New TNM  in the Staging of Gastric Cancer

Dongfeng Tan, MD

Introduction

Properly staging cancer allows the clinician to choose the appropriate treatment modalities, reliably evaluate and predict outcomes of disease management, and uniformly document cancer cases worldwide. Although there are several classification systems for gastric cancer, the Cancer Staging Manual developed by the American Joint Committee on Cancer (AJCC) with support from International Union for Cancer Control (UICC), the American Cancer Society, American College of Surgeons, American Society of Clinical Oncology, and International Union against Cancer, is the generally accepted classification system. The cancer-staging criteria have been continually refined since 1959, with the combined efforts of medical community, and multiple medical and oncology organizations. The latest edition (7^th edition) of the AJCC Cancer Staging Manual was published in early 2010. In the new edition, the AJCC and UICC used large datasets and emerging evidence to support changes in the cancer staging criteria in general, and they used data sets from Asia, Europe, and the United States for the gastric cancer staging systems in particular.

In the new edition of the AJCC staging manual, tumors arising at the EGJ, or arising within the proximal 5 cm of the stomach (cardia) that extends into the EGJ or esophagus, are staged using the TNM system for adenocarcinoma of the esophagus. All other cancers with a midpoint in the stomach lying more than 5 cm distal to the EGJ, or those within 5 cm of the EGJ but not extending into the EGJ or esophagus, are staged using the gastric cancer staging system.

DEFINITIONS OF TNM

TNM staging describes three major anatomic characteristics of cancer: 1) the location and extension of the primary tumor, 2) the presence or absence of lymph node involvement, and 3) the presence or absence of distant tumor metastasis. These features can be evaluated by physical examination, imaging studies, and histopathologic evaluation. All cancers, though, should be confirmed histologically.

Before pathologic staging, efforts should be made to differentiate primary gastric cancer from metastatic disease, which is not an uncommon event. After the primary gastric cancer is established, gastric cancer should be classified. Majority of gastric cancer is adenocarcinoma. The histological subtypes of gastric cancer are listed in Table 1. 

            Adenocarcinoma (more than 90%)

            Adenosquamous carcinoma

            Mucinous adenocarcinoma

            Papillary adenocarcinoma

            Signet ring cell carcinoma

            Squamous cell carcinoma

            Tubular adenocarcinoma

Pathologically, the extent of the tumor needs to be carefully assessed. Pathologic staging depends on data acquired clinically together with findings on subsequent gross and microscopic examination of the surgically resected specimen.

Of note, the TNM staging recommendations apply only to carcinomas. Lymphomas, sarcomas, and carcinoid tumors (well-differentiated neuroendocrine tumors) are excluded. Mixed glandular/neuroendocrine carcinomas should be staged using the gastric carcinoma staging system for well-differentiated gastrointestinal neuroendocrine tumors.

Designation of primary gastric cancer status     

Staging of primary gastric adenocarcinoma is dependent on the extension and depth of penetration of the primary tumor. Histologically, the wall of the stomach has five layers: mucosa, submucosa, muscular propria, subserosal connective tissue, and serosal surface.

One of the major changes to the T designation for gastric cancer in the 7^th edition of the AJCC Cancer Staging Manual is that the T categories have been modified to correspond to the T categories for cancers of the esophagus and small and large intestine. Specifically, T1 lesions have been subdivided into T1a and T1b, which are defined as tumor invades muscularis mucosae and tumor invades submucosa, respectively; T2 is defined as a tumor that invades the muscularis propria; T3 is defined as a tumor that invades the subserosal connective tissue (formerly T2b in AJCC Cancer Staging Manual, 6^th edition); and T4 is defined as a tumor that invades the serosa (visceral peritoneum, formerly T3 in AJCC Cancer Staging Manual, 6^th edition) or adjacent structures. The T (primary tumor) designation of gastric cancer is listed in Table 2.

Table 2.    Primary Tumor (T) of Gastric Cancer

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TX        Primary tumor cannot be assessed

T0        No evidence of primary tumor

Tis       Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria

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 penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures *

T4        Tumor invades serosa (visceral peritoneum) or adjacent structures *

T4a       Tumor invades serosa (visceral peritoneum)

T4b       Tumor invades adjacent structures

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*The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum.

Designation of regional lymph node status

The regional lymph nodes of the stomach are roughly divided into two major groups: 1) the perigastric nodes, which include nodes in the greater curvature of the stomach and nodes in the lesser curvature of the stomach, and 2) the local nodes in the pancreatic and splenic area.

Adequate dissection of these regional nodal areas is important to ensure the appropriate pN designations and final staging. For pathologic assessment, the regional lymph nodes are removed and examined histologically to evaluate the total number of lymph nodes as well as the number that contain metastatic tumors. N categories have been modified in the new AJCC staging manual, with N1=1-2 positive regional lymph nodes, N2=3-6 positive regional lymph nodes (N1 in the 6^th edition of AJCC staging manual) and N3=7 or more positive regional lymph nodes. In addition, metastatic nodules in the fat adjacent to a gastric carcinoma, without evidence of residual lymph node tissue, are considered regional lymph node metastases. Although it has been suggested that pathologists assess at least 16 regional lymph nodes, a pN determination may be assigned on the basis of the actual number of nodes evaluated microscopically. The N (regional lymph node) designation of gastric cancer is listed in Table 3.

Table 3.  Regional Lymph Nodes (N) of Gastric Cancer

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NX       Regional lymph node(s) cannot be assessed

N0       No regional lymph node metastasis*

N1       Metastasis in 1-2 regional lymph nodes

N2       Metastasis 3-6 regional lymph nodes

N3       Metastasis in seven or more regional lymph nodes

N3a      Metastasis in 7-15 regional lymph nodes

N3b      Metastasis in 16 or more regional lymph nodes

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*Note: A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.

Designation of distant metastasis status:

Two designations of metastatic status are included in the 7^th edition of the AJCC Cancer Staging Manual, namely, M0: No distant metastasis, and

M1:Distant metastasis. Note, no Mx designation was mentioned in the 7^th edition of the AJCC Cancer Staging Manual.

Distant metastasis means that the tumor has disseminated to distant lymph nodes or a distant organ system.    The distant lymph nodes of gastric cancer include retropancreatic, hepatoduodenal, para-aortic, portal, retroperitoneal, and mesenteric. Involvement of these intra-abdominal lymph nodes is classified as distant metastasis. Other metastatic sites include distant organs (liver, lungs, and central nervous system) and peritoneal surfaces (tumor implants). Positive peritoneal cytology is now classified as metastatic disease (M1). A summary of designation of distal metastatic tumor is listed in Table 4.

Metastatic carcinoma in distant lymph nodes

                  Hepatoduodenal

                  Mesenteric

                  Para-aortic

                  Portal

                  Retropancreatic

                  Retroperitoneal

Metastatic carcinoma in distant organs

                  Liver

                  Lungs

                  CNS

                  Other less common organ sites

Metastatic carcinoma in peritoneal surfaces

DESIGNATION OF ANATOMIC STAGE

The final grouping (staging) of gastric cancer is dependent on the appropriate designations of T, N, and M.  The anatomic stage, based on the current AJCC Cancer Staging Manual, is listed in Table 5. Of note, if there is uncertainty concerning the appropriate T, N, or M designation, the lower (less advanced) category should be assigned, in accordance with the general rules of staging.

Table 5   Anatomic Stage of Gastric Cancer*

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Stage 0                                     Tis                                N0                               M0

Stage IA                                   T1                                N0                               M0

Stage IB                                   T2                                N0                               M0

                                                T1                                N1                               M0

Stage IIA                                 T3                                N0                               M0

                                                T2                                N1                               M0

                                                T1                                N2                               M0

Stage IIB                                  T4a                              N0                               M0

                                                T3                                N1                               M0

                                                T2                                N2                               M0

                                                T1                                N3                               M0

Stage IIIA                                T4a                              N1                               M0

                                                T3                                N2                               M0

                                                T2                                N3                               M0

Stage IIIB                                T4b                              N0                               M0

                                                T4b                              N1                               M0

                                                T4a                              N2                               M0

                                                T3                                N3                               M0

Stage IIIC                                T4b                              N2                               M0

                                                T4b                              N3                               M0                  

                                                T4a                              N3                               M0

Stage IV                                  

   Any T                           Any N                          M1

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* from the AJCC Cancer Staging Manual, 7^th Edition.