In Western countries, the diagnosis of esophageal cancer is generally made by endoscopic biopsy of the esophagus. In the Far East, cytologic evaluation is frequently used.
Endoscopic ultrasonography (EUS) is extremely accurate (> 90%) in establishing the depth of tumor invasion (T stage) but less accurate (70% to 80%) in determining nodal involvement (N stage) unless combined with fine-needle aspiration (FNA) of the involved nodes (93% accuracy) when nodes greater than 5 mm are biopsied. The addition of FNA increases the sensitivity from 63% to 93% and the specificity from 81% to 100%. EUS is not reliable in determining the extent of response to neoadjuvant treatment.
Endoscopy and Barium X-ray Films
Endoscopy allows for direct visualization of abnormalities and directed biopsies. Barium x-ray films are less invasive and provide a good assessment of the extent of esophageal disease.
Bronchoscopy should be performed to detect tracheal invasion in all cases of esophageal cancer except adenocarcinoma of the distal third of the esophagus.
Once a diagnosis has been established and careful physical examination and routine blood tests have been performed, a CT scan of the chest, abdomen, and pelvis should be obtained to help assess tumor extent, nodal involvement, and metastatic disease.
Positron Emission Tomography
A prospective trial designed to evaluate the utility of positron emission tomography (PET) vs CT and EUS was performed by obtaining these studies in 48 consecutive patients prior to esophagectomy. PET achieved a 57% sensitivity, a 97% specificity, and an 86% accuracy compared with CT, which was 99% sensitive, 18% specific, and 78% accurate. In terms of nodal staging, PET was correct in 83% of cases, compared with 60% of cases for CT and 58% for EUS (P = .006). This analysis suggests the improved accuracy of PET in the staging workup of patients with esophageal cancer.
Numerous studies report the accuracy of PET scanning in determining the presence of metastatic disease, with sensitivity approaching 90% and specificity over 90%.
As PET becomes more widely available, its use will probably become an important part of the preoperative evaluation of these patients. In a prospective trial of 39 patients with esophageal cancer, PET detected additional sites of metastatic disease at the initial evaluation when compared with conventional imaging. After induction therapy, PET did not add to the estimation of locoregional resectability and did not detect new distant metastases. However, this study suggested that changes in 18fluorodeoxyglucose (FDG)-PET following induction therapy may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. A large prospective national trial will evaluate the use of PET in the treatment of esophageal cancer, coordinated by the Cancer and Leukemia Group B (CALGB), clinicaltrials.gov number NCT01333033.
A bone scan should be obtained if the patient has bone pain or an elevated alkaline phosphatase level.
Investigators have begun to examine the role of surgical staging prior to definitive therapy. These procedures are designed to allow pathologic review of regional lymph nodes and the accurate assessment of extraesophageal tumor spread by direct visualization. A multi-institution trial (CALGB 9380) found these procedures to be feasible in more than 70% of patients; they resulted in the upstaging of patients in 38% of cases reviewed. Further investigations need to be completed to determine the appropriate use of these tools in treatment algorithms for patients with esophageal cancer.
Staging studies should be performed in a sequential manner. Invasive, lower-yield, and less accurate studies and procedures should only be undertaken if management would change on the basis of specific findings.
The role of screening patients with GERD and surveillance of patients with Barrett's esophagus by upper gastrointestinal endoscopy remains under investigation. In 833 patients studied by endoscopy, there was a 13% incidence of intestinal metaplasia (Barrett's esophagus). Dysplasia or cancer was seen in 31% of patients with long-segment Barrett's esophagus, in 10% with short-segment Barrett's esophagus, and in 6% with GE junction intestinal metaplasia.
Squamous cell carcinoma
Mass screening in the high-risk areas of China and Japan is considered appropriate and feasible.
The potential importance of the differences in histology on disease prognosis, and therefore treatment, which has been clinically recognized for several years, has resulted in differences in staging, based on histology in the seventh edition of the AJCC Cancer Staging Manual.
The incidence of esophageal adenocarcinoma involving the GE junction has risen 4% to 10% per year since 1976 in the United States and Europe. As a result, adenocarcinoma is now the predominant histologic subtype of esophageal cancer. The distal one-third of the esophagus is the site of origin of most adenocarcinomas.
Squamous Cell Carcinomas
Squamous cell carcinomas occur most often in the proximal two-thirds of the esophagus. Squamous cell carcinoma is still the most prevalent histologic subtype worldwide.
Other Tumor Types
Other, less frequently seen histologic subtypes include mucoepidermoid carcinoma, small-cell carcinoma, sarcoma, adenoid cystic leiomyosarcoma, and primary lymphoma of the esophagus. Occasionally, metastatic disease from another site may present as a mass in the esophagus or a mass pressing on the esophagus.
The most common sites of metastatic disease are the regional lymph nodes, lungs, liver, bone, adrenal glands, and diaphragm. Adenocarcinoma can also metastasize to the brain.
On the basis of data demonstrating that the depth of penetration has important prognostic significance, the American Joint Committee on Cancer (AJCC) TNM staging system for esophageal cancer was changed from a clinical one (1983) to a pathologic one in 2002. The seventh edition of the AJCC Cancer Staging Manual became available in January 2010, and staging updates for esophageal cancer are listed in Table 1. Both the clinical and pathologic staging systems are shown in this table, because patients may be cured without an operation. Although pathologic information obtained from an esophagectomy specimen is of prognostic importance, postoperative therapy to improve prognosis has not been rigorously tested. Moreover, recurrence rates for stages I (30%) and II (70%) cancers suggest early systemic spread undetected by current noninvasive staging.
Pathologic information obtained from an esophagectomy specimen is of significant prognostic importance. Immunohistochemical analysis of the initial biopsy specimen may also have prognostic relevance. Clinical staging has been shown to be of prognostic importance, particularly in patients managed with primary radiotherapy or chemoradiation therapy.
Histology and Grade
Neither histology nor grade has been shown to be of prognostic importance in esophageal carcinoma.
Other Prognostic Factors
Patient age, performance status, and degree of weight loss are of prognostic importance. The prognostic implications of tumor-suppressor genes and oncogenes are an area of active investigation.