Prognostic Role of Lymph Node Positivity and Number of Lymph Nodes Needed for Accurately Staging Small-Bowel Neuroendocrine Tumors

Abstract

IMPORTANCE Little information is available regarding the minimum number of lymph nodes needed to accurately stage patients when performing a mesenteric lymphadenectomy for small-bowel neuroendocrine tumors. OBJECTIVES To determine the prognostic role of lymph node positivity and the ideal number of lymph nodes for accurately staging patients with small-bowel neuroendocrine tumors. DESIGN, SETTING, AND PARTICIPANTS This case series from the US Neuroendocrine Tumor Study Group, a collaboration among 8 US-based, academic tertiary care referral centers, obtained demographic, perioperative, and pathologic data from the group's database, Social Security Death Index, and publicly available obituaries. All patients in these institutions with small-bowel neuroendocrine tumors who underwent curative-intent surgical resection of a primary tumor between January 1, 2000, and December 31, 2015, were included (n = 199). Patients with duodenal or ampullary tumors, other nonneuroendocrine concurrent malignant neoplasms, mortality of fewer than 30 days after the surgical procedure, and distant metastatic disease were excluded. Data analysis was conducted from September 1, 2017, to December 1, 2017. MAIN OUTCOMES AND MEASURES Primary study outcome was recurrence-free survival. Hypothesis was generated after data collection and data entry into the US Neuroendocrine Tumor Study Group database. RESULTS Of the 199 patients included, 112 (56.3%) were male and 87 (43.7%) female with a mean (SD) age of 60.3 (12.5) years and a mean (SD) body mass index of 29.5 (6.0). One hundred fifty-four patients (77.4%) had lymph node-positive disease. No difference in 3-year recurrence-free survival was found between patients with lymph node-positive and lymph node-negative disease. Patients with 4 positive lymph nodes had a worse 3-year recurrence-free survival compared with those with 1 to 3 or 0 positive lymph nodes (81.6% vs 91.4% vs 92.1%; P = .01). When examining patients with fewer than 8 resected lymph nodes, no difference in 3-year recurrence-free survival was observed among patients with 4 or more, 1 to 3, or 0 positive lymph nodes (100% vs 93.8% vs 91.7%; P = .87). Retrieval of 8 or more lymph nodes, however, accurately discriminated patients with 4 or more, 1 to 3, or 0 positive lymph nodes (3-year recurrence-free survival: 79.9% vs 89.6% vs 92.9%; P = .05). CONCLUSIONS AND RELEVANCE The findings from this study suggest that, for patients undergoing curative-intent resection of small-bowel neuroendocrine tumors, accurate lymph node staging requires a minimum of 8 lymph nodes for examination, and 4 or more positive lymph nodes are associated with decreased 3-year recurrence-free survival compared with 1 to 3 or 0 positive lymph nodes; a thorough regional lymphadenectomy may be critical for accurate staging and management of this disease.

Duodenal neuroendocrine tumors: Impact of tumor size and total number of lymph nodes examined

“…In fact, TNLE among patients with pancreatic and small bowel NETs relative to recurrence-free survival and overall survival has been examined by our group and others. 15,24 Using a large multi-institutional database with external validation based on the surveillance, epidemiology, and end results (SEER) registry, we demonstrated that TNLE ≥ 8 had the highest discriminatory power relative to recurrence-free and overall survival among patients with pNET who hadone to three LNM, and patients who had ≥4 LNM in both a multi-institutional data set and the SEER database. 15 In the current study, we similarly noted that TNLE ≥ 8 had the strongest discriminatory power to ensure identification of possible LNM and optimally stage the nodal basin for patients with dNETs.…”

Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity?

“…The impact of lymph node positivity in neuroendocrine tumors also may not be uniform across all disease sites. Our group recently reported that there is limited prognostic significance of lymph node positivity in small bowel neuroendocrine tumors if fewer than 4 lymph nodes are positive . It is important to note that the average number of positive lymph nodes in this study was 3.4 and 3.8 in small bowel neuroendocrine tumors for Black and White race patients, respectively.…”

Albumin to alkaline phosphatase ratio: does it predict survival in grade 1 and grade 2 neuroendocrine tumors?

“…In the literature, there are many studies aiming to define prognostic or predictive markers in this heterogeneous group of tumor (4-7). Primary tumor site, stage, grade, age, primary tumor size and lymph node involvement have been shown to predict disease outcome in previous studies (8,9). Of these factors, grade and are the most reliable prognostic parameters and stage strongly correlate with survival (10,11).…”