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Esophageal Cancer Staging

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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]}

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]

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.^{[6, 7, 8, 9]}However, CT and EUS together can increase the accuracy of regional lymph node evaluation.^{[6, 10]}

For T and N staging, EUS has good sensitivity and specificity.^{[5, 6]}

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).^[11]

Histopathologic staging after surgical or endoscopic resection (Table 5) and postneoadjuvant therapy (Table 6) can be used for prognostication and guiding further management.^[12]

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

T3

N0

M0

III

T3

N1

M0

T1–3

N2

M0

IVA

T4

N0–2

M0

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

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

IIIA

T1

N2

M0

Any

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

IVB

T1–4

N0–3

M1

Any

Adenocarcinoma

0

Tis

N0

M0

N/A

IA

T1a

N0

M0

G1, X

IB

T1a

N0

M0

G2

T1b

N0

M0

G1–2, X

IC

T1

N0

M0

G3

T2

N0

M0

G1–2

IIA

T2

N0

M0

G3, X

IIB

T1

N1

M0

Any

T3

N0

M0

Any

IIIA

T1

N2

M0

Any

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. Postneoadjuvant 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 4.2017 — October 13, 2017; Accessed: February 7, 2018.

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. [Medline].

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. [Medline].

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. [Medline]. [Full Text].

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. [Medline].

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. [Medline].

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. [Medline]. [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. [Medline]. [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. [Medline]. [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. [Medline].

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. [Medline].

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

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.

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

Stage Group

cT

cN

cM

Squamous cell carcinoma

0

Tis

N0

M0

I

T1

N0–1

M0

II

T2

N0–1

M0

T3

N0

M0

III

T3

N1

M0

T1–3

N2

M0

IVA

T4

N0–2

M0

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

T3–4a

N0–1

M0

IVA

T1–4a

N2

M0

T4b

N0–2

M0

T1–4

N3

M0

IVB

T1–4

N0–3

M1

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

IIIA

T1

N2

M0

Any

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

IVB

T1–4

N0–3

M1

Any

Adenocarcinoma

0

Tis

N0

M0

N/A

IA

T1a

N0

M0

G1, X

IB

T1a

N0

M0

G2

T1b

N0

M0

G1–2, X

IC

T1

N0

M0

G3

T2

N0

M0

G1–2

IIA

T2

N0

M0

G3, X

IIB

T1

N1

M0

Any

T3

N0

M0

Any

IIIA

T1

N2

M0

Any

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

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

Anand D Patel, MD Hematologist/Oncologist, Ascension Wisconsin

Anand D Patel, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Student National Medical Association