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Two histologic types account for the majority of malignant esophageal neoplasms: adenocarcinoma and squamous carcinoma. Adenocarcinomas typically start in the lower esophagus and squamous cell carcinoma can develop throughout the esophagus. The epidemiology of these types varies markedly.
Incidence and Mortality
Estimated new cases and deaths from esophageal cancer in the United States in 2016:
The incidence of esophageal cancer has risen in recent decades, coinciding with a shift in histologic type and primary tumor location. In the United States, squamous cell carcinoma has historically been more prevalent although the incidence of adenocarcinoma has risen dramatically in the last few decades in the United States and western Europe.[2,3] Worldwide, squamous cell carcinoma remains the predominant histology, however, adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and western Europe. The incidence of adenocarcinoma has increased most notably among white males. In the United States, the median age of patients who present with esophageal cancer is 67 years. The majority of adenocarcinomas are located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown.
The esophagus and stomach are part of the upper gastrointestinal (digestive) system.
The esophagus serves as a conduit to the gastrointestinal tract for food. The esophagus extends from the larynx to the stomach and lies in the posterior mediastinum within the thorax in close proximity to the lung pleura, peritoneum, pericardium, and diaphragm. As it travels into the abdominal cavity, the esophagus makes an abrupt turn and enters the stomach. The esophagus is the most muscular segment of the gastrointestinal system and is composed of inner circular and outer longitudinal muscle layers. The upper and lower esophagus are controlled by the sphincter function of the cricopharyngeus muscle and gastroesophageal sphincter, respectively. The esophagus has a rich network of lymphatic channels concentrated in the lamina propria and submucosa, which drains longitudinally along the submucosa.
Tumors of the esophagus are conventionally described in terms of distance of the upper border of the tumor to the incisors. When measured from the incisors via endoscopy, the esophagus extends approximately 30 to 40 cm. The esophagus is divided into four main segments:
Risk factors for squamous cell carcinoma of the esophagus include:
Risk factors associated with esophageal adenocarcinoma are less clear. Barrett esophagus is an exception and its presence is associated with an increased risk of developing adenocarcinoma of the esophagus. Chronic reflux is considered the predominant cause of Barrett metaplasia. The results of a population-based, case-controlled study from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively correlated with increased risk of esophageal adenocarcinoma.
(Refer to the PDQ summary on Esophageal Cancer Prevention for more information.)
Favorable prognostic factors include the following:
Patients with severe dysplasia in distal esophageal Barrett mucosa often have in situ or invasive cancer within the dysplastic area. After resection, these patients usually have excellent prognoses.
In most cases, esophageal cancer is a treatable disease, but it is rarely curable. The overall 5-year survival rate in patients amenable to definitive treatment ranges from 5% to 30%. The occasional patient with very early disease has a better chance of survival.
Other PDQ summaries containing information related to esophageal cancer include the following:
For information about gastrointestinal stromal tumors, which can occur in the esophagus and are usually benign, refer to the following summary:
For information about supportive care for patients with esophageal cancer, refer to the following summaries:
Adenocarcinomas, typically arising in Barrett esophagus, account for at least 50% of malignant lesions, and the incidence of this histology appears to be rising. Barrett esophagus contains glandular epithelium cephalad to the esophagogastric junction.
Three different types of glandular epithelium can be seen:
Fewer than 50% of esophageal cancers are squamous cell carcinomas.
Gastrointestinal stromal tumors can occur in the esophagus and are usually benign. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.)
One of the major difficulties in allocating and comparing treatment modalities for patients with esophageal cancer is the lack of precise preoperative staging. The stage determines whether the intent of the therapeutic approach will be curative or palliative.
Standard noninvasive staging modalities include the following:
The overall tumor depth staging accuracy of endoscopic ultrasound is 85% to 90%, compared with 50% to 80% for CT; the accuracy of regional nodal staging is 70% to 80% for endoscopic ultrasound and 50% to 70% for CT.[1,2]
One retrospective series reported a 93% sensitivity and 100% specificity of regional nodal staging with endoscopic ultrasound-guided fine-needle aspiration (FNA). Endoscopic ultrasound-guided FNA for lymph node staging is under prospective evaluation.
Thoracoscopy and laparoscopy have been used in esophageal cancer staging at some surgical centers.[4,5,6] An intergroup trial reported an increase in positive lymph node detection to 56% of 107 evaluable patients with the use of thoracoscopy/laparoscopy, from 41% (with the use of noninvasive staging tests, e.g., CT, magnetic resonance imaging, and endoscopic ultrasound), with no major complications or deaths.
Noninvasive PET scan using the radiolabeled glucose analog 18-F-fluorodeoxy-D-glucose (FDG) for preoperative staging of esophageal cancer is more sensitive than a CT scan or endoscopic ultrasound in detection of distant metastases. A recent study of 262 patients with potentially resectable esophageal cancer demonstrated the utility of FDG-PET in identifying confirmed distant metastatic disease in at least 4.8% of patients after standard evaluation.[8,9,10,11,12]
AJCC Staging System
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define cancer of the esophagus and esophagogastric junction. Tumors located in the gastric cardia within 5 cm of the gastroesophageal junction with extension into the esophagus or the gastroesophageal junction are classified as esophageal cancer. Tumors with the epicenter of the tumor located in the gastric cardia beyond 5 cm of the gastroesophageal junction or without extension into the esophagus are classified as gastric cancer. (Refer to the Stage Information section in the PDQ summary on Gastric Cancer Treatment for more information.)
In contrast to earlier classification systems, the 2010 AJCC TNM staging system differentiates by histologic subtype, with an individualized staging system for squamous cell carcinoma versus adenocarcinoma, reflecting differences in inherent biology.
The classification of involved abdominal lymph nodes as M1 disease is controversial. The presence of positive abdominal lymph nodes does not appear to have a prognosis as grave as that for metastases to distant organs. Patients with regional and/or celiac axis lymphadenopathy should not necessarily be considered to have unresectable disease caused by metastases. Complete resection of the primary tumor and appropriate lymphadenectomy should be attempted when possible.
Staging for squamous cell carcinoma of the esophagus
Staging for adenocarcinoma of the esophagus
For patients with minimally invasive resectable esophageal cancer, surgical resection alone offers the potential for cure. In contrast, therapeutic management for patients with locally advanced resectable esophageal cancer has evolved significantly over the last few decades. Because of the risk of distant metastases and local relapse, multimodality therapy with integration of chemotherapy, radiation therapy, and surgical resection has become the standard of care.
Combined modality therapies are under clinical evaluation and include the following:
Effective palliation may be obtained in individual cases with various combinations of the following:
Surgery (Barrett esophagus)
The prevalence of Barrett metaplasia in adenocarcinoma of the esophagus suggests that Barrett esophagus is a premalignant condition. Endoscopic surveillance of patients with Barrett metaplasia may detect adenocarcinoma at an earlier stage that is more amenable to curative resection. Strong consideration should be given to resection in patients with high-grade dysplasia in the setting of Barrett metaplasia.
Surgery (esophageal cancer)
The survival rate of patients with esophageal cancer is poor. Surgical treatment of resectable esophageal cancers results in 5-year survival rates of 5% to 30%, with higher survival rates in patients with early-stage cancers. Asymptomatic small tumors confined to the esophageal mucosa or submucosa are detected only by chance. Surgery is the treatment of choice for these small tumors. Once symptoms are present (e.g., dysphagia, in most cases), esophageal cancers have usually invaded the muscularis propria or beyond and may have metastasized to lymph nodes or other organs.
In some patients with partial esophageal obstruction, dysphagia may be relieved by placement of an expandable metallic stent  or by radiation therapy if the patient has disseminated disease or is not a candidate for surgery. Alternative methods of relieving dysphagia have been reported, including laser therapy and electrocoagulation to destroy intraluminal tumor.[9,10,11]
In the presence of complete esophageal obstruction without clinical evidence of systemic metastasis, surgical excision of the tumor with mobilization of the stomach to replace the esophagus has been the traditional means of relieving the dysphagia.
The optimal surgical approach for radical resection of esophageal cancer is not known. One approach advocates transhiatal esophagectomy with anastomosis of the stomach to the cervical esophagus. A second approach advocates abdominal mobilization of the stomach and transthoracic excision of the esophagus with anastomosis of the stomach to the upper thoracic esophagus or the cervical esophagus. One study concluded that transhiatal esophagectomy was associated with lower morbidity than was transthoracic esophagectomy with extended en bloc lymphadenectomy; however, median overall disease-free and quality-adjusted survival did not differ significantly. Similarly, no differences in long-term quality of life (QOL) using validated QOL instruments have been reported. More recently, minimally invasive approaches that offer potential advantages of smaller incisions, decreased intraoperative blood loss, fewer postoperative complications, and shorter hospital stays have emerged. However, the ability to obtain negative surgical margins, the adequacy of lymph node dissection, and long-term outcomes have not been fully established with this approach.
In the United States, the median age of patients who present with esophageal cancer is 67 years. The results of a retrospective review of 505 consecutive patients who were operated on by a single surgical team over 17 years found no difference in the perioperative mortality, median survival, or palliative benefit of esophagectomy on dysphagia when the patients older than 70 years were compared with their younger peers.[Levels of evidence: 3iiA and 3iiB] All of the patients in this series were selected for surgery on the basis of potential operative risk. Age alone does not determine therapy for patients with potentially resectable disease.
Surgical treatment of esophageal cancer is associated with an operative mortality rate of less than 10%. In an attempt to avoid perioperative mortality and to relieve dysphagia, definitive radiation therapy in combination with chemotherapy has been studied.
Preoperative Chemoradiation Therapy
On the basis of several randomized trial results, chemoradiation followed by surgery is a standard treatment option for patients with stages IB, II, III, and IVA esophageal cancer.
Phase III trials have compared preoperative concurrent chemoradiation therapy with surgery alone for patients with esophageal cancer.[17,18,19,20,21,21,22,23][Level of evidence: 1iiA] The benefit of neoadjuvant chemoradiation has been controversial because of contradictory results of early randomized studies.[17,18,19,20] However, the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) has definitively demonstrated a survival benefit for preoperative chemoradiation compared with surgery alone in locally advanced esophageal cancer.
For early-stage tumors, the role of preoperative chemoradiation remains controversial. Although the CROSS study included early-stage patients, the Francophone de Cancérologie Digestive (FFCD) 9901 study (NCT00047112), which included only early-stage (stage I or II) patients, failed to demonstrate a survival advantage in this group of patients.
Evidence (preoperative chemoradiation therapy):
The effects of preoperative chemotherapy are being evaluated in randomized trials. Several studies have demonstrated a survival benefit with preoperative chemotherapy compared with surgery alone.[25,26,27] However, one large randomized study failed to confirm a survival benefit with preoperative chemotherapy. Compared with preoperative chemotherapy alone, preoperative chemoradiation therapy improves pathologic response and may improve outcomes.
Evidence (preoperative chemotherapy):
The interpretation of the results from the intergroup and preoperative chemotherapy trials is challenging because T or N staging was not reported, and prerandomization and radiation could be offered at the discretion of the treating oncologist.
For patients who are deemed either medically inoperable or have tumors that are unresectable, the efficacy of definitive chemoradiation has been established in numerous randomized controlled trials.[30,31] For patients with squamous cell carcinomas of the esophagus, definitive chemoradiation may offer equivalent outcomes compared with preoperative chemoradiation followed by surgical resection.[32,33]
Evidence (definitive chemoradiation):
Postoperative Radiation Therapy
Two randomized trials have shown no significant OS benefit for postoperative radiation therapy compared with surgery alone.[36,37][Level of evidence: 1iiA] All newly diagnosed patients should be considered candidates for therapies and clinical trials comparing various treatment modalities. Information about ongoing clinical trials is available from the NCI website.
Standard Treatment Options for Stage 0 Esophageal Cancer
Stage 0 squamous cell esophageal cancer is rarely seen in the United States, but surgery has been used.[1,2] For early-stage minimally invasive esophageal cancer, surgical and endoscopic techniques offer high rates of cure.[3,4]
Current Clinical Trials
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage 0 esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI website.
Standard Treatment Options for Stage I Esophageal Cancer
Standard treatment options for stage I esophageal cancer include the following:[1,2,3,4,5]
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage I esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Standard Treatment Options for Stage II Esophageal Cancer
Standard treatment options for stage II esophageal cancer include the following:
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage II esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Standard Treatment Options for Stage III Esophageal Cancer
Standard treatment options for stage III esophageal cancer include the following:
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage III esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Treatment Options for Stage IV Esophageal Cancer
At diagnosis, approximately 50% of patients with esophageal cancer will have metastatic disease and will be candidates for palliative therapy.
Treatment options for stage IV esophageal cancer include the following:
Treatment options under clinical evaluation:
Esophageal cancer responds to many anticancer agents. Objective response rates of 30% to 60% and median survivals of less than 1 year are commonly reported with platinum-based combination regimens with 5-FU, taxanes, topoisomerase inhibitors, hydroxyurea, or vinorelbine.[1,4,9] Trastuzumab may be effective in combination with chemotherapy among patients with tumors that overexpress HER2-neu.[Level of evidence: 1iiA]
Check the list of NCI-supported cancer clinical trials that are now accepting patients with stage IV esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Palliation presents difficult problems for all patients with recurrent esophageal cancer. All patients should be considered candidates for clinical trials as outlined in the Treatment Option Overview section of this summary.
Standard treatment options:
Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent esophageal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Esophageal Cancer
Updated statistics with estimated new cases and deaths for 2016 (cited American Cancer Society as reference 1).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about treatment of esophageal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Esophageal Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Esophageal Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/esophageal/hp/esophageal-treatment-pdq. Accessed <MM/DD/YYYY>.
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Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
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Last Revised: 2016-02-04
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