Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors

Abstract

Purpose Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3–20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. Methods Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. Results A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3–9%) and G2 high (Ki67 10–20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. Conclusion Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.

Outlook for 615 Small Intestinal Neuroendocrine Tumor Patients: Recurrence Risk after Surgery and Disease-Specific Survival in Advanced Disease

“…Therefore, our data question the value of the current grading system that uses a Ki-67 cut-off of 3% as a prognostic tool. A study from 2023 has displayed significant differences in overall survival and RFS between NET G2 divided into low (3–9%) grade and high (10–20%) grade [ 14 ]. Other previous studies have suggested that a cut-off level of 5% provides better prognostic information [ 8 , 13 ].…”

“…Due to the slow growth of the tumor, recurrence may occur many years after the surgery [ 12 , 13 ]. Risk factors for disease recurrence include disease stage and proliferation index [ 12 , 13 , 14 ]. If radical surgery is not possible, systemic therapy with somatostatin analogues (SSA) is recommended as the first-line treatment in low-grade tumors.…”

Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine

“…For example, tumor stage, tumor grading, carcinoid disease and carcinoid heart disease are well-established risk factors for reduced overall survival [15][16][17][18]. Focusing on tumor recurrence and disease progression, multiple tumor manifestations, lymph node and distant metastases, tumor size and grading are confirmed negative predictors [19][20][21]. Consistent with previous findings [15,22], the risk for disease recurrence or progression in our cohort was lower when curative surgery could be achieved: while 54.0% of the whole cohort experienced postoperative disease progression, disease recurrence was observed in only 15.1% of the curatively resected patients.…”