Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors

Abstract

BACKGROUND. Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a rare but challenging group of malignant neoplasms and occur at virtually any site of the GEP system. In 2006, a new TNM classification system was proposed for the staging and grading of upper GEP NETs. METHODS. The prognostic relevance of the TNM classification system was analyzed retrospectively in 202 patients from a referral center with histologically proven foregut NET. Patients were classified according to previous classification systems and the TNM classification. Survival data were acquired and statistical analyses were performed by using log‐rank and Cox regression testing. RESULTS. Primary tumors were gastric (n = 48), duodenal (n = 23), and pancreatic (n = 131). During the observation period, 21% of patients died. The overall 5‐ and 10‐year survival rates were 75% and 64%, respectively. Previous classification systems discriminated between low‐grade and high‐grade malignant NETs but did not allow further prognostic differentiation. In contrast, the proposed TNM classification was able to differentiate significantly between different tumor stages (stages I‐III vs stage IV; P < .01) and cellular proliferation rates according to Ki‐67 labeling (grade 1 vs grade 2, P = .04; grade 1 vs grade 3 and grade 2 vs grade 3, P < .01). Cox regression analysis confirmed an increased risk of reduced survival for patients with stage III or IV NET and grade 2 or 3 NET. CONCLUSIONS. The current results demonstrated the prognostic relevance of the newly proposed TNM classification system for foregut NETs with statistical significance for the subgroups of both the staging classification and the grading system. Thus, the new classification system provides a valid and powerful tool for prognostic stratification of GEP NETs in clinical practice and research. Cancer 2008. © 2008 American Cancer Society.

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

“…[16][17][18][19] Ekeblad et al 16 reported the analysis of 324 pancreatic endocrine tumors for which diagnosis according to WHO was available in only 241, whereas TNM data were available for 302 and grading for 93 patients. The study did not show any difference between stages I vs II or III, and only demonstrated a significant difference between stage IV (metastatic disease) vs any stage.…”

“…This resulted in a significant drop of survival after about 10 years for the WHO category of well-differentiated endocrine tumors in a disease for which only 70% of deaths are expected to be disease-related. 19 Moreover, grading resulted significant only if poorly differentiated endocrine carcinomas were included.…”

“…15 The validation of these TNM and grading systems has been variably addressed in four recent studies that all evidenced clear-cut distinctions only between higher and lower stages while they were of little help for intermediate-stage diseases. [16][17][18][19] There is clearly the need of a system permitting the prognostic stratification of all pancreatic endocrine tumor patients, including both those who may benefit from radical surgery and those with more advanced disease that cannot be resected.…”

GEP-NETs update: Functional localisation and scintigraphy in neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP-NETs)

“…According to the current WHO grading system, GEP-NETs can be classified according to their Ki-67 proliferation index (MIB-1 staining) into grade 1 (G1), with a Ki-67 index amounting to, or !2%, G2 with a Ki-67 index between 3 and 20% and G3 with a Ki-67 index higher then 20% (4,5). Grading correlates well with the clinical course of patients harbouring these GEP-NETs (6,7,8,9). In addition, clinical features such as the primary localisation of these GEP-NETs, the secretion of excessive amounts of hormones or peptides by these GEP-NETs and the metastatic spread, as reflected by staging of these GEP-NETs, also determine their clinical manifestations and contribute to their prognosis (1,10,11).…”

Behavior of small, asymptomatic, nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs)

“…Other authors suggest that surgery is indicated in any case because NF-PNETs should always be considered as potentially malignant tumors, and a proper histological examination of the tumor (including the mitotic and Ki-67 indexes) is possible only on the resected specimen. 21,22 Previous studies have reported that several factors are associated with survival, including age, 23,24 tumor size, 9,23,[25][26][27] grade/differentiation, 14,24,25,28 LN status, 25,29 presence of distant metastases, 14,23,24,29 and surgical resection. 14,23 Age has consistently been found to be a powerful predictor of survival in patients undergoing resection of PNETs.…”