Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors.
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.
Department of Hepatology and Gastroenterology, Chariteé-Campus Virchow Clinic, Berlin University of Medicine, Berlin, Germany. ulrich-frank.pape@charite.de
Ulrich-Frank
UF
Pape
Henning
H
Jann
Jacqueline
J
Müller-Nordhorn
Angelina
A
Bockelbrink
Uta
U
Berndt
Stefan N
SN
Willich
Martin
M
Koch
Christoph
C
Röcken
Guido
G
Rindi
Bertram
B
Wiedenmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000145:classification* / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000145:classification* / Q000453:epidemiology / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000145:classification* / Q000453:epidemiology / Q000473:pathology*; D011379:Prognosis; D012307:Risk Factors; D017678:Sex Distribution; D015996:Survival Rate; D014944:World Health Organization