Introduction

INTRODUCTION

Gastric cancer represents the third leading cause of cancer mortality worldwide, with an estimated incidence of 951,000 cases, causing 723,000 deaths annually.¹ The American Cancer Society estimates that in the United States in 2017, 28,000 cases of gastric cancer will be diagnosed, and 10,960 men and women will die from the disease.² More than 70% of new cases arise in the developing world, and despite an overall decline in age-adjusted incidence, absolute incidence is increasing because the proportion of the population that is older and more likely to be diagnosed is increasing. Host risk factors in the United States include being male, being older, and not being white.³ Established behavioral risk factors include Helicobacter pylori infection, smoking, Epstein-Barr virus infection, and consumption of foods high in salt or N-nitroso compounds, such as those in processed or smoked meats.⁴ Gastric cancer incidence appears to be increasing in younger age groups; however, the cause of this phenomenon is not yet clear.⁵

The cornerstone of curative-intent treatment for gastric adenocarcinoma is complete surgical resection, including an adequate regional lymphadenectomy.⁶,⁷,⁸,⁹,¹⁰,¹¹ However, multimodality therapy (including perioperative chemotherapy¹² and radiation¹³) is integral to maximizing the possibility of long-term survival. This approach likely will be even more pronounced as novel therapies in treating metastatic gastric adenocarcinoma (including targeted therapy¹⁴ and immunotherapy¹⁵) are employed in neoadjuvant and adjuvant settings.

The definition of the term complete surgical resection, perhaps surprisingly, is not universally agreed upon by experts in the field. The disputes include differences over the definition of an adequate margin of resection, the definition of an adequate lymphadenectomy, and the necessity of resecting adjacent organs (i.e., performing splenectomy). Several studies addressing these issues have produced conflicting results, which have further fueled debates.¹⁶,¹⁷,¹⁸,¹⁹ Compounding the issue is the somewhat unique factor of “East versus West” in gastric adenocarcinoma: Many studies of more aggressive surgery that have been of benefit in Asian studies have not been reproducible in European and North American studies. Often, the lack of benefit in the Western series is attributable to increased morbidity and mortality.²⁰,²¹,²²,²³ Furthermore, there may be pathophysiologic differences between gastric adenocarcinoma in the East and West.²³,²⁴,²⁵

Irrespective of these debates, gastric adenocarcinoma continues to be a significant clinical problem. When it is identified early, prior to a high likelihood of metastasis, surgery is often curative. However, when tumors deeply invade the stomach and metastasize to regional lymph nodes, recurrence is common and nearly always fatal. This fact has led the oncology community to attempt to identify gastric cancers at high risk of metastasis preoperatively and treat them with neoadjuvant regimens. Similarly, patients whose high-risk tumors are detected at surgery are prescribed adjuvant treatments postoperatively.

STAGING

The eighth edition of the AJCC Cancer Staging Manual was published by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control
in 2017.²⁶ The major changes between this and previous editions were predominantly focused on stage III disease in order to stratify survival better on differing degrees of nodal involvement. Disease is stratified into seven risk groups according to pathologic depth of invasion and the number of metastatic lymph nodes.²⁶ What is important is that the N staging system of the eighth edition requires for optimal performance that at least 15 lymph nodes must be harvested. This requirement provides improvement in the stated goals of the AJCC cancer staging system: monotonicity (decreased survival with increasing stage), distinctiveness (difference in survival among groups), and homogeneity (similar survival within each group). The major changes in the N groups between the seventh and eighth editions include the placement of some disease staged as pN3a into stage IIIB and some disease staged pT3-4N3b as IIIC (Table I-1).

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

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

Category	Criteria
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria, high-grade dysplasia
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 penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures^,^*
T4	Tumor invades the serosa (visceral peritoneum) or adjacent structures^,^*
T4a	Tumor invades the serosa (visceral peritoneum)
T4b	Tumor invades adjacent structures/organs
^A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified as T3. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified as T4. ^The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. ^**Intramural extension to the duodenum or esophagus is not considered invasion of an adjacent structure, but is classified using the depth of the greatest invasion in any of these sites.