New lymph node staging for rectal neuroendocrine tumors

Abstract

Background and Objectives: Current guidelines of the American Joint Commission on Cancer (AJCC) for rectal neuroendocrine tumors (NETs) classify tumor nodal status as N0/N1. This staging does not take into consideration the number of positive lymph nodes. The goal of this study is to determine how the number of positive lymph nodes affects the prognosis for patients with rectal NETs. Methods: The National Cancer Database was used to identify patients with rectal NETs who underwent rectal resection. Nearest-neighborhood grouping was used to classify patients by survival to create a new nodal staging system. Results: There were 687 patients with rectal NETs. There were distinct 5-year survival estimates for patients with N0 [81.8% (95%CI:77.1%-85.6%)], N1 (1-4 positive lymph nodes) [57.8% (95% confidence interval (CI: 51.2%-63.9%)] and N2 (≥5 positive lymph nodes) [32.6% (95%CI:25.1%-40.3%)] patients, P < 0.0001. Distinct 5-year survival estimates using the new nodal staging system was apparent for patients in the external validation set. After adjusting for predictors of survival in multivariable analysis, the new nodal stage remained an independent predictor of overall survival. Conclusions: The number of positive locoregional lymph nodes is an independent prognostic factor in rectal NETs. The next AJCC edition should consider classifying patients with rectal NETs as N0, N1, and N2 to provide better estimates of survival for patients. K E Y W O R D S AJCC staging, carcinoid tumor, lymph nodes, rectal cancer, rectal neuroendocrine tumor 1 | INTRODUCTION Gastroenteropancreatic neuroendocrine tumors (NETs) have varied behaviors and prognoses depending on their location in the gastrointestinal tract. The rectum is one of the most common sites of gastrointestinal NETs with an age-adjusted incidence of approximately 1 per 100,000. 1,2 Furthermore, the incidence of rectal NETs has increased tenfold over the past 30 years. 3 Tumor size, depth of invasion, and lymph node status are important prognostic factors. 4-6 The five-year survival after diagnosis with rectal NETs is typically higher than other NET sites and exceeds 88%. 4 This is likely due to tumors being localized at the time of diagnosis. 2 Once rectal NETs metastasize, however, five-year survivaldrops to 36%-73% in the presence of regional lymph node metastasis and to 15%-30% for distant metastasis. 2,7,8 In 2010, the American Joint Commission on Cancer (AJCC) published its first TNM staging classification for rectal NETs; locoregional lymph node metastases were characterized as present or absent (N1/N0) and continue to be characterized in this system in the 2017 AJCC 8th edition. 9 This staging system matches the classification developed by the European Neuroendocrine Tumor Society (ENETS) and North American Neuroendocrine J Surg Oncol. 2019;119:156-162. wileyonlinelibrary.com/journal/jso 156 |

A novel preoperative risk score to predict lymph node positivity for rectal neuroendocrine tumors: An NCDB analysis to guide operative technique

“…Among nonfunctional rectal neuroendocrine tumors, the association between nodal involvement and poor outcomes has been clearly established with a recent study demonstrating worse survival with an increasing number of positive lymph nodes. 27,28 The current study supports these previous findings, with node-positive patients displaying a three-fold hazard ratio for overall survival compared to node-negative patients even when accounting for other negative prognostic factors.…”

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database

“…On further analysis, only T4 stage, tumors > 2 cm, poorly differentiated tumors, and metastatic disease were independent prognostic factors. Unlike previous reports, [ 2 , 13 , 14 ] we did not find LN involvement to be an independent prognostic factor, although it was associated with worse survival on univariate analysis.…”

Case report: Coexistence of sigmoid tumor with unusual pathological features and multiple colorectal neuroendocrine tumors with lymph node metastases

“…Such conclusions indicate that the neuroendocrine component of these special tumors is most likely to be the primary cause of malignancy and should be considered when deciding the appropriate treatment. According to a recent large study ( 16 ), there is a significant survival difference among rectal neuroendocrine neoplasm patients with zero positive lymph node, one to four positive lymph nodes, and ≥5 positive lymph nodes. This conclusion should be taken into account when deciding the appropriate treatment of tumors containing neuroendocrine components.…”