Introduction

INTRODUCTION

Esophageal cancer remains one of the more challenging solid tumors to treat, because it responds only modestly to chemotherapy and radiation and requires extremely complex surgery for resection and restoration of gastrointestinal continuity. Esophageal cancer is the eighth most common malignancy and the sixth most common cause of cancerrelated death in the world. The incidence of esophageal cancer has increased dramatically over the past three decades and affects more than 450,000 people worldwide.¹

In the United States, approximately 17,000 patients will be diagnosed with esophageal cancer in 2017, and an estimated 15,690 will die; overall, the disease is associated with an expected 5-year survival rate of 18%.² Multimodality strategies, prompted by poor results with surgery alone, have aimed at improving the survival of patients with localized disease. However, significant areas of discussion and controversy exist.

This chapter will help to elucidate and provide pointed recommendations to optimize the intraoperative treatment of resectable esophageal cancer so as to enhance positive outcomes as part of a comprehensive multimodality approach.

DIAGNOSIS AND CLINICAL STAGING

The diagnosis of esophageal cancer is typically made with esophagogastroscopy. A tissue biopsy is critical to rational decision-making, as is an assessment of the tumor’s size, its location within the esophagus (upper 18 to 24 cm, middle 24 to 32 cm, or lower 32 to 40 cm), and its distance relative to the gastroesophageal junction and the upper esophageal sphincter. Whether there is extension into the stomach must also be determined prior to initiating therapy.

A detailed computed tomography scan of the chest and abdomen with oral and intravenous contrast is essential to evaluate for the proximity/invasion of adjacent structures and vessels. Concern for aortic invasion may call for the addition of a magnetic resonance imaging. Employment of a positron emission tomography scan or positron emission tomography/computed tomography can help to elucidate the presence or absence of metastatic disease. An endoscopic ultrasonography (EUS) study should be performed to provide the most accurate tumor depth information (T stage), for localized assessment of lymph nodes (N stage), and to assess the need for potential biopsy of clinically suspicious lymph nodes. Despite its current role, EUS has been shown to be inaccurate for T-staging, resulting in up- and down-staging of tumors.³ As such, endomucosal resection (EMR) is frequently used as a staging modality for superficial tumors that appear to be ≤T1 in depth by EUS—if the tumor is T1a, EMR may also provide definitive treatment given the low associated incidence of nodal metastasis.

Staging for esophageal cancer changed with the seventh edition of the staging manual by the American Joint Committee on Cancer and the Union for International Cancer Control, which separated algorithms for adenocarcinoma and squamous cell carcinoma and included histologic grade. With the new eighth edition, the staging of esophageal cancers was further affected by the Worldwide Esophageal Cancer Collaboration, which provided data on more than 22,000 patients, of whom 13,300 had received no preoperative therapy.⁴ An updated staging system table from the American Joint Committee on Cancer eighth edition is provided in Tables I-1 and I-2.

TABLE I-1 American Joint Committee on Cancer Staging Criteria for Esophageal Cancer, 8^th Edition

TABLE I-1A Definition of Primary Tumor (T)

All Carcinomas
Category	Criteria
TX	Tumor cannot be assessed
T0	No evidence of primary tumor
Tis	High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane
T1	Tumor invades the lamina propria, muscularis mucosae, or submucosa
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

TABLE I-1B Definition of Regional Lymph Node (N)

All Carcinomas
Category	Criteria
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in one or two regional lymph nodes
N2	Metastasis in three to six regional lymph nodes
N3	Metastasis in seven or more regional lymph nodes

TABLE I-1C Definition of Distant Metastasis (M)

All Carcinomas
Category	Criteria
M0	No distant metastasis
M1	Distant metastasis

TABLE I-1D Definition of Histologic Grade (G)

Squamous Cell Carcinoma and Adenocarcinoma
G	G Definition
GX	Grade cannot be assessed
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated, undifferentiated

TABLE I-1E Definition of Location (L)

Squamous Cell Carcinoma
Location plays a role in the stage grouping of esophageal squamous cancers.
Category	Criteria
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
Note: Location is defined by the position of the epicenter of the tumor in the esophagus.

TABLE I-1F AJCC Prognostic Stage Groups-Esophageal Cancer

Squamous Cell Carcinoma

In addition to anatomic tumor depth, nodal status, and metastasis (see Definitions of AJCC TNM), other prognostic factors – grade (G) and location (L) – affect outcome, and therefore staging, of squamous cell carcinoma.

TABLE I-1F-1 Clinical (cTNM)

When cT is…	And cN is…	And M is…	Then the stage group is…
Tis	N0	M0	0
T1	N0-1	M0	I
T2	N0-1	M0	II
T3	N0	M0	II
T3	N1	M0	III
T1-3	N2	M0	III
T4	N0-2	M0	IVA
Any	T	N3	M0	IVA
Any T	Any N	M1	IVB

TABLE I-1F-2 Pathological (pTNM)

When pT is…	And pN is…	And M is	And G is…	And location is…	Then the stage group is…
Tis	N0	M0	N/A	Any	0
T1a	N0	M0	G1	Any	IA
T1a	N0	M0	G2-3	Any	IB
T1a	N0	M0	GX	Any	IA
T1b	N0	M0	G1-3	Any	IB
T1b	N0	M0	GX	Any	IB
T2	N0	M0	G1	Any	IB
T2	N0	M0	G2-3	Any	IIA
T2	N0	M0	GX	Any	IIA
T3	N0	M0	G1-3	Lower	IIA
T3	N0	M0	G1	Upper/middle	IIA
T3	N0	M0	G2-3	Upper/middle	IIB
T3	N0	M0	GX	Lower/upper/middle	IIB
T3	N0	M0	Any	Location X	IIB
T1	N1	M0	Any	Any	IIB
T1	N2	M0	Any	Any	IIIA
T2	N1	M0	Any	Any	IIIA
T2	N2	M0	Any	Any	IIIB
T3	N1-2	M0	Any	Any	IIIB
T4a	N0-1	M0	Any	Any	IIIB
T4a	N2	M0	Any	Any	IVA
T4b	N0-2	M0	Any	Any	IVA
Any T	N3	M0	Any	Any	IVA
Any T	Any N	M1	Any	Any	IVB