医療専門家向け Esophageal Cancer Treatment (Adult) (PDQ®)

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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult 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.

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).

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General Information About Esophageal Cancer

Two histologic types account for the majority of malignant esophageal neoplasms: adenocarcinoma and squamous cell 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 2020:[ 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 ] Most adenocarcinomas are located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown.

Anatomy

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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 near 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:

参考文献

1. American Cancer Society: Cancer Facts and Figures 2020. Atlanta, Ga: American Cancer Society, 2020. Available online. Last accessed May 12, 2020.[PUBMED Abstract]
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.[PUBMED Abstract]
3. Blot WJ, McLaughlin JK: The changing epidemiology of esophageal cancer. Semin Oncol 26 (5 Suppl 15): 2-8, 1999.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
6. Ginsberg RJ: Cancer treatment in the elderly. J Am Coll Surg 187 (4): 427-8, 1998.[PUBMED Abstract]
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.[PUBMED Abstract]
8. Reed MF, Tolis G, Edil BH, et al.: Surgical treatment of esophageal high-grade dysplasia. Ann Thorac Surg 79 (4): 1110-5; discussion 1110-5, 2005.[PUBMED Abstract]

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 (Adult) 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 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 fluorine F 18-fludeoxyglucose (18F-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 18F-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 AJCC has designated staging by TNM (tumor, node, metastasis) 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 for Gastric Cancer section in the PDQ summary on Gastric Cancer Treatment for more information.)

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 is attempted when possible.

Table 1. Definitions of Primary Tumor, Regional Lymph Node, Distant Metastasis, Histologic Grade for Squamous Cell Carcinoma and Adenocarcinoma, and Location for Squamous Cell Carcinoma of the Esophagus^a

T Category/Criteria	N Category/Criteria	M Category/Criteria	G Definition	L Category/Criteria
T = definition of primary tumor; N = definition of regional lymph nodes; M = definition of distant metastasis; G = definition of histologic grade; L = definition of location.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
bLocation is defined by the position of the epicenter of the tumor in the esophagus.
TX = Tumor cannot be assessed.	NX = Regional lymph nodes cannot be assessed.	M0 = No distant metastasis.	GX = Grade cannot be assessed.
T0 = No evidence of primary tumor.	N0 = No regional lymph node metastasis.	M1 = Distant metastasis.	G1 = Well differentiated.
Tis = High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane.	N1 = Metastasis in one or two regional lymph nodes.		G2 = Moderately differentiated.
			G3 = Poorly differentiated, undifferentiated.
T1 = Tumor invades the lamina propria, muscularis mucosae, or submucosa.	N2 = Metastasis in three to six regional lymph nodes.
	N3 = Metastasis in seven or more regional lymph nodes.
T1a = Tumor invades the lamina propria or muscularis mucosae.
T1b = Tumor invades the submucosa.
T2 = Tumor invades the muscularis propria.
T3 = Tumor invades adventitia.
T4 = Tumor invades adjacent structures.
T4a = Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum.
T4b = Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway.

Staging for squamous cell carcinoma of the esophagus

Table 2. Definitions of pTNM Stage 0 for Squamous Cell Carcinoma of the Esophagus^a

Stage	TNM	Grade	Tumor Location	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; L = tumor location; N/A = not applicable; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202
0	Tis, N0, M0	N/A	Any	Tis = High grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane.	画像を拡大する
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G1 = N/A.
				Any L = See Table 1.

Table 3. Definitions of pTNM Stages IA and IB for Squamous Cell Carcinoma of the Esophagus^a

Stage	TNM	Grade	Tumor Location	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; L = tumor location; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
IA	Tia, N0, M0	G1	Any	–T1a = Tumor invades the lamina propria or muscularis mucosae.	画像を拡大する
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G1 = Well differentiated.
				Any L = See Table 1.
	T1a, N0, M0	GX	Any	–T1a = Tumor invades the lamina propria or muscularis mucosae.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				GX = Grade cannot be assessed.
				Any L = See Table 1.
IB	T1a, N0, M0	G2–G3	Any	–T1a = Tumor invades the lamina propria or muscularis mucosae.	画像を拡大する
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G2 = Moderately differentiated.
				G3 = Poorly differentiated, undifferentiated.
				Any L = See Table 1.
	T1b, N0, M0	G1–G3	Any	–T1b = Tumor invades the submucosa.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G1 = Well differentiated.
				G2 = Moderately differentiated.
				G3 = Poorly differentiated, undifferentiated.
				Any L = See Table 1.
	T1b, N0, M0	GX	Any	–T1b = Tumor invades the submucosa.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				GX = Grade cannot be assessed.
				Any L = See Table 1.
	T2, N0, M0	G1	Any	T2 = Tumor invades the muscularis propria.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G1 = Well differentiated.
				Any L = See Table 1.

Table 4. Definitions of pTNM Stages IIA and IIB for Squamous Cell Carcinoma of the Esophagus^a

Stage	TNM	Grade	Tumor Location	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; L = tumor location; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
bLocation is defined by the position of the epicenter of the tumor in the esophagus.
IIA	T2, N0, M0	GX	Any	T2 = Tumor invades the muscularis propria.	画像を拡大する 画像を拡大する 画像を拡大する
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				GX = Grade cannot be assessed.
				Any L = See Table 1.
	T2, N0, M0	G2–G3	Any	T2 = Tumor invades the muscularis propria.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G2 = Moderately differentiated.
				G3 = Poorly differentiated, undifferentiated.
				Any L = See Table 1.
	T3, N0, M0	Any	Lower	T3 = Tumor invades adventitia.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Lower = Lower border of inferior pulmonary vein to stomach, including gastroesophageal junction.
	T3, N0, M0	G1	Upper/middle	T3 = Tumor invades adventitia.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G1 = Well differentiated.
				Upper = Cervical esophagus to lower border of azygos vein.
				Middle = Lower border of azygos vein to lower border of inferior pulmonary vein.
IIB	T3, N0, M0	G2–G3	Upper/middle	T3 = Tumor invades adventitia.	画像を拡大する 画像を拡大する 画像を拡大する
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				G2 = Moderately differentiated.
				G3 = Poorly differentiated, undifferentiated.
				Upper = Cervical esophagus to lower border of azygos vein.
				Middle = Lower border of azygos vein to lower border of inferior pulmonary vein.
	T3, N0, M0	GX	Any	T3 = Tumor invades adventitia.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				GX = Grade cannot be assessed.
				Any L = See Table 1.
	T3, N0, M0	Any	Location X	T3 = Tumor invades adventitia.
				N0 = No regional lymph node metastasis.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Location X = Location unknown.
	T1, N1, M0	Any	Any	T1 = Tumor invades the lamina propria, muscularis mucosae, or submucosa.
				N1 = Metastasis in one or two regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.

Table 5. Definitions of pTNM Stages IIIA and IIIB for Squamous Cell Carcinoma of the Esophagus^a

Stage	TNM	Grade	Tumor Location	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; L = tumor location; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
bLocation is defined by the position of the epicenter of the tumor in the esophagus.
IIIA	T1, N2, M0	Any	Any	T1 = Tumor invades the lamina propria, muscularis mucosae, or submucosa.	画像を拡大する
				–T1a = Tumor invades the lamina propria or muscularis mucosae.
				–T1b = Tumor invades the submucosa.
				N2 = Metastasis in three to six regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
	T2, N1, M0	Any	Any	T2 = Tumor invades the muscularis propria.
				N1 = Metastasis in one or two regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
IIIB	T2, N2, M0	Any	Any	T2 = Tumor invades the muscularis propria.	画像を拡大する
				N2 = Metastasis in three to six regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
	T3, N1–N2, M0	Any	Any	T3 = Tumor invades adventitia.
				N1 = Metastasis in one or two regional lymph nodes.
				N2 = Metastasis in three to six regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
	T4a, N0–1, M0	Any	Any	–T4a = Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum.	画像を拡大する
				N0 = No regional lymph node metastasis.
				N1 = Metastasis in one or two regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.

Table 6. Definitions of pTNM Stages IVA and IVB for Squamous Cell Carcinoma of the Esophagus^a

Stage	TNM	Grade	Tumor Location	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; L = tumor location; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
bLocation is defined by the position of the epicenter of the tumor in the esophagus.
IVA	T4a, N2, M0	Any	Any	–T4a = Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum.	画像を拡大する
				N2 = Metastasis in three to six regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
	T4b, N0–2, M0	Any	Any	–T4b = Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway.	画像を拡大する
				N0 = No regional lymph node metastasis.
				N1 = Metastasis in one or two regional lymph nodes.
				N2 = Metastasis in three to six regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
	Any T, N3, M0	Any	Any	Any T = See Table 1.	画像を拡大する
				N3 = Metastasis in seven or more regional lymph nodes.
				M0 = No distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.
IVB	Any T, Any N, M1	Any	Any	Any T = See Table 1.	画像を拡大する
				Any N = See Table 1.
				M1 = Distant metastasis.
				Any G = See Table 1.
				Any L = See Table 1.

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Staging for adenocarcinoma of the esophagus

Table 7. Definitions of pTNM Stage 0 for Adenocarcinoma of the Esophagus^a

Stage	TNM	Grade	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; N/A = not applicable; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
0	Tis, N0, M0	N/A	Tis = High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane.	画像を拡大する
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.

Table 8. Definitions of pTNM Stages IA, IB, and IC for Adenocarcinoma of the Esophagus^a

Stage	TNM	Grade	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
IA	T1a, N0, M0	G1	–T1a = Tumor invades the lamina propria or muscularis mucosae.	画像を拡大する
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			G1 = Well differentiated.
	T1a, N0, M0	GX	–T1a = Tumor invades the lamina propria or muscularis mucosae.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			GX = Grade cannot be assessed.
IB	T1a, N0, M0	G2	–T1a = Tumor invades the lamina propria or muscularis mucosae.	画像を拡大する
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			G2 = Moderately differentiated.
	T1b, N0, M0	G1–2	–T1b = Tumor invades the submucosa.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			G1 = Well differentiated.
			G2 = Moderately differentiated.
	T1b, N0, M0	GX	–T1b = Tumor invades the submucosa.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			GX = Grade cannot be assessed.
IC	T1, N0, M0	G3	T1 = Tumor invades the lamina propria, muscularis mucosae, or submucosa.	画像を拡大する
			–T1a = Tumor invades the lamina propria or muscularis mucosae.
			–T1b = Tumor invades the submucosa.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			G3 = Poorly differentiated, undifferentiated.
	T2, N0, M0	G1–2	T2 = Tumor invades the muscularis propria.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			G1 = Well differentiated.
			G2 = Moderately differentiated.

Table 9. Definitions of pTNM Stages IIA and IIB for Adenocarcinoma of the Esophagus^a

Stage	TNM	Grade	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
IIA	T2, N0, M0	G3	T2 = Tumor invades the muscularis propria.	画像を拡大する
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			G3 = Poorly differentiated, undifferentiated.
	T2, N0, M0	GX	T2 = Tumor invades the muscularis propria.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			GX = Grade cannot be assessed.
IIB	T1, N1, M0	Any	T1 = Tumor invades the lamina propria, muscularis mucosae, or submucosa.	画像を拡大する
			–T1a = Tumor invades the lamina propria or muscularis mucosae.
			–T1b = Tumor invades the submucosa.
			N1 = Metastasis in one or two regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
	T3, N0, M0	Any	T3 = Tumor invades adventitia.
			N0 = No regional lymph node metastasis.
			M0 = No distant metastasis.
			Any G = See Table 1.

Table 10. Definitions of pTNM Stages IIIA and IIIB for Adenocarcinoma of the Esophagus^a

Stage	TNM	Grade	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
IIIA	T1, N2, M0	Any	T1 = Tumor invades the lamina propria, muscularis mucosae, or submucosa.	画像を拡大する
			–T1a = Tumor invades the lamina propria or muscularis mucosae.
			–T1b = Tumor invades the submucosa.
			N2 = Metastasis in three to six regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
	T2, N1, M0	Any	T2 = Tumor invades the muscularis propria.
			N1 = Metastasis in one or two regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
IIIB	T2, N2, M0	Any	T2 = Tumor invades the muscularis propria.	画像を拡大する
			N2 = Metastasis in three to six regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
	T3, N1–2, M0	Any	T3 = Tumor invades adventitia.
			N1 = Metastasis in one or two regional lymph nodes.
			N2 = Metastasis in three to six regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
	T4a, N0–1, M0	Any	–T4a = Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum.	画像を拡大する
			N0 = No regional lymph node metastasis.
			N1 = Metastasis in one or two regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.

Table 11. Definitions of pTNM Stages IVA and IVB for Adenocarcinoma of the Esophagus^a

Stage	TNM	Grade	Description	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; G = grade; p = pathological.
aReprinted with permission from AJCC: Esophageal and esophagogastric junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 185–202.
IVA	T4a, N2, M0	Any	–T4a = Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum.	画像を拡大する
			N2 = Metastasis in three to six regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
	T4b, N0–2, M0	Any	–T4b = Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway.	画像を拡大する
			N0 = No regional lymph node metastasis.
			N1 = Metastasis in one or two regional lymph nodes.
			N2 = Metastasis in three to six regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
	Any T, N3, M0	Any	Any T = See Table 1.	画像を拡大する
			N3 = Metastasis in seven or more regional lymph nodes.
			M0 = No distant metastasis.
			Any G = See Table 1.
IVB	Any T, Any N, M1	Any	Any T = See Table 1.	画像を拡大する
			Any N = See Table 1.
			M1 = Distant metastasis.
			Any G = See Table 1.

参考文献

1. Ziegler K, Sanft C, Zeitz M, et al.: Evaluation of endosonography in TN staging of oesophageal cancer. Gut 32 (1): 16-20, 1991.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
5. Sugarbaker DJ, Jaklitsch MT, Liptay MJ: Thoracoscopic staging and surgical therapy for esophageal cancer. Chest 107 (6 Suppl): 218S-223S, 1995.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
13. Rice TW, Kelsen D, Blackstone EH, et al.: Esophagus and Esophagogastric Junction. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 185-202.[PUBMED Abstract]
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.[PUBMED Abstract]

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 12. Standard Treatment Options for Esophageal Cancer

Stage (	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 (in 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 [NCT00003118]) 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 and the 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 [NCT00002631]) 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 oxaliplatin, fluorouracil, and leucovorin calcium (FOLFOX) 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 therapy (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 5-FU 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.

参考文献

1. Tietjen TG, Pasricha PJ, Kalloo AN: Management of malignant esophageal stricture with esophageal dilation and esophageal stents. Gastrointest Endosc Clin N Am 4 (4): 851-62, 1994.[PUBMED Abstract]
2. Lightdale CJ, Heier SK, Marcon NE, et al.: Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial. Gastrointest Endosc 42 (6): 507-12, 1995.[PUBMED Abstract]
3. Kubba AK: Role of photodynamic therapy in the management of gastrointestinal cancer. Digestion 60 (1): 1-10, 1999 Jan-Feb.[PUBMED Abstract]
4. Heier SK, Heier LM: Tissue sensitizers. Gastrointest Endosc Clin N Am 4 (2): 327-52, 1994.[PUBMED Abstract]
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.[PUBMED Abstract]
6. Lerut T, Coosemans W, Van Raemdonck D, et al.: Surgical treatment of Barrett's carcinoma. Correlations between morphologic findings and prognosis. J Thorac Cardiovasc Surg 107 (4): 1059-65; discussion 1065-6, 1994.[PUBMED Abstract]
7. Kelsen DP, Bains M, Burt M: Neoadjuvant chemotherapy and surgery of cancer of the esophagus. Semin Surg Oncol 6 (5): 268-73, 1990.[PUBMED Abstract]
8. Saxon RR, Morrison KE, Lakin PC, et al.: Malignant esophageal obstruction and esophagorespiratory fistula: palliation with a polyethylene-covered Z-stent. Radiology 202 (2): 349-54, 1997.[PUBMED Abstract]
9. Campbell WR, Taylor SA, Pierce GE, et al.: Therapeutic alternatives in patients with esophageal cancer. Am J Surg 150 (6): 665-8, 1985.[PUBMED Abstract]
10. Mellow MH, Pinkas H: Endoscopic therapy for esophageal carcinoma with Nd:YAG laser: prospective evaluation of efficacy, complications, and survival. Gastrointest Endosc 30 (6): 334-9, 1984.[PUBMED Abstract]
11. Karlin DA, Fisher RS, Krevsky B: Prolonged survival and effective palliation in patients with squamous cell carcinoma of the esophagus following endoscopic laser therapy. Cancer 59 (11): 1969-72, 1987.[PUBMED Abstract]
12. Hulscher JB, van Sandick JW, de Boer AG, et al.: Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 347 (21): 1662-9, 2002.[PUBMED Abstract]
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.[PUBMED Abstract]
14. Santillan AA, Farma JM, Meredith KL, et al.: Minimally invasive surgery for esophageal cancer. J Natl Compr Canc Netw 6 (9): 879-84, 2008.[PUBMED Abstract]
15. Ginsberg RJ: Cancer treatment in the elderly. J Am Coll Surg 187 (4): 427-8, 1998.[PUBMED Abstract]
16. Ellis FH, Williamson WA, Heatley GJ: Cancer of the esophagus and cardia: does age influence treatment selection and surgical outcomes? J Am Coll Surg 187 (4): 345-51, 1998.[PUBMED Abstract]
17. 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.[PUBMED Abstract]
18. 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.[PUBMED Abstract]
19. 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.[PUBMED Abstract]
20. 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.[PUBMED Abstract]
21. 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.[PUBMED Abstract]
22. Oppedijk V, van der Gaast A, van Lanschot JJ, et al.: Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol 32 (5): 385-91, 2014.[PUBMED Abstract]
23. 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.[PUBMED Abstract]
24. Shapiro J, van Lanschot JJ, Hulshof MC, et al.: Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16 (9): 1090-8, 2015.[PUBMED Abstract]
25. 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.[PUBMED Abstract]
26. 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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
34. Smith TJ, Ryan LM, Douglass HO, 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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

Stage 0 Esophageal Cancer Treatment

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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献

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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

Stage I Esophageal Cancer Treatment

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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献

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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

Stage II Esophageal Cancer Treatment

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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献

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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

Stage III Esophageal Cancer Treatment

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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献

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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

Stage IV Esophageal Cancer Treatment

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-fluorouracil, 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

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

参考文献

1. Enzinger PC, Ilson DH, Kelsen DP: Chemotherapy in esophageal cancer. Semin Oncol 26 (5 Suppl 15): 12-20, 1999.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]
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.[PUBMED Abstract]

Recurrent Esophageal Cancer Treatment

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 for Esophageal Cancer section of this summary.

Standard treatment options:

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Changes to This Summary (05/07/2020)

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.

Editorial changes were made to this summary.

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 adult 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.

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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.

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The preferred citation for this PDQ summary is:

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

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