Prognostic value of metastatic lymph node ratio as an additional tool to the TNM stage system in gastric cancer

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Abstract

Background

Gastric cancer is one of most common malignancies in the world. Currently the prognostic prediction is entirely based on the TNM staging system. In this study, we evaluated whether metastatic lymph node ratio (rN) at the time of surgery would improve the prognostic prediction in conjunction with the TNM staging system.

Methods

This retrospective study includes 745 patients, who had been referred for surgery due to gastric cancer between 1995 and 2007 and had at least 15 lymph nodes examined at the time of surgery without preoperative treatment. Clinicopathologic features and overall survival were analyzed using univariate and multivariate modes to identify the risk factors for overall survival.

Results

Median overall survival of all patients analyzed is 57.8 months and 5-year overall survival is 49.5%. Tumor site, macroscopic type, pTNM stage, and rN stage are identified as independent prognostic factors. Increased positive lymph node ratio correlates with shorter survival in all patients and in each T and N stage. In stage III gastric cancer patients, rN stage shows additional prognostic value on overall survival (p < 0.001).

Conclusions

rN stage is a simple and promising prognostic factor of gastric cancer after surgery in addition to the TNM stage system especially in stage III patients. But the independent prognostic value of rN stage in stage I, II and IV gastric cancer is yet to be determined.

Introduction

Gastric cancer is a common solid malignancy in the world, with especially high incidence in the Eastern Asia. It is estimated that 952,000 new cases of gastric cancer, representing 6.8% of the total cancer were diagnosed in the world in 2012, making it the fifth most common malignancy and the third leading cause of death due to cancer.1, 2 The goal of staging for gastric cancer is to predict the prognosis of the patients. The depth of tumor invasion (T) and nodal involvement (N) are currently the most important prognostic factors in surgically treatable gastric cancer.3, 4, 5 A good staging system was defined as reflecting “decreased patient survival with increasing stage group, difference in survival between groups, and similar survival with in a group”.6 Nowadays, the most commonly used staging system for gastric cancer is the TNM system established collaboratively by American Joint Committee on Cancer (AJCC) and the International Union for Cancer Control (UICC). This TNM system stratifies patients on the basis of depth of primary invasion (T), number of metastatic positive lymph nodes (N), and presence of distant metastasis (M).7, 8 The 7th edition AJCC TNM stage system requires a minimum of 15 lymph nodes to be examined to determine the N stage. Specifically N1 refers to cases with 1–2 metastatic nodes. N2 refers to cases with 3–6 nodes and N3 with more than 6 nodes (N3a with 7–15 nodes, N3b with ≥16 nodes).8

In addition to the TNM staging system, alternative N staging system exists and one of the most promising one is the metastatic lymph node ratio (rN) which is defined as the ratio between the positive lymph nodes and the number of lymph nodes examined. Recently, several studies have evaluated the prognostic value of rN stage in gastric cancer and most of the studies concluded that the rN stage had better prognostic value than the traditional N stage in the TNM system.9, 10, 11, 12, 13, 14, 15 But the majority of these studies only evaluate the rN stage in patients with less than 15 lymph nodes examined. While rN stage proved to be useful for patients with insufficient lymph node examined, the prognostic value of rN in patients with >15 lymph nodes tested has not been compared with TNM system.9, 11, 13, 15

In this study, we investigated the prognostic value of the rN stage in patients with >15 lymph nodes examined and evaluated the rN stage as an independent prognostic factor for gastric cancer patients with curative resection and the possibility of rN stage as an additional tool to the 7th edition TNM stage system.

Section snippets

Study design and patients

All patients with gastric cancer surgically treated at Peking University Cancer Hospital from November 1995 to March 2007 were enrolled in this retrospective study. The inclusion criteria include: (1) pathologically-proved adenocarcinoma; (2) tumors arising in the distal stomach or arising in the proximal 5 cm but not crossing the esophagogastric junction as required by the 7th edition of the AJCC cancer staging manual16; (3) patients received radical gastrectomy with at least 15 lymph nodes

Patients characteristics

The demographic features and the tumor characteristics of the 745 patients included in this study are listed in Table 1. Among all the tumors, 44.4% were located in the lower third of the stomach and 19.7% were in the upper third. Early gastric cancer accounts for <10% and locally advanced gastric cancer accounts for 79.0%. A total of 42.7% (n = 318) patients received postoperative chemotherapy. The median number of lymph nodes examined is 22 (range 15–71) and the average metastasis positive

Discussion

Gastric cancer is one of the most common malignant tumor in the world. How to predict the prognosis after surgery is one of the most important questions to be answered. The TNM staging system is currently the most widely used nomograph to predict the survival of gastric cancer patients. The metastatic lymph node status is one of the major parameters.

The N stage in the TNM staging system is based on the number of metastatic lymph nodes and is a powerful prognostic factor. A minimum number of 15

Conflict of interest

No commercial conflicts of interest is involved in the subject of study.

Disclosure

Xiao-Jiang Wu and other co-authors have no commercial conflicts of interest in the subject of study.

Acknowledgment

Supported by Open Fund of Key Laboratory of Carcinogenesis, 2015 Ministry of Education (1122-02-1402).

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    These authors are contributed equally to this study.

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