in the evaluation of mediastinal lymph nodes. Large nodes (>10 mm) that are uniformly hypoechoic are suspicious. Fine-needle aspiration under ultrasound guidance may help to establish lymph node involvement.

How is esophageal cancer staged? Why is staging important?
Esophageal cancer staging is performed according to the tumor-node-metastasis (TNM) classification. Accurate staging is important to establish prognosis and treatment approach. Treatment, as in all malignant disorders, is based on the risk of the therapy balanced against the likelihood of a good outcome. Patient preference and local expertise may also determine the choice of treatment. Rational choices can be based on the stage of esophageal cancer, as discussed in later text.

What curative therapies are available for esophageal cancer?
Treatment guidelines from the American College of Gastroenterology recommend stage-directed therapy. Treatment options are summarized by stage in the following text:

  1. Stages 0, I, IIA (early-stage disease). Patients with early-stage disease are generally treated with curative surgery alone. Endoscopic mucosectomy, using a suction cap fitted with a snare, may be curative in stages 0 and I. Experience with this modality is increasing in the United States, but controlled data are lacking. Other ablative therapies have also been used, including electrocautery, argon plasma coagulation, and photodynamic therapy. Chemotherapy and radiation are not used as adjuvants for early-stage disease. Surgical therapy consists of resection of the tumor with anastomosis of the stomach with the cervical esophagus (gastric pull-up) or interposition of the colon to reestablish gastrointestinal continuity. Results are better in hospitals that perform this surgery frequently and poorer in small hospitals that perform the surgery infrequently. Photodynamic therapy (discussed later) is an alternative to surgery in patients with high-grade dysplasia or early cancer, particularly if the patient is unwilling or unfit for surgery. A recent study showed promising results in patients with high-grade dysplasia and early cancer.
  2. Stages IIB, III (regionally advanced disease). The results of single-modality (surgery, chemotherapy, or radiation) therapy are limited. Less than 10% of patients are cured by surgery alone. The results of radiation and chemotherapy alone are also limited. A recent meta-analysis has shown that a multimodality approach consisting of chemotherapy and radiation followed by surgery (triple therapy) offers the best likelihood of cure. Triple therapy is aggressive and expensive and has a high side-effect rate. Patients who are in poor general condition may elect to have palliative therapy after balancing the low probability of cure against the morbidity of treatment.
  3. Stage IV (distant metastases). Distant metastases make esophageal cancer incurable; therapy is palliative. Radiation and chemotherapy are frequently used and may offer small increases in survival rates with the trade-off of systemic side effects. In patients with dysphagia, a number of palliative measures are possible but do not prolong survival.

What are the endoscopic methods for the palliation of esophageal cancer?
A number of endoscopic methods are available. Endoscopic dilation causes temporary relief of dysphagia and is not effective as long-term therapy. Expandable metal stents provide rapid palliation of dysphagia, but late complications can be a problem. Membrane-covered metal stents were developed to prevent the problems associated with tumor ingrowth and have been shown to be superior to uncovered stents. A number of tumor ablative therapies are also available. Injection of absolute alcohol into the tumor has been reported and is inexpensive. There is little control of the degree of necrosis, and tracking of the alcohol beyond the esophagus can cause perforation and chemical mediastinitis. Argon plasma therapy and Nd YAG laser can restore luminal patency by tumor ablation. Argon plasma coagulation is considerably less expensive than laser therapy and is equally effective. The principal disadvantage of these modalities is that they may require multiple treatments (and therefore multiple visits to the hospital), which is undesirable in patients who have a short time to live. Photodynamic therapy is a recent development in the treatment of esophageal cancer. A light-sensitive drug (Photofrin) is injected intravenously and selectively accumulates in the tumor tissue. Specially developed catheters are used to deliver light to the tumor and cause necrosis of the tumor. The procedure is relatively safe and generally well tolerated. Its principal disadvantages are cost, the development of cutaneous photosensitivity, and strictures in the esophagus. The procedure was recently approved by the Food and Drug Administration (FDA) and is an important alternative for patients who either do not wish to have surgery or are deemed poor risks for surgery.

What does the future hold for patients at risk for development of esophageal cancer?
The future of esophageal cancer lies in prevention. Symptoms develop late in the disease, and most patients are incurable at presentation. Because of the low absolute numbers of patients developing the disease, widespread screening programs in the general population are unlikely to be cost-effective. One-time endoscopic screening for Barrett’s esophagus has been proposed in patients with chronic reflux disease as a method for identifying patients at risk, but timing, cost-effectiveness, and efficacy remain unproven. A systematic review of patients taking aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) suggested that these agents may be protective against adenocarcinoma and squamous cell carcinoma. Chemoprevention of esophageal cancer with aspirin or cyclooxygenase-2 (COX-2) inhibitors is an exciting new dimension that is undergoing further study.

Last Updated: May 12, 2010
References
WEBSITES
http://www.cancer.gov/cancer_information/cancer_type/esophageal
http://www.nlm.nih.gov/medlineplus/ency/article/000283.htm
http://www.cancer.gov/cancertopics/pdq/treatment/esophageal

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