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Esophageal Cancer Treatment (PDQ®)

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General Information About Esophageal Cancer
Cellular Classification of Esophageal Cancer
Stage Information for Esophageal Cancer
Treatment Option Overview for Esophageal Cancer
Stage 0 Esophageal Cancer
Stage I Esophageal Cancer
Stage II Esophageal Cancer
Stage III Esophageal Cancer
Stage IV Esophageal Cancer
Recurrent Esophageal Cancer
Changes to This Summary (02/04/2016)
About This PDQ Summary

General Information About Esophageal Cancer

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: [1]

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. [4] The incidence of adenocarcinoma has increased most notably among white males. [5] In the United States, the median age of patients who present with esophageal cancer is 67 years. [6] The majority of adenocarcinomas are located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown.

Anatomy

Gastrointestinal (digestive) system anatomy; drawing shows the esophagus, liver, stomach, small intestine, and large intestine.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:

  1. Cervical esophagus (~15–20 cm from the incisors).
  2. Upper thoracic esophagus (~20–25 cm from the incisors).
  3. Middle thoracic esophagus (~25–30 cm from the incisors).
  4. Lower thoracic esophagus and gastroesophageal junction (~30–40 cm from the incisors).

Risk Factors

Risk factors for squamous cell carcinoma of the esophagus include:

Risk factors associated with esophageal adenocarcinoma are less clear. [3] 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. [7]

(Refer to the PDQ summary on Esophageal Cancer Prevention for more information.)

Prognostic Factors

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. [8]

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.

Related Summaries

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:

References:

  1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 11, 2016.
  2. Brown LM, Devesa SS, Chow WH: Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst 100 (16): 1184-7, 2008.
  3. Blot WJ, McLaughlin JK: The changing epidemiology of esophageal cancer. Semin Oncol 26 (5 Suppl 15): 2-8, 1999.
  4. Schmassmann A, Oldendorf MG, Gebbers JO: Changing incidence of gastric and oesophageal cancer subtypes in central Switzerland between 1982 and 2007. Eur J Epidemiol 24 (10): 603-9, 2009.
  5. Kubo A, Corley DA: Marked multi-ethnic variation of esophageal and gastric cardia carcinomas within the United States. Am J Gastroenterol 99 (4): 582-8, 2004.
  6. Ginsberg RJ: Cancer treatment in the elderly. J Am Coll Surg 187 (4): 427-8, 1998.
  7. Lagergren J, Bergström R, Lindgren A, et al.: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340 (11): 825-31, 1999.
  8. Reed MF, Tolis G Jr, Edil BH, et al.: Surgical treatment of esophageal high-grade dysplasia. Ann Thorac Surg 79 (4): 1110-5; discussion 1110-5, 2005.

Cellular Classification of Esophageal Cancer

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.)

Stage Information for Esophageal Cancer

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.

Staging Evaluation

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. [3]

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. [7]

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. [13] 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. [13] (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. [13]

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. [14] 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

Table 1. Definitions of TNM Stage 0 Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescription
01, XAnyTis, N0, M0Tis = High-grade dysplasia.d
N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–d are at the end of Table 9.

Table 2. Definitions of TNM Stage IA Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IA1, XAnyT1, N0, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.

Stage IA squamous cell cancer of the esophagus; drawing shows the esophagus and stomach. An inset shows cancer cells in the mucosa and submucosa layers of the esophagus wall. Also shown are the muscle and connective tissue layers of the esophagus wall and lymph nodes.Stage IA squamous cell cancer of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall. The cancer cells are grade 1 or the grade is unknown. Grade 1 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 2-3 cancer cells.

N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 9.

Table 3. Definitions of TNM Stage IB Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IB2–3AnyT1, N0, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.

Stage IB squamous cell cancer of the esophagus; drawing shows the  esophagus and stomach. A two-panel inset shows the layers of the esophagus wall: the mucosa, submucosa, muscle, and connective tissue layers. Also shown are lymph nodes. The left panel shows cancer in the mucosa and submucosa layers. The right panel shows cancer in the mucosa, submucosa, and muscle layers.Stage IB squamous cell cancer of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall, and the cancer cells are grade 2-3; OR cancer has formed in the mucosa or submucosa layer and spread into the muscle layer or the connective tissue layer of the esophagus wall, and the cancer cells are grade 1. Grade 1 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 2-3 cancer cells. The tumor is in the lower esophagus or it is not known where the tumor is.

N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
1, XLower, XT2–3, N0, M0T2 = Tumor invades muscularis propria.  
T3 = Tumor invades adventitia.     
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 9.

Table 4. Definitions of TNM Stage IIA Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IIA1, XUpper, middleT2–3, N0, M0T2 = Tumor invades muscularis propria.

Stage IIA squamous cell cancer of the esophagus (1); drawing shows the esophagus and stomach. An inset shows the layers of the esophagus wall with cancer in the mucosa, submucosa, muscle, and connective tissue layers. Also shown are lymph nodes.Stage IIA squamous cell cancer of the esophagus (1). The tumor is in either the upper or middle esophagus. Cancer has spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells are grade 1. Grade 1 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 2-3 cancer cells.

Stage IIA squamous cell cancer of the esophagus (2); drawing shows the esophagus and stomach. An inset shows the layers of the esophagus wall with cancer in the mucosa, submucosa, muscle, and connective tissue layers. Also shown are lymph nodes.Stage IIA squamous cell cancer of the esophagus (2). The tumor is in the lower esophagus or it is not known where the tumor is. Cancer has spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells are grade 2-3. Grade 2-3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 cancer cells.

T3 = Tumor invades adventitia.     
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
2–3Lower, XT2–3, N0, M0T2 = Tumor invades muscularis propria.  
T3 = Tumor invades adventitia.     
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 9.

Table 5. Definitions of TNM Stage IIB Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IIB2–3Upper, middleT2–3, N0, M0T2 = Tumor invades muscularis propria.

Stage IIB squamous cell cancer of the esophagus; drawing shows the esophagus and stomach. A two-panel inset shows the layers of the esophagus wall: the mucosa, submucosa, muscle, and connective tissue layers. The left panel shows cancer in the mucosa, submucosa, muscle, and connective tissue layers. The right panel shows cancer in the mucosa, submucosa, and muscle layers and in 1 lymph node.Stage IIB squamous cell cancer of the esophagus. The tumor is in either the upper or middle esophagus. Cancer has spread into the muscle layer or the connective tissue layer of the esophagus wall, and the cancer cells are grade 2-3; OR cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor. Grade 2-3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 cancer cells.

T3 = Tumor invades adventitia.     
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
AnyAnyT1–2, N1, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.  
T2 = Tumor invades muscularis propria.     
N1 = Metastases in 1–2 regional lymph nodes.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 9.

Table 6. Definitions of TNM Stage IIIA Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IIIAAnyAnyT1–2, N2, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.

Stage IIIA squamous cell cancer of the esophagus (1); drawing shows the  esophagus and stomach. A two-panel inset shows the layers of the esophagus wall: the mucosa, submucosa, muscle, and connective tissue layers. The left panel shows cancer in the mucosa and submucosa layers and in 3 lymph nodes. The right panel shows cancer in the mucosa, submucosa, muscle, and connective tissue layers and in 1 lymph node.Stage IIIA squamous cell cancer of the esophagus (1). Cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 3 to 6 lymph nodes near the tumor; OR cancer has spread into the connective tissue layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor.

Stage IIIA squamous cell cancer of the esophagus (2); drawing shows the esophagus, trachea, and lung. The top inset shows cancer that has spread from the esophagus into the diaphragm and pleura; the aorta, chest wall, and rib are also shown. The bottom inset shows cancer that has spread from the esophagus into the membrane (sac) around the heart.Stage IIIA squamous cell cancer of the esophagus (2). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery.

T2 = Tumor invades muscularis propria.     
N2 = Metastases in 3–6 regional lymph nodes.     
M0 = No distant metastasis.     
AnyAnyT3, N1, M0T3 = Tumor invades adventitia.  
N1 = Metastases in 1–2 regional lymph nodes.     
M0 = No distant metastasis.     
AnyAnyT4a, N0, M0T4a = Resectable tumor invading pleura, pericardium, or diaphragm.  
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 9.

Table 7. Definitions of TNM Stage IIIB Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IIIBAnyAnyT3, N2, M0T3 = Tumor invades adventitia.

Stage IIIB squamous cell cancer of the esophagus; drawing shows the esophagus and stomach. An inset shows the layers of the esophagus wall with cancer in the mucosa, submucosa, muscle, and connective tissue layers. Also shown is cancer in 4 lymph nodes.Stage IIIB squamous cell cancer of the esophagus. Cancer has spread into the connective tissue layer of the esophagus wall. Cancer is found in 3 to 6 lymph nodes near the tumor.

N2 = Metastases in 3–6 regional lymph nodes.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 9.

Table 8. Definitions of TNM Stage IIIC Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IIICAnyAnyT4a, N1–2, M0T4a = Resectable tumor invading pleura, pericardium, or diaphragm.

Stage IIIC squamous cell cancer of the esophagus (1); drawing shows the esophagus, trachea, and lung. The top inset shows cancer that has spread from the esophagus into the diaphragm and pleura; the aorta, chest wall, and rib are also shown. The bottom inset shows cancer that has spread from the esophagus into the membrane (sac) around the heart. Also shown is cancer in  lymph nodes near the esophagus.Stage IIIC squamous cell cancer of the esophagus (1). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery. Cancer is found in 1 to 6 lymph nodes near the tumor.

Stage IIIC squamous cell cancer of the esophagus (2); drawing shows cancer that has spread from the esophagus into the trachea, aorta, and spine. Also shown is cancer in lymph nodes near the esophagus.Stage IIIC squamous cell cancer of the esophagus (2). Cancer has spread into nearby organs, such as the aorta, trachea, or spine, and the cancer cannot be removed by surgery; OR cancer has spread to 7 or more lymph nodes near the tumor.

N1 = Metastases in 1–2 regional lymph nodes.     
N2 = Metastases in 3–6 regional lymph nodes.     
M0 = No distant metastasis.     
AnyAnyT4b, Any N, M0T4b = Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.  
NX = Regional lymph nodes cannot be assessed.     
N0 = No regional lymph node metastasis.     
N1 = Metastases in 1–2 regional lymph nodes.     
N2 = Metastases in 3–6 regional lymph nodes.     
N3 = Metastases in ≥7 regional lymph nodes.     
M0 = No distant metastasis.     
AnyAnyAny T, N3, M0TX = Primary tumor cannot be assessed.  
T0 = No evidence of primary tumor.     
Tis = High-grade dysplasia.d     
T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.     
T1a = Tumor invades lamina propria or muscularis mucosae.     
T1b = Tumor invades submucosa.     
T2 = Tumor invades muscularis propria.     
T3 = Tumor invades adventitia.     
T4 = Tumor invades adjacent structures.     
T4a = Resectable tumor invading pleura, pericardium, or diaphragm.     
T4b = Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.     
N3 = Metastases in ≥7 regional lymph nodes.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–d are at the end of Table 9.

Table 9. Definitions of TNM Stage IV Squamous Cell Carcinoma

Stage Grade Tumor LocationaTNMb,cDescriptionIllustration
IVAnyAnyAny T, Any N, M1TX = Primary tumor cannot be assessed.

Stage IV squamous cell cancer of the esophagus; drawing shows other parts of the body where esophagus cancer may spread, including the lung, liver, adrenal gland, kidney, and bone. An inset shows cancer cells spreading from the esophagus, through the blood and lymph system, to another part of the body where metastatic cancer has formed.Stage IV squamous cell cancer of the esophagus. The cancer has spread to other parts of the body, such as the lung, liver, adrenal gland, kidney, or bone.

T0 = No evidence of primary tumor.     
Tis = High-grade dysplasia.d     
T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.     
T1a = Tumor invades lamina propria or muscularis mucosae.     
T1b = Tumor invades submucosa.     
T2 = Tumor invades muscularis propria.     
T3 = Tumor invades adventitia.     
T4 = Tumor invades adjacent structures.     
T4a = Resectable tumor invading pleura, pericardium, or diaphragm.     
T4b = Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.     
NX = Regional lymph nodes cannot be assessed.     
N0 = No regional lymph node metastasis.     
N1 = Metastases in 1–2 regional lymph nodes.     
N2 = Metastases in 3–6 regional lymph nodes.     
N3 = Metastases in ≥7 regional lymph nodes.     
M1 = Distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
aLocation of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus.
b(1) At least maximal dimension of the tumor must be recorded, and (2) multiple tumors require the T(m) suffix.
cNumber must be recorded for total number of regional nodes sampled and total number of reported nodes with metastasis.
dHigh-grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract.

Staging for adenocarcinoma of the esophagus

Table 10. Definitions of TNM Stage 0 Adenocarcinoma

StageGrade TNMa,bDescription
01, XTis, N0, M0Tis = High-grade dysplasia.c
N0 = No regional lymph node metastasis.   
M0 = No distant metastasis.   
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 18.

Table 11. Definitions of TNM Stage IA Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IA1–2, XT1, N0, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.

Stage IA adenocarcinoma of the esophagus; drawing shows the esophagus and stomach. An inset shows cancer cells in the mucosa and submucosa layers of the esophagus wall. Also shown are the muscle and connective tissue layers of the esophagus wall and lymph nodes.Stage IA adenocarcinoma of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall. The cancer cells are grade 1 or 2. Grade 1 and 2 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 3 cancer cells.

N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–b are at the end of Table 18.

Table 12. Definitions of TNM Stage IB Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IB3T1, N0, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.

Stage IB adenocarcinoma of the esophagus; drawing shows the esophagus and stomach. A two-panel inset shows the layers of the esophagus wall: the mucosa, submucosa, muscle, and connective tissue layers. Also shown are lymph nodes. The left panel shows cancer in the mucosa and submucosa layers. The right panel shows cancer in the mucosa, submucosa, and muscle layers.Stage IB adenocarcinoma of the esophagus. Cancer has formed in the mucosa or submucosa layer of the esophagus wall, and the cancer cells are grade 3. Grade 3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 or 2 cancer cells; OR cancer has formed in the mucosa or submucosa layer and spread into the muscle layer of the esophagus wall, and the cancer cells are grade 1 or 2. Grade 1 and 2 cancer cells look more like normal cells under a microscope and grow and spread more slowly than grade 3 cancer cells.

N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
1–2, XT2, N0, M0T2 = Tumor invades muscularis propria.   
N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–b are at the end of Table 18.

Table 13. Definitions of TNM Stage IIA Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IIA3T2, N0, M0T2 = Tumor invades muscularis propria.

Stage IIA adenocarcinoma of the esophagus; drawing shows the esophagus and stomach. An inset shows cancer in the mucosa, submucosa, and muscle layers of the esophagus wall. Also shown is the connective tissue layer of the esophagus wall and lymph nodes.Stage IIA adenocarcinoma of the esophagus. Cancer has spread into the muscle layer of the esophagus wall. The cancer cells are grade 3. Grade 3 cancer cells look more abnormal under a microscope and grow and spread more quickly than grade 1 or 2 cancer cells.

N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–b are at the end of Table 18.

Table 14. Definitions of TNM Stage IIB Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IIBAnyT3, N0, M0T3 = Tumor invades adventitia.

Stage IIB adenocarcinoma of the esophagus; drawing shows the esophagus and stomach. A two-panel inset shows the layers of the esophagus wall: the mucosa, submucosa, muscle, and connective tissue layers. The left panel shows cancer in the mucosa, submucosa, muscle, and connective tissue layers. The right panel shows cancer in the mucosa, submucosa, and muscle layers and in 1 lymph node.Stage IIB adenocarcinoma of the esophagus. Cancer has spread into the connective tissue layer of the esophagus wall; OR cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor.

N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
AnyT1–2, N1, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.  
T2 = Tumor invades muscularis propria.    
N1 = Metastases in 1–2 regional lymph nodes.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–b are at the end of Table 18.

Table 15. Definitions of TNM Stage IIIA Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IIIAAnyT1–2, N2, M0T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.

Stage IIIA adenocarcinoma of the esophagus (1); drawing shows the esophagus and stomach. A two-panel inset shows the layers of the esophagus wall: the mucosa, submucosa, muscle, and connective tissue layers. The left panel shows cancer in the mucosa and submucosa layers and in 3 lymph nodes. The right panel shows cancer in the mucosa, submucosa, muscle, and connective tissue layers and in 1 lymph node.Stage IIIA adenocarcinoma of the esophagus (1). Cancer is in the mucosa or submucosa layer and may have spread into the muscle layer of the esophagus wall, and cancer is found in 3 to 6 lymph nodes near the tumor; OR cancer has spread into the connective tissue layer of the esophagus wall, and cancer is found in 1 or 2 lymph nodes near the tumor.

Stage IIIA adenocarcinoma of the esophagus (2); drawing shows the esophagus, trachea, and lung. The top inset shows cancer that has spread from the esophagus into the diaphragm and pleura; the aorta, chest wall, and rib are also shown. The bottom inset shows cancer that has spread from the esophagus into the membrane (sac) around the heart.Stage IIIA adenocarcinoma of the esophagus (2). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery.

T2 = Tumor invades muscularis propria.    
N2 = Metastases in 3–6 regional lymph nodes.    
M0 = No distant metastasis.    
AnyT3, N1, M0T3 = Tumor invades adventitia.  
N1 = Metastases in 1–2 regional lymph nodes.    
M0 = No distant metastasis.    
AnyT4a, N0, M0T4a = Resectable tumor invading pleura, pericardium, or diaphragm.  
N0 = No regional lymph node metastasis.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–b are at the end of Table 18.

Table 16. Definitions of TNM Stage IIIB Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IIIBAnyT3, N2, M0T3 = Tumor invades adventitia.

Stage IIIB adenocarcinoma of the esophagus; drawing shows the esophagus and stomach. An inset shows the layers of the esophagus wall with cancer in the mucosa, submucosa, muscle, and connective tissue layers. Also shown is cancer in 4 lymph nodes.Stage IIIB adenocarcinoma of the esophagus. Cancer has spread into the connective tissue layer of the esophagus wall. Cancer is found in 3 to 6 lymph nodes near the tumor.

N2 = Metastases in 3–6 regional lymph nodes.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–b are at the end of Table 18.

Table 17. Definitions of TNM Stage IIIC Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IIICAnyT4a, N1–2, M0T4a = Resectable tumor invading pleura, pericardium, or diaphragm.

Stage IIIC adenocarcinoma of the esophagus (1); drawing shows the esophagus, trachea, and lung. The top inset shows cancer that has spread from the esophagus into the diaphragm and pleura; the aorta, chest wall, and rib are also shown. The bottom inset shows cancer that has spread from the esophagus into the membrane (sac) around the heart. Also shown is cancer in lymph nodes near the esophagus.Stage IIIC adenocarcinoma of the esophagus (1). Cancer has spread into the (a) diaphragm, (b) pleura (tissue that covers the lungs and lines the inner wall of the chest cavity), or (c) membrane (sac) around the heart. The cancer can be removed by surgery. Cancer is found in 1 to 6 lymph nodes near the tumor.

Stage IIIC adenocarcinoma of the esophagus (2); drawing shows cancer that has spread from the esophagus into the trachea, aorta, and spine. Also shown is cancer in lymph nodes near the esophagus.Stage IIIC adenocarcinoma of the esophagus (2). Cancer has spread into nearby organs, such as the aorta, trachea, or spine, and the cancer cannot be removed by surgery; OR cancer has spread to 7 or more lymph nodes near the tumor.

N1 = Metastases in 1–2 regional lymph nodes.    
N2 = Metastases in 3–6 regional lymph nodes.    
M0 = No distant metastasis.    
AnyT4b, Any N, M0T4b = Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.  
NX = Regional lymph nodes cannot be assessed.    
N0 = No regional lymph node metastasis.    
N1 = Metastases in 1–2 regional lymph nodes.    
N2 = Metastases in 3–6 regional lymph nodes.    
N3 = Metastases in ≥7 regional lymph nodes.    
M0 = No distant metastasis.    
AnyAny T, N3, M0TX = Primary tumor cannot be assessed.  
T0 = No evidence of primary tumor.    
Tis = High-grade dysplasia.c    
T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.    
T1a = Tumor invades lamina propria or muscularis mucosae.    
T1b = Tumor invades submucosa.    
T2 = Tumor invades muscularis propria.    
T3 = Tumor invades adventitia.    
T4 = Tumor invades adjacent structures.    
T4a = Resectable tumor invading pleura, pericardium, or diaphragm.    
T4b = Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.    
N3 = N3 = Metastases in ≥7 regional lymph nodes.    
M0 = No distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
The explanations for superscripts a–c are at the end of Table 18.

Table 18. Definitions of TNM Stage IV Adenocarcinoma

StageGrade TNMa,bDescriptionIllustration
IVAnyAny T, Any N, M1TX = Primary tumor cannot be assessed.

Stage IV adenocarcinoma of the esophagus; drawing shows other parts of the body where esophagus cancer may spread, including the lung, liver, adrenal gland, kidney, and bone. An inset shows cancer cells spreading from the esophagus, through the blood and lymph system, to another part of the body where metastatic cancer has formed. Stage IV adenocarcinoma of the esophagus. The cancer has spread to other parts of the body, such as the lung, liver, adrenal gland, kidney, or bone.

T0 = No evidence of primary tumor.    
Tis = High-grade dysplasia.c    
T1 = Tumor invades lamina propria, muscularis mucosae, or submucosa.    
T1a = Tumor invades lamina propria or muscularis mucosae.    
T1b = Tumor invades submucosa.    
T2 = Tumor invades muscularis propria.    
T3 = Tumor invades adventitia.    
T4 = Tumor invades adjacent structures.    
T4a = Resectable tumor invading pleura, pericardium, or diaphragm.    
T4b = Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc.    
NX = Regional lymph nodes cannot be assessed.    
N0 = No regional lymph node metastasis.    
N1 = Metastases in 1–2 regional lymph nodes.    
N2 = Metastases in 3–6 regional lymph nodes.    
N3 = Metastases in ≥7 regional lymph nodes.    
M1 = Distant metastasis.    
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103–15.
a(1) At least maximal dimension of the tumor must be recorded, and (2) multiple tumors require the T(m) suffix.
bNumber must be recorded for total number of regional nodes sampled and total number of reported nodes with metastasis.
cHigh-grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract.

References:

  1. Ziegler K, Sanft C, Zeitz M, et al.: Evaluation of endosonography in TN staging of oesophageal cancer. Gut 32 (1): 16-20, 1991.
  2. Tio TL, Coene PP, den Hartog Jager FC, et al.: Preoperative TNM classification of esophageal carcinoma by endosonography. Hepatogastroenterology 37 (4): 376-81, 1990.
  3. Vazquez-Sequeiros E, Norton ID, Clain JE, et al.: Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma. Gastrointest Endosc 53 (7): 751-7, 2001.
  4. Bonavina L, Incarbone R, Lattuada E, et al.: Preoperative laparoscopy in management of patients with carcinoma of the esophagus and of the esophagogastric junction. J Surg Oncol 65 (3): 171-4, 1997.
  5. Sugarbaker DJ, Jaklitsch MT, Liptay MJ: Thoracoscopic staging and surgical therapy for esophageal cancer. Chest 107 (6 Suppl): 218S-223S, 1995.
  6. Luketich JD, Schauer P, Landreneau R, et al.: Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer. J Thorac Cardiovasc Surg 114 (5): 817-21; discussion 821-3, 1997.
  7. Krasna MJ, Reed CE, Nedzwiecki D, et al.: CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer. Ann Thorac Surg 71 (4): 1073-9, 2001.
  8. Flamen P, Lerut A, Van Cutsem E, et al.: Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma. J Clin Oncol 18 (18): 3202-10, 2000.
  9. Flamen P, Van Cutsem E, Lerut A, et al.: Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer. Ann Oncol 13 (3): 361-8, 2002.
  10. Weber WA, Ott K, Becker K, et al.: Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 19 (12): 3058-65, 2001.
  11. van Westreenen HL, Westerterp M, Bossuyt PM, et al.: Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer. J Clin Oncol 22 (18): 3805-12, 2004.
  12. Meyers BF, Downey RJ, Decker PA, et al.: The utility of positron emission tomography in staging of potentially operable carcinoma of the thoracic esophagus: results of the American College of Surgeons Oncology Group Z0060 trial. J Thorac Cardiovasc Surg 133 (3): 738-45, 2007.
  13. Esophagus and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 103-11.
  14. Korst RJ, Rusch VW, Venkatraman E, et al.: Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg 115 (3): 660-69; discussion 669-70, 1998.

Treatment Option Overview for Esophageal Cancer

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:

Table 19. Standard Treatment Options for Esophageal Cancer

Stage (TNM Staging Criteria)Treatment Options
Stage 0 Esophageal Cancer Surgery
Endoscopic resection 
Stage I Esophageal Cancer Chemoradiation therapy followed by surgery
Surgery alone 
Stage II Esophageal Cancer Chemoradiation followed by surgery
Surgery alone 
Chemotherapy followed by surgery  
Definitive chemoradiation 
Stage III Esophageal Cancer Chemoradiation followed by surgery
Preoperative chemotherapy followed by surgery 
Definitive chemoradiation 
Stage IV Esophageal Cancer Chemoradiation followed by surgery (for patients with stage IVA disease)
Chemotherapy, which has provided partial responses for patients with metastatic distal esophageal adenocarcinomas  
Nd:YAG endoluminal tumor destruction or electrocoagulation 
Endoscopic-placed stents to provide palliation of dysphagia 
Radiation therapy with or without intraluminal intubation and dilation 
Intraluminal brachytherapy to provide palliation of dysphagia 
Recurrent Esophageal Cancer Palliative use of any of the standard therapies, including supportive care

Surgery

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. [6]

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. [7] 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 [8] 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. [12] Similarly, no differences in long-term quality of life (QOL) using validated QOL instruments have been reported. [13] 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. [14]

In the United States, the median age of patients who present with esophageal cancer is 67 years. [15] 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. [16][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%. [7] 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. [21]

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) [23], 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):

  1. The CROSS study randomly assigned 366 patients with resectable esophageal or junctional cancers to receive either surgery alone or weekly administration of carboplatin (dose titrated to achieve an AUC [area under the curve] of 2 mg/mL/minute) and paclitaxel (50 mg/m2 of BSA [body surface area]) and concurrent radiation therapy (41.4 Gy in 23 fractions) administered over 5 weeks. Most patients enrolled in the CROSS trial (75%) had adenocarcinoma. [21] [24][Level of evidence: 1iiA]
  2. A multicenter prospective randomized trial compared preoperative combined chemotherapy (i.e., cisplatin) and radiation therapy (37 Gy in 3.7 Gy fractions) versus surgery alone in patients with squamous cell carcinoma. [17][Level of evidence: 1iiA]
  3. In patients with adenocarcinoma of the esophagus, a single-institution phase III trial was conducted in patients treated with induction chemoradiation therapy consisting of 5-fluorouracil (5-FU), cisplatin, and 40 Gy (2.67 Gy fractions) plus surgery compared with resection alone. [18][Level of evidence: 1iiA]
  4. A subsequent single-institution trial randomly assigned patients (75% with adenocarcinoma) to 5-FU, cisplatin, vinblastine, and radiation therapy (1.5 Gy twice daily to a total of 45 Gy) plus resection versus esophagectomy alone. [19][Level of evidence: 1iiA]
  5. An intergroup trial (CALGB-9781) planned to randomly assign 475 patients with resectable squamous cell or adenocarcinoma of the thoracic esophagus to treatment with preoperative chemoradiation therapy (5-FU, cisplatin, and 50.4 Gy) followed by esophagectomy and nodal dissection or surgery alone. The trial was closed as a result of poor patient accrual; however, results from the 56 enrolled patients, with a median follow-up of 6 years, were reported. [20][Level of evidence: 1iiA]
  6. To further evaluate the impact of neoadjuvant chemoradiation therapy for early-stage disease, FFCD 9901 randomly assigned 195 patients with stage I or stage II esophageal cancer to receive surgery alone or neoadjuvant chemoradiation therapy (45 Gy in 25 fractions administered with two courses of 5-FU [800 mg/m2] and cisplatin [75 mg/m2]) followed by surgery. [23][Level of evidence: 1iiA]

Preoperative Chemotherapy

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. [28] Compared with preoperative chemotherapy alone, preoperative chemoradiation therapy improves pathologic response and may improve outcomes. [29]

Evidence (preoperative chemotherapy):

  1. An intergroup trial (NCT00525785) randomly assigned 440 patients with local and operable esophageal cancer of any cell type to three cycles of preoperative 5-FU and cisplatin followed by surgery and two additional cycles of chemotherapy versus surgery alone. [28][Level of evidence: 1iiA]
  2. The Medical Research Council Oesophageal Cancer Working Party randomly assigned 802 patients with resectable esophageal cancer, also of any cell type, to two cycles of preoperative 5-FU and cisplatin followed by surgery versus surgery alone. [25][Level of evidence: 1iiA]

    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.

  3. The Japanese Clinical Oncology Group randomly assigned 330 patients with clinical stage II or III, excluding T4, squamous cell carcinomas to receive either two cycles of preoperative cisplatin and 5-FU followed by surgery or surgery followed by postoperative chemotherapy of the same regimen. A planned interim analysis was conducted after patient accrual; although the primary endpoint of PFS was not met, there was a significant benefit in OS among patients treated with preoperative chemotherapy (P = .01). As a result of these findings, the Data and Safety Monitoring Committee recommended early closure of the study. [26][Level of evidence: 1iiC]
  4. The Fédération Nationale des Centres de Lutte contre le Cancer (FNCLCC) and the Fédération Francophone de Cancérologie Digestive (FFCD) randomly assigned 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction, or stomach to receive either perioperative chemotherapy and surgery (n = 113) or surgery alone (n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous (IV) cisplatin (100 mg/m2) on day 1 and continuous IV infusion of 5-FU (800 mg/m2) for 5 consecutive days (day 1–5) every 28 days, and three or four postoperative cycles of the same regimen. [27][Level of evidence: 1iiA]
  5. The Preoperative Chemotherapy or Radiochemotherapy in Esophago-gastric Adenocarcinoma Trial (POET) sought to evaluate the additional benefit of radiation therapy to preoperative chemotherapy. Patients were randomly assigned to receive either induction chemotherapy (15 weeks) followed by surgery or chemotherapy (12 weeks) followed by chemoradiation therapy (3 weeks) followed by surgery. [29][Level of evidence: 1iiA]

Definitive Chemoradiation

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):

  1. A Radiation Therapy Oncology Group trial (RTOG-8501) randomly assigned patients to chemotherapy and radiation therapy versus radiation therapy alone. Patients were randomly assigned to receive radiation therapy alone (64 Gy in 32 fractions) or chemoradiation (50 Gy in 25 fractions) with concurrent cisplatin (75 mg/m2) and continuous-infusion 5-FU (1,000 mg/m2 on days 1 to 4 in weeks 1 and 5 followed by two additional cycles of chemotherapy administered 3 weeks apart). [30][Level of evidence: 1iiA]
  2. Intergroup-0123 (RTOG-9405 ) was conducted in an attempt to improve upon the results of RTOG-8501. Intergroup-0123 randomly assigned 236 patients with localized esophageal tumors to undergo chemoradiation with high-dose radiation therapy (64.8 Gy) and four monthly cycles of 5-FU and cisplatin versus conventional-dose radiation therapy (50.4 Gy) and the same chemotherapy schedule. [31][Level of evidence: 1iiA]
  3. An Eastern Cooperative Oncology Group trial (EST-1282) evaluated 135 patients. [34][Level of evidence: 1iiA]
  4. The PRODIGE5/ACCORD17 (NCT00861094) trial sought to evaluate and compare the efficacy and safety of FOLFOX (oxaliplatin, fluorouracil, and leucovorin calcium) versus 5-FU and cisplatin as the chemotherapy backbone among patients treated with definitive chemoradiation for localized esophageal cancer. In this multicenter randomized phase II and III trial, 267 patients were randomly assigned to receive either six cycles of FOLFOX (three cycles concomitant with radiation therapy), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), bolus 5-FU (400 mg/m2) and infusion 5-FU (1,600 mg/m2 over 46 hours) or four cycles of 5-FU (1,000 mg/m2 for 4 days) and cisplatin (75 mg/m2 on day 1). All patients received radiation therapy (50 Gy in 25 fractions). [35][Level of evidence: 1iiDiii]
  5. A phase III German trial also compared induction chemotherapy (three courses of bolus 5-FU, leucovorin, etoposide, and cisplatin) followed by chemoradiation therapy (cisplatin, etoposide, and 40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiation therapy (at least 65 Gy) without surgery (arm B) for patients with T3 or T4 squamous cell carcinoma of the esophagus. OS was the primary outcome. [32][Level of evidence: 1iiA]
  6. FFCD 9102 (NCT00416858) randomly assigned 259 patients with T3N0–1M0 thoracic esophageal cancer to receive either two cycles of 5-FU and cisplatin (days 1–5 and 22–26) and either conventional radiation (46 Gy in 4.5 weeks) or split course (15 Gy, days 1–5 and 22–26). Patients with response were then randomly assigned to receive either surgical resection (arm A) or continuation of chemoradiation (arm B: three cycles of 5FU plus cisplatin and either conventional 20 Gy or split-course 15 Gy radiation therapy). [33][Level of evidence: 1iiA]

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.

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  13. de Boer AG, van Lanschot JJ, van Sandick JW, et al.: Quality of life after transhiatal compared with extended transthoracic resection for adenocarcinoma of the esophagus. J Clin Oncol 22 (20): 4202-8, 2004.
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  27. Ychou M, Boige V, Pignon JP, et al.: Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29 (13): 1715-21, 2011.
  28. Kelsen DP, Ginsberg R, Pajak TF, et al.: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 339 (27): 1979-84, 1998.
  29. Stahl M, Walz MK, Stuschke M, et al.: Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27 (6): 851-6, 2009.
  30. Cooper JS, Guo MD, Herskovic A, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 281 (17): 1623-7, 1999.
  31. Minsky BD, Pajak TF, Ginsberg RJ, et al.: INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 20 (5): 1167-74, 2002.
  32. Stahl M, Stuschke M, Lehmann N, et al.: Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23 (10): 2310-7, 2005.
  33. Bedenne L, Michel P, Bouché O, et al.: Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25 (10): 1160-8, 2007.
  34. Smith TJ, Ryan LM, Douglass HO Jr, et al.: Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys 42 (2): 269-76, 1998.
  35. Conroy T, Galais MP, Raoul JL, et al.: Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol 15 (3): 305-14, 2014.
  36. Ténière P, Hay JM, Fingerhut A, et al.: Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet 173 (2): 123-30, 1991.
  37. Fok M, Sham JS, Choy D, et al.: Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery 113 (2): 138-47, 1993.

Stage 0 Esophageal Cancer

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]

  1. Surgery.
  2. Endoscopic resection.

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.

References:

  1. Rusch VW, Levine DS, Haggitt R, et al.: The management of high grade dysplasia and early cancer in Barrett's esophagus. A multidisciplinary problem. Cancer 74 (4): 1225-9, 1994.
  2. Heitmiller RF, Redmond M, Hamilton SR: Barrett's esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy. Ann Surg 224 (1): 66-71, 1996.
  3. Pech O, Bollschweiler E, Manner H, et al.: Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett's esophagus at two high-volume centers. Ann Surg 254 (1): 67-72, 2011.
  4. Prasad GA, Wu TT, Wigle DA, et al.: Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett's esophagus. Gastroenterology 137 (3): 815-23, 2009.

Stage I Esophageal Cancer

Standard Treatment Options for Stage I Esophageal Cancer

Standard treatment options for stage I esophageal cancer include the following: [1] [2] [3] [4] [5]

  1. Chemoradiation followed by surgery.
  2. Surgery alone.

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI website.

References:

  1. Bosset JF, Gignoux M, Triboulet JP, et al.: Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 337 (3): 161-7, 1997.
  2. Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335 (7): 462-7, 1996.
  3. Urba SG, Orringer MB, Turrisi A, et al.: Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 19 (2): 305-13, 2001.
  4. Tepper J, Krasna MJ, Niedzwiecki D, et al.: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26 (7): 1086-92, 2008.
  5. van Hagen P, Hulshof MC, van Lanschot JJ, et al.: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366 (22): 2074-84, 2012.

Stage II Esophageal Cancer

Standard Treatment Options for Stage II Esophageal Cancer

Standard treatment options for stage II esophageal cancer include the following: [1]

  1. Chemoradiation followed by surgery. [1] [2] [3]
  2. Surgery alone. [4] [5] [6] [7]
  3. Chemotherapy followed by surgery. [8] [9] [10]
  4. Definitive chemoradiation. [11] [12]

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI website.

References:

  1. Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335 (7): 462-7, 1996.
  2. Tepper J, Krasna MJ, Niedzwiecki D, et al.: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26 (7): 1086-92, 2008.
  3. van Hagen P, Hulshof MC, van Lanschot JJ, et al.: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366 (22): 2074-84, 2012.
  4. Urba SG, Orringer MB, Turrisi A, et al.: Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 19 (2): 305-13, 2001.
  5. Bosset JF, Gignoux M, Triboulet JP, et al.: Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 337 (3): 161-7, 1997.
  6. Conroy T, Galais MP, Raoul JL, et al.: Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol 15 (3): 305-14, 2014.
  7. Mariette C, Dahan L, Mornex F, et al.: Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol 32 (23): 2416-22, 2014.
  8. Medical Research Council Oesophageal Cancer Working Group: Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359 (9319): 1727-33, 2002.
  9. Ando N, Kato H, Igaki H, et al.: A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19 (1): 68-74, 2012.
  10. Ychou M, Boige V, Pignon JP, et al.: Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29 (13): 1715-21, 2011.
  11. Stahl M, Stuschke M, Lehmann N, et al.: Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23 (10): 2310-7, 2005.
  12. Bedenne L, Michel P, Bouché O, et al.: Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25 (10): 1160-8, 2007.

Stage III Esophageal Cancer

Standard Treatment Options for Stage III Esophageal Cancer

Standard treatment options for stage III esophageal cancer include the following:

  1. Chemoradiation followed by surgery. [1] [2] [3]
  2. Preoperative chemotherapy followed by surgery. [4] [5] [6]
  3. Definitive chemoradiation. [7] [8] [9]

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI website.

References:

  1. Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335 (7): 462-7, 1996.
  2. Tepper J, Krasna MJ, Niedzwiecki D, et al.: Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26 (7): 1086-92, 2008.
  3. van Hagen P, Hulshof MC, van Lanschot JJ, et al.: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366 (22): 2074-84, 2012.
  4. Medical Research Council Oesophageal Cancer Working Group: Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359 (9319): 1727-33, 2002.
  5. Ando N, Kato H, Igaki H, et al.: A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19 (1): 68-74, 2012.
  6. Ychou M, Boige V, Pignon JP, et al.: Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29 (13): 1715-21, 2011.
  7. Conroy T, Galais MP, Raoul JL, et al.: Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol 15 (3): 305-14, 2014.
  8. Stahl M, Stuschke M, Lehmann N, et al.: Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23 (10): 2310-7, 2005.
  9. Bedenne L, Michel P, Bouché O, et al.: Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25 (10): 1160-8, 2007.

Stage IV Esophageal Cancer

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. [1]

Treatment options for stage IV esophageal cancer include the following:

  1. Chemoradiation followed by surgery (for patients with stage IVA disease).
  2. Chemotherapy, which has provided partial responses for patients with metastatic distal esophageal adenocarcinomas. [2] [3] [4]
  3. Nd:YAG endoluminal tumor destruction or electrocoagulation. [5]
  4. Endoscopic-placed stents to provide palliation of dysphagia. [6]
  5. Radiation therapy with or without intraluminal intubation and dilation.
  6. Intraluminal brachytherapy to provide palliation of dysphagia. [7] [8]

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. [10][Level of evidence: 1iiA]

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI website.

References:

  1. Enzinger PC, Ilson DH, Kelsen DP: Chemotherapy in esophageal cancer. Semin Oncol 26 (5 Suppl 15): 12-20, 1999.
  2. Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.
  3. Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.
  4. Taïeb J, Artru P, Baujat B, et al.: Optimisation of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of hydroxyurea, leucovorin, 5-FU and cisplatin (HLFP regimen) for metastatic oesophageal cancer. Eur J Cancer 38 (5): 661-6, 2002.
  5. Bourke MJ, Hope RL, Chu G, et al.: Laser palliation of inoperable malignant dysphagia: initial and at death. Gastrointest Endosc 43 (1): 29-32, 1996.
  6. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.
  7. Sur RK, Levin CV, Donde B, et al.: Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study. Int J Radiat Oncol Biol Phys 53 (1): 127-33, 2002.
  8. Gaspar LE, Nag S, Herskovic A, et al.: American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA. Int J Radiat Oncol Biol Phys 38 (1): 127-32, 1997.
  9. Conroy T, Etienne PL, Adenis A, et al.: Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival. Ann Oncol 13 (5): 721-9, 2002.
  10. Bang YJ, Van Cutsem E, Feyereislova A, et al.: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376 (9742): 687-97, 2010.

Recurrent Esophageal Cancer

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:

Current Clinical Trials

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.

General information about clinical trials is also available from the NCI website.

Changes to This Summary (02/04/2016)

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.

About This PDQ Summary

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 reviewer for Esophageal Cancer Treatment is:

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:

PDQ® Adult Treatment Editorial Board. PDQ Esophageal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/esophageal/hp/esophageal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389338]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

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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Date last modified: 2016-02-04

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