Purpose: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). Methods: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. Results: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. Conclusions: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

1.
Klöppel
G
,
Perren
A
,
Heitz
PU
.
The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification
.
Ann N Y Acad Sci
.
2004
Apr
;
1014
(
1
):
13
27
.
[PubMed]
0077-8923
2.
Dasari
A
,
Shen
C
,
Halperin
D
,
Zhao
B
,
Zhou
S
,
Xu
Y
, et al
Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States
.
JAMA Oncol
.
2017
Oct
;
3
(
10
):
1335
42
.
[PubMed]
2374-2437
3.
Rindi
G
,
Arnold
R
,
Bosman
FT
, et al
 Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In:
Bosman
FT
, editor
.
WHO classification of tumours of the digestive system
. 4th ed.
Lyon, France
:
IARC Press
;
2010
. p.
64
.
4.
Rindi
G
,
Klöppel
G
,
Alhman
H
,
Caplin
M
,
Couvelard
A
,
de Herder
WW
, et al;
all other Frascati Consensus Conference participants
;
European Neuroendocrine Tumor Society (ENETS)
.
TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system
.
Virchows Arch
.
2006
Oct
;
449
(
4
):
395
401
.
[PubMed]
0945-6317
5.
Xie
JW
,
Sun
YQ
,
Feng
CY
,
Zheng
CH
,
Li
P
,
Wang
JB
, et al
Evaluation of clinicopathological factors related to the prognosis of gastric neuroendocrine carcinoma
.
Eur J Surg Oncol
.
2016
Oct
;
42
(
10
):
1464
70
.
[PubMed]
0748-7983
6.
Yao
JC
,
Hassan
M
,
Phan
A
,
Dagohoy
C
,
Leary
C
,
Mares
JE
, et al
One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States
.
J Clin Oncol
.
2008
Jun
;
26
(
18
):
3063
72
.
[PubMed]
0732-183X
7.
Amin
MB
,
Edge
SB
,
Greene
FL
, et al
AJCC Cancer Staging Manual
. 8th ed.
New York
:
Springer
;
2016
.
8.
Kubota
T
,
Ohyama
S
,
Hiki
N
,
Nunobe
S
,
Yamamoto
N
,
Yamaguchi
T
.
Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute
.
Gastric Cancer
.
2012
Jul
;
15
(
3
):
323
30
.
[PubMed]
1436-3291
9.
Shia
J
,
Tang
LH
,
Weiser
MR
,
Brenner
B
,
Adsay
NV
,
Stelow
EB
, et al
Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity?
Am J Surg Pathol
.
2008
May
;
32
(
5
):
719
31
.
[PubMed]
0147-5185
10.
Dasari
A
,
Mehta
K
,
Byers
LA
,
Sorbye
H
,
Yao
JC
.
Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: A SEER database analysis of 162,983 cases
.
Cancer
.
2018
Feb
;
124
(
4
):
807
15
.
[PubMed]
0008-543X
11.
Sun
Z
,
Wang
ZN
,
Zhu
Z
, et al
Evaluation of the seventh edition of American Joint Committee on Cancer TNM staging system for gastric cancer: results from a Chinese monoinstitutional study. Ann Surg Oncol 19:1918-27,
2012
12.
Han
DS
,
Suh
YS
,
Kong
SH
,
Lee
HJ
,
Choi
Y
,
Aikou
S
, et al
Nomogram predicting long-term survival after d2 gastrectomy for gastric cancer
.
J Clin Oncol
.
2012
Nov
;
30
(
31
):
3834
40
.
[PubMed]
0732-183X
13.
Yoon
HM
,
Ryu
KW
,
Nam
BH
,
Cho
SJ
,
Park
SR
,
Lee
JY
, et al
Is the new seventh AJCC/UICC staging system appropriate for patients with gastric cancer?
J Am Coll Surg
.
2012
Jan
;
214
(
1
):
88
96
.
[PubMed]
1072-7515
14.
Heagerty
PJ
,
Lumley
T
,
Pepe
MS
.
Time-dependent ROC curves for censored survival data and a diagnostic marker
.
Biometrics
.
2000
Jun
;
56
(
2
):
337
44
.
[PubMed]
0006-341X
15.
Sorbye
H
,
Strosberg
J
,
Baudin
E
,
Klimstra
DS
,
Yao
JC
.
Gastroenteropancreatic high-grade neuroendocrine carcinoma
.
Cancer
.
2014
Sep
;
120
(
18
):
2814
23
.
[PubMed]
0008-543X
16.
Chen
ZH
,
Xing
L
,
Min
D
, et al
Comparison of a new prognostic system and five current staging systems in predicting the survival rate of patients with advanced hepatocellular carcinoma
.
J Clin Oncol
.
2014
;
32
3_suppl
:
e193
193
. 0732-183X
17.
Lin
JX
,
Lin
JP
,
Li
P
,
Xie
JW
,
Wang
JB
,
Lu
J
, et al
Which staging system better predicts 10-year survival for gastric cancer? A study using an international multicenter database
.
Eur J Surg Oncol
.
2018
Aug
;
44
(
8
):
1205
11
.
[PubMed]
0748-7983
18.
Sano
T
,
Coit
DG
,
Kim
HH
,
Roviello
F
,
Kassab
P
,
Wittekind
C
, et al
Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project
.
Gastric Cancer
.
2017
Mar
;
20
(
2
):
217
25
.
[PubMed]
1436-3291
19.
Kulke
MH
.
Are neuroendocrine tumors going mainstream?
J Clin Oncol
.
2013
Feb
;
31
(
4
):
404
5
.
[PubMed]
0732-183X
20.
Strosberg
JR
,
Weber
JM
,
Feldman
M
,
Coppola
D
,
Meredith
K
,
Kvols
LK
.
Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors
.
J Clin Oncol
.
2013
Feb
;
31
(
4
):
420
5
.
[PubMed]
0732-183X
21.
Kim
MK
,
Warner
RR
,
Roayaie
S
,
Harpaz
N
,
Ward
SC
,
Itzkowitz
S
, et al
Revised staging classification improves outcome prediction for small intestinal neuroendocrine tumors
.
J Clin Oncol
.
2013
Oct
;
31
(
30
):
3776
81
.
[PubMed]
0732-183X
22.
Warneke
VS
,
Behrens
HM
,
Hartmann
JT
, et al
Cohort study based on the seventh edition of the TNM classification for gastric cancer: proposal of a new staging system. J Clin Oncol 29:2364-71,
2011
23.
Zhang
J
,
Niu
Z
,
Zhou
Y
,
Cao
S
. A comparison between the seventh and sixth editions of the American Joint Committee on Cancer/International Union Against classification of gastric cancer. Ann Surg 257:81-6,
2013
24.
Park
JY
,
Ryu
MH
,
Park
YS
,
Park
HJ
,
Ryoo
BY
,
Kim
MG
, et al
Prognostic significance of neuroendocrine components in gastric carcinomas
.
Eur J Cancer
.
2014
Nov
;
50
(
16
):
2802
9
.
[PubMed]
0959-8049
25.
Collins
GS
,
de Groot
JA
,
Dutton
S
,
Omar
O
,
Shanyinde
M
,
Tajar
A
, et al
External validation of multivariable prediction models: a systematic review of methodological conduct and reporting
.
BMC Med Res Methodol
.
2014
Mar
;
14
(
1
):
40
.
[PubMed]
1471-2288
26.
Fang
C
,
Wang
W
,
Feng
X
,
Sun
J
,
Zhang
Y
,
Zeng
Y
, et al
Nomogram individually predicts the overall survival of patients with gastroenteropancreatic neuroendocrine neoplasms
.
Br J Cancer
.
2017
Nov
;
117
(
10
):
1544
50
.
[PubMed]
0007-0920
27.
Steyerberg
EW
,
Harrell
FE
 Jr
.
Prediction models need appropriate internal, internal-external, and external validation
.
J Clin Epidemiol
.
2016
Jan
;
69
:
245
7
.
[PubMed]
0895-4356
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.