TNM Classification for Esophageal Cancer

The American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification system for esophageal and esophagogastric junction cancer is provided below, along with histologic grade and anatomic/prognostic groups for squamous cell carcinoma and adenocarcinoma.^{[1, 2]}

T/N staging

The T indicator is related to the extent of tumor invasion. The T stage (Table 1) has a direct impact on the patient’s stage, the likelihood of metastatic nodal disease, and outcome.^[3]The location of the primary tumor does not have a direct correlation with prognosis, but influences management decisions, especially for non-metastatic disease, including surgical planning, consideration of neoadjuvant therapy, and determining radiation fields.

Positron emission tomography–computed tomography (PET-CT) has limited use in the T staging of esophageal cancers; however, it can demonstrate signs of adjacent organ infiltration. Endoscopic ultrasonography (EUS) is the imaging modality of choice for the evaluation of T staging.^[4]Advanced (T4) disease is more accurately identified than early (T1) disease^[5]; differentiating Tis, T1a, and T1b disease can be challenging.^[6]

EUS can also be used to evaluate regional lymph nodes, allowing for N staging, especially with use of fine needle aspiration (FNA). CT and PET are inadequate for staging celiac and mediastinal lymph nodes.^{[7, 8, 9, 10]}However, CT and EUS together can increase the accuracy of regional lymph node evaluation.^{[7, 11]}

For T and N staging, EUS has good sensitivity and specificity.^{[5, 7]}

M staging

PET-CT is extremely useful for the detection of metastatic disease that may not be identifiable with other imaging modalities. Diagnostic-quality CT images are also useful for additional information in case of uncertainties in the PET images. Fused images are also extremely useful, again, in the localization of subtle metastases and also for guiding a potential percutaneous biopsy.

PET-CT is the gold standard for evaluation of treatment with regard to quantifying metastatic disease response. This becomes particularly important as metabolic response to chemotherapy can often outstrip physical change in the tumor. Metabolic response has been seen to correlate with the histopathologic response, and the 3-year survival is far better in responders than in nonresponders (70% vs. 35%, respectively, in a study of esophageal junction adenocarcinoma).^[12]

Pathologic staging

Histopathologic staging after surgical or endoscopic resection (Table 5) and postneoadjuvant therapy (Table 6) can be used for prognostication and guiding further management.^[13]

Table 1. TNM Classification (Open Table in a new window)

Primary tumor (T)
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	High-grade dysplasia,* defined as malignant cells confined by the basement membrane
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, azygos vein, diaphragm, or peritoneum
T4b	Unresectable tumor invading other adjacent structures, such as the aorta, vertebral body, and trachea
*High-grade dysplasia includes all noninvasive neoplastic epithelial lesions formerly called carcinoma in situ; that term is no longer used for columnar mucosae anywhere in the gastrointestinal tract.
Regional lymph nodes (N)
NX	Regional lymph node(s) cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in 1-2 regional lymph nodes
N2	Metastasis in 3-6 regional lymph nodes
N3	Metastasis in 7 or more regional lymph nodes
Distant metastasis (M)
M0	No distant metastasis
M1	Distant metastasis

Table 2. Histologic grade (Open Table in a new window)

Histologic grade (G)
GX	Grade cannot be assessed—stage grouping as G1
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated or undifferentiated*
*If undifferentiated with glandular component, stage as G3 adenocarcinoma; if undifferentiated with squamous cell component, or tumor remains undifferentiated after further testing, group as G3 squamous cell carcinoma.

Table 3. Squamous cell carcinoma location (Open Table in a new window)

X	Location unknown
Upper	Cervical esophagus to lower border of azygos vein
Middle	Lower border of azygos vein to lower border of inferior pulmonary vein
Lower	Lower border of inferior pulmonary vein to stomach, including gastroesophageal junction

Table 4. Clinical stage groups (Open Table in a new window)

Stage Group	cT	cN	cM
Squamous cell carcinoma
0	Tis	N0	M0
I	T1	N0–1	M0
II	T2	N0–1	M0
II	T3	N0	M0
III	T3	N1	M0
III	T1–3	N2	M0
IVA	T4	N0–2	M0
IVA	T1–4	N3	M0
IVB	T1–4	N0–3	M1
Adenocarcinoma
0	Tis	N0	M0
I	T1	N0	M0
IIA	T1	N1	M0
IIB	T2	N0	M0
III	T2	N1	M0
III	T3–4a	N0–1	M0
IVA	T1–4a	N2	M0
	T4b	N0–2	M0
	T1–4	N3	M0
IVB	T1–4	N0–3	M1

Table 5. Pathologic stage groups (Open Table in a new window)

Stage group	pT	pN	pM	Grade	Location
Squamous cell carcinoma
0	Tis	N0	M0	N/A	Any
IA	T1a	N0	M0	G1, X	Any
IB	T1b	N0	M0	G1–3, X	Any
	T1a	N0	M0	G2–3	Any
	T2	N0	M0	G1	Any
IIA	T2	N0	M0	G2–3, X	Any
	T3	N0	M0	Any	Lower
	T3	N0	M0	G1	Upper/middle
IIB	T3	N0	M0	G2–3	Upper/middle
	T3	N0	M0	GX	Any
	T3	N0	M0	Any	X
	T1	N1	M0	Any	Any
IIIA	T1	N2	M0	Any	Any
IIIA	T2	N1	M0	Any	Any
IIIB	T4a	N0–1	M0	Any	Any
	T3	N1	M0	Any	Any
	T2–3	N2	M0	Any	Any
IVA	T4a	N2	M0	Any	Any
	T4b	N0–2	M0	Any	Any
	T1–4	N3	M0	Any	Any
IVB	T1–4	N0–3	M1	Any	Any
Adenocarcinoma
0	Tis	N0	M0	N/A
IA	T1a	N0	M0	G1, X
IB	T1a	N0	M0	G2
IB	T1b	N0	M0	G1–2, X
IC	T1	N0	M0	G3
IC	T2	N0	M0	G1–2
IIA	T2	N0	M0	G3, X
IIB	T1	N1	M0	Any
IIB	T3	N0	M0	Any
IIIA	T1	N2	M0	Any
IIIA	T2	N1	M0	Any
IIIB	T4a	N0–1	M0	Any
	T3	N1	M0	Any
	T2–3	N2	M0	Any
IVA	T4a	N2	M0	Any
	T4b	N0–2	M0	Any
	T1–4	N3	M0	Any
	T1–4	N0–3	M1	Any
N/A = not applicable; X = not defined

Table 6. Post-neoadjuvant therapy staging (Open Table in a new window)

Stage Group	ypT	ypN	ypM
I	T0-2	N0	M0
II	T3	N0	M0
IIIA	T0-2	N1	M0
IIIB	T4a	N0	M0
	T3	N1	M0
	T0-3	N2	M0
IVA	T4a	N1-2, X	M0
	T4b	N0-2	M0
	T1-4	N3	M0
IVB	T1–4	N0–3	M1

[Guideline] NCCN Clinical Practice Guidelines in Oncology. Esophageal and Esophagogastric Junction Cancers. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. Version 2.2021 — March 9, 2021; Accessed: June 16, 2021.
American Joint Committee on Cancer. Esophagus and Esophagogastric Junction. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Manual. 8th edition. New York, NY: Springer; 2016.
DeMeester SR. Adenocarcinoma of the esophagus and cardia: a review of the disease and its treatment. Ann Surg Oncol. 2006 Jan. 13 (1):12-30. [QxMD MEDLINE Link].
Bruzzi JF, Munden RF, Truong MT, Marom EM, Sabloff BS, Gladish GW, et al. PET/CT of esophageal cancer: its role in clinical management. Radiographics. 2007 Nov-Dec. 27 (6):1635-52. [QxMD MEDLINE Link].
DaVee T, Ajani JA, Lee JH. Is endoscopic ultrasound examination necessary in the management of esophageal cancer?. World J Gastroenterol. 2017 Feb 7. 23 (5):751-762. [QxMD MEDLINE Link]. [Full Text].
Yang J, Luo GY, Liang RB, Zeng TS, Long H, Fu JH, et al. Efficacy of Endoscopic Ultrasonography for Determining Clinical T Category for Esophageal Squamous Cell Carcinoma: Data From 1434 Surgical Cases. Ann Surg Oncol. 2018 Jul. 25 (7):2075-2082. [QxMD MEDLINE Link].
ASGE Standards of Practice Committee., Jue TL, Sharaf RN, Appalaneni V, Anderson MA, Ben-Menachem T, et al. Role of EUS for the evaluation of mediastinal adenopathy. Gastrointest Endosc. 2011 Aug. 74 (2):239-45. [QxMD MEDLINE Link].
ASGE Standards of Practice Committee., Evans JA, Early DS, Chandraskhara V, Chathadi KV, Fanelli RD, et al. The role of endoscopy in the assessment and treatment of esophageal cancer. Gastrointest Endosc. 2013 Mar. 77 (3):328-34. [QxMD MEDLINE Link].
van Vliet EP, Heijenbrok-Kal MH, Hunink MG, Kuipers EJ, Siersema PD. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. 2008 Feb 12. 98 (3):547-57. [QxMD MEDLINE Link]. [Full Text].
Lerut T, Flamen P, Ectors N, Van Cutsem E, Peeters M, Hiele M, et al. Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction: A prospective study based on primary surgery with extensive lymphadenectomy. Ann Surg. 2000 Dec. 232 (6):743-52. [QxMD MEDLINE Link]. [Full Text].
Puli SR, Reddy JB, Bechtold ML, Antillon D, Ibdah JA, Antillon MR. Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review. World J Gastroenterol. 2008 Mar 14. 14 (10):1479-90. [QxMD MEDLINE Link]. [Full Text].
Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006 Oct 10. 24 (29):4692-8. [QxMD MEDLINE Link].
Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg. 2017 Mar. 6 (2):119-130. [QxMD MEDLINE Link].

Media Gallery

of 0

Table 1. TNM Classification

Primary tumor (T)
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	High-grade dysplasia,* defined as malignant cells confined by the basement membrane
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, azygos vein, diaphragm, or peritoneum
T4b	Unresectable tumor invading other adjacent structures, such as the aorta, vertebral body, and trachea
*High-grade dysplasia includes all noninvasive neoplastic epithelial lesions formerly called carcinoma in situ; that term is no longer used for columnar mucosae anywhere in the gastrointestinal tract.
Regional lymph nodes (N)
NX	Regional lymph node(s) cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in 1-2 regional lymph nodes
N2	Metastasis in 3-6 regional lymph nodes
N3	Metastasis in 7 or more regional lymph nodes
Distant metastasis (M)
M0	No distant metastasis
M1	Distant metastasis

Table 2. Histologic grade

Histologic grade (G)
GX	Grade cannot be assessed—stage grouping as G1
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated or undifferentiated*
*If undifferentiated with glandular component, stage as G3 adenocarcinoma; if undifferentiated with squamous cell component, or tumor remains undifferentiated after further testing, group as G3 squamous cell carcinoma.

Table 3. Squamous cell carcinoma location

X	Location unknown
Upper	Cervical esophagus to lower border of azygos vein
Middle	Lower border of azygos vein to lower border of inferior pulmonary vein
Lower	Lower border of inferior pulmonary vein to stomach, including gastroesophageal junction

Table 4. Clinical stage groups

Stage Group	cT	cN	cM
Squamous cell carcinoma
0	Tis	N0	M0
I	T1	N0–1	M0
II	T2	N0–1	M0
II	T3	N0	M0
III	T3	N1	M0
III	T1–3	N2	M0
IVA	T4	N0–2	M0
IVA	T1–4	N3	M0
IVB	T1–4	N0–3	M1
Adenocarcinoma
0	Tis	N0	M0
I	T1	N0	M0
IIA	T1	N1	M0
IIB	T2	N0	M0
III	T2	N1	M0
III	T3–4a	N0–1	M0
IVA	T1–4a	N2	M0
	T4b	N0–2	M0
	T1–4	N3	M0
IVB	T1–4	N0–3	M1

Table 5. Pathologic stage groups

Stage group	pT	pN	pM	Grade	Location
Squamous cell carcinoma
0	Tis	N0	M0	N/A	Any
IA	T1a	N0	M0	G1, X	Any
IB	T1b	N0	M0	G1–3, X	Any
	T1a	N0	M0	G2–3	Any
	T2	N0	M0	G1	Any
IIA	T2	N0	M0	G2–3, X	Any
	T3	N0	M0	Any	Lower
	T3	N0	M0	G1	Upper/middle
IIB	T3	N0	M0	G2–3	Upper/middle
	T3	N0	M0	GX	Any
	T3	N0	M0	Any	X
	T1	N1	M0	Any	Any
IIIA	T1	N2	M0	Any	Any
IIIA	T2	N1	M0	Any	Any
IIIB	T4a	N0–1	M0	Any	Any
	T3	N1	M0	Any	Any
	T2–3	N2	M0	Any	Any
IVA	T4a	N2	M0	Any	Any
	T4b	N0–2	M0	Any	Any
	T1–4	N3	M0	Any	Any
IVB	T1–4	N0–3	M1	Any	Any
Adenocarcinoma
0	Tis	N0	M0	N/A
IA	T1a	N0	M0	G1, X
IB	T1a	N0	M0	G2
IB	T1b	N0	M0	G1–2, X
IC	T1	N0	M0	G3
IC	T2	N0	M0	G1–2
IIA	T2	N0	M0	G3, X
IIB	T1	N1	M0	Any
IIB	T3	N0	M0	Any
IIIA	T1	N2	M0	Any
IIIA	T2	N1	M0	Any
IIIB	T4a	N0–1	M0	Any
	T3	N1	M0	Any
	T2–3	N2	M0	Any
IVA	T4a	N2	M0	Any
	T4b	N0–2	M0	Any
	T1–4	N3	M0	Any
	T1–4	N0–3	M1	Any
N/A = not applicable; X = not defined