Lymphadenectomy with Optimum of 29 Lymph Nodes Retrieved Associated with Improved Survival in Advanced Gastric Cancer: A 25,000-Patient International Database Study

Abstract

Background Gastric adenocarcinoma is an aggressive disease with frequent lymph node (LN) metastases for which lymphadenectomy results in a survival benefit. In the United States, the NCCN guidelines recommend D2 lymphadenectomy or a minimum of 15 LNs retrieved. However, retrieval of only 15 LNs is considered by most international guidelines as inadequate. We seek to evaluate the survival benefits associated with a more complete lymphadenectomy. Study Design An international database was constructed by combining gastric cancer cases from the SEER database (n=13,932) and the Yonsei University Gastric Cancer database (n=11,358)(total n=25,289). Kaplan-Meier survival analysis was performed along with Joinpoint analysis to obtain the optimal number of LNs to retrieve based upon survival. Prognostic significance of number of nodes retrieved was then confirmed with uni- and multivariate analyses. Results Analysis for both mean and median survival yielded 29 LNs removed as the Joinpoint. This was further confirmed with multivariate analysis, where 15 retrieved LNs cutoff fell out of the model while 29 retrieved LNs remained intact with an hazard ratio (HR): 0.799(95%CI 0.759–0.842, p<0.001). Stage-stratified Kaplan- Meier analysis for a cutoff point of 29 also demonstrated a statistically significant improvement in survival. Conclusion Joinpoint analysis has allowed for the creation of a model demonstrating the point at which additional dissection would not provide further benefit. Thus, this large international dataset analysis demonstrates that the maximal survival advantage is seen by performing a lymphadenectomy with a minimum of 29 LNs retrieved.

Multi‐institutional validation of the 8th AJCC TNM staging system for gastric cancer: Analysis of survival data from high‐volume Eastern centers and the SEER database

“…Ignoring N3b classification might be suitable for patients with limited lymph node dissection and inspection, thereby limiting the number of lymph nodes retrieved. However, many investigators, including those in Western countries, are considering that D2 lymph node dissection, permitting the retrieval of a greater number of lymph nodes, and thorough assessment of lymph nodes could reduce stage migration effects and lay the groundwork for precise staging . Accordingly, many studies have raised the need for revised stratification …”

“…The time periods over which the data were collected differed among the datasets (SH, January 1987 to December 2013; GSH, January 1987 to December 2008; SEER, January 2002 to December 2012). Data from the SEER database were searched and extracted, as described previously . This retrospective study was approved by the Institutional Review Board of Severance Hospital, Yonsei University College of Medicine (2018‐1097‐001).…”

The Methods of Lymph Node Examination Make a Difference to Node Staging and Detection of N3b Node Status for Gastric Cancer

“…Recently, Hayashi et al showed that the number of RLNs < 40 could be attributed to an inferior survival for stage III gastric cancer (GC) patients who underwent total gastrectomy (2). Consistently, another large international dataset analysis, including the SEER database (n = 13,932) and the Yonsei University Gastric Cancer database (n = 11,358), also proposed that a greater number of RLNs (a minimum of 29) improves staging and OS in GC patients undergoing radical resection (3). All of these quality studies proposed a higher number of RLNs than that recommended by the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for GC (at least 16).…”

“…Many studies have suggested that overall survival (OS) is associated with the number of retrieved lymph nodes (RLNs) (1)(2)(3). The results based on data from the Surveillance, Epidemiology, and End Results (SEER) database showed that OS was dependent on the number of RLNs (1).…”

Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institution dataset

“…Woo et al [23] used the Surveillance, Epidemiology, and End Results (SEER) program's database and the Korean database to an analysis of 25,289 patients with gastric cancer [23]. This analysis demonstrates that the maximum survival advantage was achieved by performing a lymphadenectomy with a minimum of 29 RLNs [25]. However, these studies are limited by the inconsistent content of the data that include mixed types of gastrectomy, varying extents of lymphadenectomies, and broad disease stages, which likely lead to potential selection bias.…”