Original Article

Increased Survival Associated With Surgery and Radiation

Therapy in Metastatic Gastric Cancer
A Surveillance, Epidemiology, and End Results Database Analysis
Ravi Shridhar, MD, PhD1; Khaldoun Almhanna, MD2; Sarah E. Hoffe, MD1; William Fulp, MPH3; Jill Weber, MPH2;
Michael D. Chuong, MD1; and Kenneth L. Meredith, MD2

BACKGROUND: Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes
of metastatic gastric cancer patients stratified by surgery and radiation therapy. METHODS: The Surveillance, Epidemiology, and
End Results (SEER) database was accessed to identify patients with AJCC M1 stage IV gastric cancer (based on the American
Joint Committee on Cancer Cancer Staging Manual, 6th edition) between 2004 thru 2008. Patients were divided into 4 groups:
group 1, no surgery or radiation; group 2, radiation alone; group 3, surgery alone; group 4, surgery and radiation. Survival analysis
was determined by Kaplan-Meier and log-rank analysis. Multivariate analysis (MVA) was analyzed by the Cox proportional hazard
ratio model. RESULTS: A total of 5072 patients were identified. Surgery and/or radiation were associated with a survival benefit.
Median and 2-year survival for groups 1, 2, 3, and 4 was 7 months and 8.2%, 8 months and 8.9%, 10 months and 18.2%, and 16
months and 31.7%, respectively (P < .00001). MVA for all patients revealed that surgery and radiation were associated with
decreased mortality whereas T-stage, N-stage, age, signet ring histology, and peritoneal metastases were associated with
increased mortality. In patients treated with surgery, MVA showed that radiation was associated with decreased mortality,
whereas T-stage, N-stage, age, removal of < 15 lymph nodes, signet ring histology, and peritoneal metastases was associated
with increased mortality. Age was the only prognostic factor in patients who did not undergo surgery. CONCLUSIONS: Surgery
and radiation are associated with increased survival in a subset of patients with metastatic gastric cancer. Prospective trials will
be needed to address the role and sequence of surgery and radiation in metastatic gastric cancer. Cancer 2013;119:163642.
C 2013 American Cancer Society.
V
KEYWORDS: metastatic gastric cancer, gastrectomy, radiation, survival, Surveillance, Epidemiology, and End Results.

INTRODUCTION
Gastric cancer is the second leading cause of cancer mortality and the fourth most common cancer in the world with
approximately 934,000 new cases diagnosed and an anticipated 700,000 deaths annually.1 In the United States, an estimated 21,000 new cases and 11,000 deaths were expected in 2010.2 However, most gastric cancers are diagnosed at
advanced or metastatic stages when the tumor is considered unresectable.3 Several phase 3 randomized control trials of various chemotherapy regimens in metastatic gastric cancer have shown median survivals ranging from 7.9 to 13.8 months.4
There are few reports on the role of locoregional therapy in the management of metastatic gastric cancer. Small retrospective series have suggested a survival benefit to palliative resections.5-7 Although radiation therapy has been shown to be
effective at palliating pain, obstruction, and bleeding from gastric tumors, there have been no reports on a potential survival benefit in metastatic gastric cancer.8-13
Several studies have been published concerning outcomes of radiation and surgery in the setting of localized gastric
cancer from the Surveillance, Epidemiology, and End Results (SEER) database. However, there has been only one report
on the outcomes of metastatic gastric cancer from SEER, and it did not discuss the role of radiation and surgery in the
management of metastatic gastric cancer.14 In the current report, we present data on outcomes of metastatic gastric cancer
patients treated between 2004 and 2008 who were treated with or without surgery and radiation therapy. This is the first
report of its kind from the SEER database.

Corresponding author: Ravi Shridhar, MD, PhD, Department of Radiation Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612; Fax: (813)
745-7231; Ravi.Shridhar@moffitt.org
1
Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida; 2Gastrointestinal Tumor Program, Moffitt Cancer Center, Tampa, Florida; 3Biostatistics
Core, Moffitt Cancer Center, Tampa, Florida

DOI: 10.1002/cncr.27927, Received: August 3, 2012; Revised: November 13, 2012; Accepted: November 13, 2012, Published online January 29, 2013 in Wiley
Online Library (wileyonlinelibrary.com)

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Surgery, Radiation, and M1 Gastric Cancer/Shridhar et al

MATERIALS AND METHODS

Patients

Data were obtained from the SEER Limited Access database. Using the SEER 17 Registries, the 2008 release of the
public-use data set 2004-2008 was queried to determine
metastatic gastric cancer patients who did or did not
undergo surgery and/or radiation therapy. Patients included
in the analysis were aged 18 years or older, had American
Joint Committee on Cancer (AJCC), 6th edition,15 stage
IV (M1) disease, were treated with or without postoperative
or preoperative external beam radiation therapy, and had
histologic subtypes of adenocarcinoma (not otherwise specified [NOS], intestinal-type, mucinous or mucin-producing,
mixed cell or with mixed subtypes, in adenoma or polyp,
and with neuroendocrine differentiation) or carcinoma
(NOS, diffuse type, and signet ring cell). Patients were
excluded from the analysis if they had < 3 months survival,
received intraoperative radiation, radioimplants, radioisotopes, if radiation status was unknown, if surgery status was
unknown, and if they had histologic subtypes of squamous
cell carcinoma, carcinoid, neuroendocrine tumor, small cell
carcinoma, leiomyosarcoma, sarcoma, gastrointestinal stromal sarcoma, clear cell adenocarcinoma, adenosquamous
carcinoma, melanoma, carcinosarcoma, rhabdoid tumors,
and malignant peripheral nerve sheet tumors. Surgical
patients underwent some form of gastrectomy with or without a lymph node dissection. Our initial query of M1 gastric cancer patients between 2004 and 2008 that were ! 18
years of age identified 8978 patients. After excluding
patients with based on histology, 8409 patients remained.
There were 3337 patients with < 3 months survival
excluded from the analysis. The vast majority of these
patients did not receive any locoregional therapy. Of these
3337 patients with < 3 months survival, 2750 patient did
not receive radiation or surgery, 241 patients were treated
with radiation alone, 330 patients treated with surgery
alone, and 16 patients were treated with both surgery and
radiation. These patients were excluded to weed out poorly
performing patients who were probably not healthy enough
to receive any therapy that could dramatically impact the
analysis in favor of locoregional therapy.
Data not included in the SEER database include
patient comorbidities, nutritional status, performance status, surgical margin status, postoperative complications,
type of lymphadenectomy, chemotherapy and radiation
dose, and field design.
Statistical Analysis

The variable radiation/surgery status consisted of 4 levels:

patients who did not receive radiation or surgery, patients
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May 1, 2013

treated with radiation alone, patients treated with surgery

alone, and patients who were treated with both surgery
and radiation. Descriptive statistics were presented overall
and by radiation/surgery status. Comparisons between
radiation/surgery status and demographic characteristics
were made using the exact Wilcoxon rank-sum test for
continuous characteristics, and the exact Pearson chisquare test for categorical characteristics, both using
Monte Carlo estimation. Overall survival was examined
using Kaplan-Meier survival curves with log-rank test.
Multivariate analysis (MVA) of prognostic factors related
to survival (radiation therapy, AJCC T-stage, number of
lymph nodes removed, AJCC N-Stage, surgery, tumor
location, histologic subtype, and tumor grade) was performed by the Cox proportional hazard model. All P values are 2-sided and considered statistically significant at
the .05 level. All statistical analyses were performed using
SAS (version 9.3; SAS Institute, Cary, NC).
RESULTS
We identified 5072 patients who met inclusion criteria.
There were 3069 patients who did not receive radiation or
surgery (group 1), 806 patients treated with radiation
alone (group 2), 957 patients treated with surgery alone
(group 3), and 240 patients treated with surgery and radiation (group 4). Patient characteristics are presented in
Table 1.
The overall survival (OS) for the 4 groups of patients
listed above is displayed in Figure 1. Radiation and surgery were associated with increased survival. Median and
2-year OS for groups 1, 2, 3, and 4 was 7 months and
8.2%, 8 months and 8.9%, 10 months and 18.2%, and
16 months and 31.7%, respectively (log-rank P <
.00001). All curves were statistically significant from one
another (Fig. 1A). When patients with survival of < 3
months were included in the analysis, median and 2-year
OS for groups 1, 2, 3, and 4 was 4 months and 5.1%, 6
months and 7.3%, 8 months and 14.9%, and 15 months
and 31.2%, respectively (log-rank P < .00001) and all
curves were statistically significant from one another (Fig.
1B). Given that majority of patients with < 3 months survival had not received radiation or surgery, we decided to
proceed with rest of the analysis excluding those patients.
Multivariate analysis for all patients revealed that
surgery (hazard ratio [HR] 0.565; 95% CI 0.4950.645; P < .0001) and radiation (HR 0.882; 95% CI
0.781-0.995; P .042) were associated with decreased
mortality (Table 2). Increasing age, T4 tumors, N3 nodes,
signet ring histology, and peritoneal carcinomatosis were
associated with increased mortality. Sex, tumor grade, and
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Original Article
TABLE 1. Patient Characteristics
N (%)
Variable

No Surg/No RT

No Surg/RT

Surg/No RT

Surg/RT

N
Mean age (# SD)
Sex
Female
Male
Year of diagnosis
2004
2005
2006
2007
2008
Metastases at diagnosis
Distant nodes
Carcinomatosis or NOS
Both
Tumor location
Cardia
Fundus
Body
Antrum
Pylorus
Lesser curve
Greater curve
Overlapping site
NOS
Tumor histology
AC NOS
Signet ring carcinoma
Carcinoma
Mucinous AC
Mixed cell AC
Linitis plastica
AJCC T-stageb
T0
T1
T2
T3
T4
Tx
AJCC N-stageb
N0
N1
N2
N3
Nx
Grade
Well
Moderate
Poor
Undifferentiated
Unknown

3069
62.8 (14.7)

806
63.5 (13.1)

957
63.9 (14.2)

240
60 (13)

1206 (39.3%)
1863 (60.7%)

195 (24.2%)
611 (75.8%)

400 (41.8%)
557 (58.2%)

74 (30.8%)
166 (69.2%)

619
578
643
704
525

172
149
160
193
132

206
212
228
184
127

58
50
52
47
33

Pa

0.0012
<.0001

0.0164
(20.2%)
(18.8%)
(21%)
(22.9%)
(17.1%)

(21.3%)
(18.5%)
(19.9%)
(23.9%)
(16.4%)

(21.5%)
(22.2%)
(23.8%)
(19.2%)
(13.3%)

(24.2%)
(20.8%)
(21.7%)
(19.6%)
(13.8%)
<.0001

2282 (74.4%)
487 (15.9%)
300 (9.8%)

511 (63.4%)
159 (19.7%)
136 (16.9%)

743 (77.6%)
92 (9.6%)
122 (12.7%)

136 (56.7%)
21 (8.8%)
83 (34.6%)

853 (27.8%)
154 (5%)
313 (10.2%)
430 (14%)
60 (2%)
165 (5.4%)
96 (3.1%)
301 (9.8%)
697 (22.7%)

507 (62.9%)
24 (3%)
38 (4.7%)
53 (6.6%)
9 (1.1%)
21 (2.6%)
17 (2.1%)
53 (6.6%)
84 (10.4%)

112 (11.7%)
28 (2.9%)
96 (10%)
243 (25.4%)
36 (3.8%)
115 (12%)
69 (7.2%)
132 (13.8%)
126 (13.2%)

86 (35.8%)
6 (2.5%)
21 (8.8%)
57 (23.8%)
10 (4.2%)
16 (6.7%)
5 (2.1%)
12 (5%)
27 (11.3%)

1900 (61.9%)
233 (7.6%)
33 (1.1%)
41 (1.3%)
64 (2.1%)
798 (26%)

609 (75.6%)
52 (6.5%)
7 (0.9%)
5 (0.6%)
19 (2.4%)
114 (14.1%)

505 (52.8%)
66 (6.9%)
23 (2.4%)
30 (3.1%)
31 (3.2%)
302 (31.6%)

151 (62.9%)
21 (8.8%)
3 (1.3%)
7 (2.9%)
12 (5%)
46 (19.2%)

6 (0.2%)
498 (16.2%)
338 (11%)
181 (5.9%)
641 (20.9%)
1405 (45.8%)

2 (0.2%)
168 (20.8%)
91 (11.3%)
86 (10.7%)
160 (19.9%)
299 (37.1%)

1 (0.1%)
41 (4.3%)
312 (32.6%)
300 (31.3%)
277 (28.9%)
26 (2.7%)

0 (0%)
11 (4.6%)
102 (42.5%)
65 (27.1%)
52 (21.7%)
10 (4.2%)

976 (31.8%)
905 (29.5%)
14 (0.5%)
8 (0.3%)
1166 (38%)

232 (28.8%)
354 (43.9%)
6 (0.7%)
4 (0.5%)
210 (26.1%)

128 (13.4%)
356 (37.2%)
255 (26.6%)
176 (18.4%)
42 (4.4%)

36 (15%)
114 (47.5%)
54 (22.5%)
29 (12.1%)
7 (2.9%)

51 (1.7%)
516 (16.8%)
1677 (54.6%)
49 (1.6%)
776 (25.3%)

17 (2.1%)
190 (23.6%)
414 (51.4%)
19 (2.4%)
166 (20.6%)

9 (0.9%)
140 (14.6%)
716 (74.8%)
39 (4.1%)
53 (5.5%)

4 (1.7%)
44 (18.3%)
157 (65.4%)
11 (4.6%)
24 (10%)

<.0001

<.0001

<.0001

<.0001

<.001

P values were calculated using the exact Wilcoxon rank-sum test for continuous characteristics, and the exact Pearson chi-square test for categorical characteristics, both using Monte Carlo estimation.
b
American Joint Committee on Cancer (AJCC) stage determined by the 6th edition.15Abbreviations: AC, adenocarcinoma; NOS, not otherwise specified; RT,
radiation therapy; SD, standard deviation; Surg, surgery.

tumor location were not prognostic for survival. MVA for

patients who underwent surgical resection showed that
radiation (HR 0.733; 95% CI 0.592-0.907; P
.004) was associated with decreased mortality, whereas
1638

increasing age, removal of < 15 lymph nodes, tumor

stage, nodal stage, signet ring histology, and peritoneal
carcinomatosis conferred higher mortality. There was a
trend toward higher mortality as tumor and nodal stage
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Surgery, Radiation, and M1 Gastric Cancer/Shridhar et al

Figure 1. Kaplan-Meier analysis is shown of overall survival of

metastatic gastric cancer patients stratified by radiation
(rads) and surgical (surg) resection. (A) Curves are shown for
a set of 5072 patients with ! 3 months survival. All curves
are statistically significant from one another (log-rank P <
.00001). (B) A larger set of 8409 patients included patients
with < 3 months survival. All curves are statistically significant from one another (log-rank P < .00001).

increased. Sex, tumor location, and tumor grade were not

prognostic for survival (Table 2). In patients who did not
undergo surgical resection, MVA demonstrated that only
increasing age was prognostic for higher mortality. There
was a trend for worse mortality with signet ring histology.
Sex, radiation, tumor stage, nodal stage, tumor location,
tumor histology, tumor grade, and peritoneal carcinomatosis were not prognostic for survival (Table 2).
DISCUSSION
This is the first report to suggest that surgery and radiation
are associated with increased survival in metastatic gastric
cancer. On univariate Kaplan-Meier analysis, patients
who received radiation had a higher survival over patients
not treated with radiation therapy, which was confirmed
by MVA except in nonsurgical patients. Surgery also was
associated with increased survival both on univariate and
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May 1, 2013

multivariate analysis. Interestingly, removal of > 15

lymph nodes, which has been shown to be associated with
increased survival in the nonmetastatic setting,16,17 was
associated with higher survival, whereas there was a trend
for worse survival with higher tumor and nodal stage. The
location of metastases also affected survival. Patients with
peritoneal carcinomatosis had worse survival compared
with patients who had distant lymph node metastases.
Signet ring histology also conferred worse outcomes. Sex,
tumor location, and grade did not impact survival in metastatic gastric cancer.
Although systemic chemotherapy is by far the most
effective modality for increasing survival in metastatic gastric cancer, it is not that effective in relieving symptoms of
obstruction, pain, and bleeding caused by the primary tumor. Local treatment modalities such as partial gastrectomy, radiation therapy, or both are far more effective at
managing symptoms caused by the primary tumor.
Although radiation therapy has been shown to be effective
at palliating pain, obstruction, and bleeding from gastric
tumors, there have been no reports on a potential survival
benefit in metastatic gastric cancer.8-13 There are studies
of chemoradiation in the locally advanced setting that
show a significant survival benefit. An early Mayo Clinic
study randomized 48 patients with unresectable disease to
concurrent chemoradiation with 35-40 Gy of supervoltage radiation and 5-fluorouracil.18 Median survival
favored chemoradiation (13 months versus 6 months)
with a 5-year OS of 12% for patients treated with chemoradiation. A North Central Cancer Treatment Group trial
evaluated the role of 5-fluorouracil based chemoradiation
with doses ranging from 45-54 Gy in unresectable gastrointestinal carcinomas.19 Included in the analysis were 6
gastric cancer patients, of whom 2 had no evidence of disease 38 to 50 months after completion of treatment.
Palliative gastrectomy has been associated with
increased survival in patients with advanced gastric cancer.5,6 Meijer et al6 showed that in 51 patients who underwent palliative resection or bypass, patients who
underwent resection had prolonged survival (9.5 months
versus 4.2 months) compared with patients who had gastric bypass. Similarly, a report from Bozzetti et al
attempted to stratify patients with metastatic gastric cancer by disease extent.5 The median survival was higher for
patients undergoing palliative resection compared with
those who had bypass, exploratory laparotomy only, or no
surgery at all (8 versus 3.5, 2.8, and 2.4 months, respectively). After stratification by disease extent, the survival
advantage of palliative resection was still maintained.
Suzuki et al reported on a trial from 2001 to 2009, where
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Original Article
TABLE 2. Multivariate Analysis for Overall Survival
All Patients

HR

95% CI

1.01
1.05
0.565
0.882

1.006-1.013
0.946-1.166
0.495-0.645
0.781-0.995

<.0001
0.362
<.0001
0.042

1.031
1.063
1.183

0.885-1.202
0.904-1.251
1.026-1.363

0.696
0.458
0.021

1.018
1.202
1.272

0.905-1.144
0.999-1.447
1.032-1.567

0.769
0.052
0.024

1.085
1.259
1.35

0.757-1.556
0.884-1.793
0.873-2.089

0.655
0.202
0.177

1.329
1.398

1.032-1.567
1.169-1.671

<.0001
<.0001

0.941
0.975
1.034
0.895
0.902
1
0.976

0.791-1.119
1.749-1.268
0.867-1.240
0.643-1.245
0.770-1.298
0.802-1.186
0.757-1.556

0.49
0.847
0.694
0.51
0.361
1
0.805

0.875
0.968
1.218
0.979
1.143

0.624-1.227
0.782-1.198
1.073-1.381
0.719-1.332
0.773-1.690

0.439
0.764
0.002
0.891
0.503

HR

95% CI

1.01
1.151
0.733
1.239

1.003-1.016
0.986-1.343
0.592-0.907
1.031-1.490

0.001
0.075
0.004
0.022

1.707
1.778
2.093

1.062-2.744
1.098-2.878
1.292-3.389

0.027
0.019
0.003

1.182
1.444
1.593

0.920-1.519
1.102-1.891
1.149-2.208

0.191
0.008
0.005

0.829
0.909
1.021

0.439-1.565
0.489-1.169
0.501-2.079

0.562
0.762
0.955

1.543
1.793

1.240-1.920
1.314-2.447

<.0001
<.0001

1.104
1.043
1.075
0.801
1.039
0.951
1.088

0.824-1.480
0.665-1.636
0.827-1.397
0.507-1.265
0.763-1.414
0.662-1.367
0.813-1.456

0.506
0.855
0.588
0.341
0.807
0.788
0.57

TABLE 2. Multivariate Analysis for Overall Survival

(Continued)
All Patients

Agea
Sex (vs male)
Surgery (vs none)
Radiation (vs none)
T-stage (vs T1)
T2
T3
T4
N-stage (vs N0)
N1
N2
N3
Grade (vs well)
Moderate
Poor
Anaplastic
Location of mets (vs nodes)
Peritoneal
Peritoneal and nodes
Site (vs Body)
Cardia
Fundus
Antrum
Pylorus
Lesser curve
Greater curve
Overlap
Histology (vs AC NOS)
Mixed AC
Carcinoma
Signet ring
Mucinous AC
Linitis plastica

Surgery-Only Patients
a

Age
Sex (vs male)
Radiation (vs none)
LN removed (vs !15)
T-stage (vs T1)
T2
T3
T4
N-stage (vs N0)
N1
N2
N3
Grade (vs well)
Moderate
Poor
Anaplastic
Location of mets (vs nodes)
Peritoneal
Peritoneal and nodes
Site (vs body)
Cardia
Fundus
Antrum
Pylorus
Lesser curve
Greater curve
Overlap

(Continued)
1640

Histology (vs AC NOS)

Mixed AC
Carcinoma
Signet ring
Mucinous AC
Linitis plastica

Nonsurgical Patients
Agea
Sex (vs male)
Radiation (vs none)
T-stage (vs T1)
T2
T3
T4
N-stage (vs N0)
N1
N2
N3
Grade (vs well)
Moderate
Poor
Anaplastic
Location of mets (vs nodes)
Peritoneal
Peritoneal and nodes
Site (vs body)
Cardia
Fundus
Antrum
Pylorus
Lesser curve
Greater curve
Overlap
Histology (vs AC NOS)
Mixed AC
Carcinoma
Signet ring
Mucinous AC
Linitis plastica

HR

95% CI

1.085
1.065
1.229
0.868
1.23

0.697-1.688
0.779-1.457
1.021-1.480
0.586-1.285
0.709-2.133

HR

95% CI

1.009
0.992
0.987

1.004-1.014
0.858-1.147
0.847-1.149

<.0001
0.91
0.863

1.043
0.966
1.097

0.864-1.260
0.782-1.192
0.936-1.287

0.659
0.745
0.253

0.976
0.691
0.944

0.851-1.119
0.342-1.367
0.388-2.296

0.73
0.303
0.899

1.18
1.442
1.389

0.757-1.838
0.932-2.229
0.778-2.479

0.465
0.1
0.267

1.132
1.162

0.936-1.369
0.932-1.450

0.202
0.183

0.871
0.948
1.046
0.963
0.771
1.153
0.877

0.696-1.090
0.680-1.321
0.808-1.353
0.589-1.574
0.547-1.087
0.775-1.715
0.667-1.153

0.226
0.751
0.734
0.881
0.138
0.481
0.347

0.68
0.903
1.187
1.161
1.022

0.395-1.171
0.670-1.218
0.995-1.415
0.694-1.943
0.581-1.800

0.164
0.505
0.056
0.571
0.939

0.719
0.692
0.029
0.48
0.462

Continuous variable.Abbreviations: AC, adenocarcinoma; CI, confidence

interval; HR, hazard ratio; LN, lymph node; mets, metastases; NOS, not
otherwise specified.

stage IV gastric cancer patients were treated with S-1/cisplatin or S-1/docetaxel chemotherapy.7 Adjuvant surgery
of the primary and metastatic disease was performed on
37 patients. Surgical patients had a median survival of
855 days versus 277 days for those without an operation
(P < .0001). In the Dutch Gastric Cancer Trial, 26% of
the randomized patients were found to have incurable
tumors at laparotomy, including unresectable tumor or
metastases to liver, peritoneum, or distant lymph nodes.20
The patients underwent an explorative laparotomy, a gastroenterostomy, or a partial or total gastrectomy. For
patients undergoing resection, median OS was greater
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Surgery, Radiation, and M1 Gastric Cancer/Shridhar et al

compared with patients who were not resected (8.1

months versus 5.4 months; P < .001). The benefit was
maintained in patients > 70 years, however there was a
significant increase in perioperative mortality (50% versus
20%). In patients with one metastatic lesion, a significant
survival benefit was noted in patients who underwent
resection (median survival of 10.5 months versus 6.7
months; P .034), but the benefit was lost if more than
one metastasis was noted (median survival of 5.7 months
versus 4.6 months; P .084).
There are currently 2 prospective trials being conducted to address the role of palliative surgery in stage IV
gastric cancer.7 The REGATTA trial being conducted in
Japan and Korea will address the role of palliative surgery
followed by chemotherapy in metastatic gastric cancer. In
Japan, a phase 2/3 trial about to be conducted will treat
patients with S-1 and docetaxel or cisplatin. Those patients
achieving a partial or complete response will be randomized
to either continued chemotherapy or will undergo surgical
resection followed by additional chemotherapy.7
Other tumor sites have shown increased survival
with the addition of locoregional therapy (LRT) in the
treatment of metastatic disease.21-23 Nguyen et al reported
on the outcomes of 733 metastatic breast cancer patients
treated between 1996 and 2004 who underwent LRT
with either surgery, radiation, or both from the British
Columbia Cancer Agency.24 The 5-year OS for patients
who had LRT was 21% compared with 14% for those
patients not treated with LRT (P < .001). The survival
benefit of LRT was also confirmed on MVA (HR 0.78;
95% CI 0.64-0.94; P .009). Two randomized trials
confirmed the benefit of surgery in metastatic renal cell
carcinoma.21,22 A study by Flanigan et al21 showed that
metastatic patients who underwent radical nephrectomy
followed by interferon had a median OS of 11.1 months
compared with 8.1 months for patients treated with interferon alone (P .05). Mikisch et al showed that in
patients with metastatic kidney cancer, nephrectomy followed by interferon resulted in a median survival of 17
months compared with 7 months for patients treated with
interferon alone (P .03).22
Our study has limitations mainly associated with the
use of the SEER database. Several aspects critical to the
evaluation of survival are missing from the SEER database. Although one can assume the metastatic gastric cancer patients will be treated with systemic chemotherapy,
the SEER database lacks this important piece of information. In addition, there is missing surgical data on resection margin status, extent of lymphadenectomy or
information if resection was complete. From a radiation
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point of view, there is no available information if concurrent chemotherapy was used with radiation, the radiation
field design and technique, or dose of radiation used.
There is also missing information on patients nutritional
status and performance status. Although burden of disease
was not quantified, staging and location of the primary tumor, lymph nodes, and metastases was provided and
accounted for in the MVA. Finally, it is impossible to fully
understand from SEER why some people may have
received surgery and/or radiation therapy as part of their
treatment management. It is possible that healthier
patients, hence better prognosis patients, received these
locoregional treatments. However, despite these inherent
biases, SEER documents the real world outcomes of these
patients. Although these limitations may confound the
results, our findings do elucidate a possible association
between surgery and radiation therapy and improved survival for metastatic gastric cancer patients.
Conclusions

Surgical resection and radiation therapy are associated

with increased overall survival in metastatic gastric cancer
patients from the SEER database. Caution must be exercised before locoregional treatments are recommended in
the management of metastatic gastric cancer, because
there are no randomized data to validate this finding and
that there is significant data that are missing from the
SEER to properly stratify patients. However, it does warrant the need for prospective clinical trials addressing the
role of locoregional treatment in well-defined patient
cohorts with metastatic gastric cancer.
FUNDING SOURCES
No specific funding was disclosed.

CONFLICT OF INTEREST DISCLOSURE

The authors made no disclosure.

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