Ann Surg Oncol (2017) 24:3361–3367
DOI 10.1245/s10434-017-5992-2
ORIGINAL ARTICLE – GASTROINTESTINAL ONCOLOGY
Survival Rates for Patients with Resected Gastric
Adenocarcinoma Finally have Increased in the United States
Elliot G. Arsoniadis, MD1, Schelomo Marmor, PhD, MPH2, Gustave K. Diep, BS3, Jane Yuet Ching Hui, MD, MS2,
Eric H. Jensen, MD2, and Todd M. Tuttle, MD, MS2
1
Department of Surgery, University of Minnesota, Minneapolis, MN; 2Division of Surgical Oncology, Department of
Surgery, University of Minnesota, Minneapolis, MN; 3University of Minnesota Medical School, Minneapolis, MN
ABSTRACT
Background. In the United States, the overall survival
rates for gastric adenocarcinoma have remained low, with
surgical resection as the only therapy for many patients.
Given the advances in multimodality treatment and the
development of guidelines recommending adequate lymph
node evaluation, the authors determined whether overall
survival rates for patients with gastric adenocarcinoma
have increased in the United States.
Methods. The study used the Surveillance Epidemiology
and End Results (SEER) database to examine overall sur-
vival for patients with the diagnosis of gastric
adenocarcinoma between 1988 and 2013. The study cohort
was divided into five periods: 1988–1992, 1993–1997,
1998–2002, 2003–2007, and 2008–2013. Kaplan–Meier
methods and Cox proportional hazards modeling were used
to determine the effect that year of diagnosis had on overall
survival.
Results. The diagnosis was determined for 13,470 patients
between 1988 and 2013. The use of radiation therapy and
the proportion of patients who had at least 15 lymph nodes
evaluated significantly increased during the study period.
Unadjusted Kaplan–Meier estimates demonstrated signifi-
cantly better survival rates for the patients with a diagnosis
of gastric cancer in the later periods (2003–2007 and
Electronic supplementary material The online version of this
article (doi:10.1245/s10434-017-5992-2) contains supplementary
material, which is available to authorized users.
Ó Society of Surgical Oncology 2017
First Received: 2 May 2017;
Published Online: 11 July 2017
T. M. Tuttle, MD, MS
e-mail: tuttl006@umn.edu
2008–2013) than for those in the three earlier periods. In
our Cox proportional hazards model, recent period was
associated with a significantly lower hazard of 5-year
mortality.
Conclusion. This analysis demonstrated for the first time
that gastric cancer survival rates have significantly
improved in the United States during the past 2 decades.
This observation likely reflects improved adherence to
cancer treatment guidelines, including adequate lymph
node evaluation and delivery of adjuvant treatment more
consistently.
Gastric cancer is one of the most common causes of
cancer-related deaths worldwide.1 Despite a decreasing
incidence of gastric cancer during the past century, more
than 25,000 patients received a diagnosis of gastric cancer,
and more than 10,000 patients were estimated to have died
of the disease in the United States in 2016.2 Previous
reports have shown little to no improvement in survival
over time with surgical resection alone as the mainstay of
treatment.3 However, several landmark trials from the
previous decade have established the role of perioperative
chemotherapy, chemoradiation, or both for gastric
adenocarcinoma.4–6
In 2001, the results of the Southwest Oncology Group
Intergroup 0116 Trial showed improved overall and
recurrence-free survival for patients treated with postop-
erative chemoradiotherapy compared with surgery alone.
A follow-up study more than a decade later showed con-
tinued improvement at 10 years.5,6 In 2006, the MRC
Adjuvant Gastric Infusion of Chemotherapy (MAGIC)
Trial was published, demonstrating improved overall and
recurrence-free survival for patients receiving periopera-
tive chemotherapy compared with surgery alone.4 Thus,
current recommendations include either perioperative
3362
chemotherapy or postoperative chemoradiation.7 In addi-
tion, more extensive D2 lymph node dissections, a
mainstay of surgical therapy in Asia,8 have currently
become more commonplace in Western countries. These
developments have altered the current management of
gastric adenocarcinoma in the United States. The Current
National Comprehensive Cancer Network (NCCN)
Guidelines for gastric cancer currently recommend a
minimum of 15 lymph nodes for pathologic evaluation and
D2 lymphadenectomy.7
Given these advances, our study aimed primarily to
determine whether survival rates for gastric adenocarci-
noma have improved during the past several decades in the
United States. As a secondary goal, this study aimed to
determine whether the patterns of gastric cancer treatment
in the United States have changed and, if so, whether the
changes have contributed to improvements in survival over
time.
METHODS
Data
We used the Surveillance Epidemiology and End
Results (SEER) database (SEER 9 Registries). The SEER
cancer registries provide population-based cancer surveil-
lance for 18 areas that represent approximately 28% of the
United States.2 The patient demographic and tumor char-
acteristics collected by SEER include age at diagnosis,
race, primary tumor site, tumor laterality, histology type,
tumor stage, tumor grade, diagnostic confirmation, type of
surgery, radiation, vital status, and cause of death.
Patients
We limited our study to patients older than 18 years
with a microscopic diagnosis of gastric adenocarcinoma
who had undergone surgical resection between 1988 and
2013. We excluded patients with non-adenocarcinoma
gastric cancer, those with evidence of distant disease, those
with multiple primary malignancies in a lifetime, and those
with a diagnosis determined while in a nursing home, by
autopsy, or on a death certificate. As part of our sensitivity
analysis, when patients with missing data were excluded,
our results persisted. Surgery codes and stepwise ascer-
tainment of our study cohort are listed in the Online
Appendix.
Statistical Analysis
Using the Cochrane–Armitage test for trend, we deter-
mined unadjusted node evaluation and use of radiation
E. G. Arsoniadis et al.
during the 26-year study period. We evaluated the associ-
ation between year of diagnosis and survival using Kaplan–
Meier methods and Cox proportional hazards modeling.
We divided our cohort into five periods between the years
1988 and 2013 (1988–1992, 1993–1997, 1998–2002,
2003–2007, 2008–2013). Overall survival was calculated
from the date of diagnosis.
All Cox models included patients’ age, race (white,
black, Asian, other), gender, tumor grade (1–4 or
unknown), SEER stage (localized, regional, unknown),
number of lymph nodes evaluated, node positivity, receipt
of radiation therapy, and geographic location. Radiation
therapy included external beam radiation and radiation not
otherwise specified.
In all models, we performed sensitivity analyses to
confirm that the survival benefits persisted over time. We
limited our analysis to the nine SEER registries that con-
tributed data across our entire 26-year study period. We
also restricted our analyses to patients who survived
4 months or longer after diagnosis and to patients who had
at least 15 nodes removed. Finally, we examined patients
with node-positive/SEER regional disease and node-nega-
tive/SEER localized disease separately. All statistical
analyses were completed using SAS software, version 9.3
(SAS Institute, Cary, NC, USA).
RESULTS
We identified 13,470 patients with gastric adenocarci-
noma diagnosed between the years 1988 and 2013
(Table 1). The majority of the patients were older than
60 years (74%), non-Hispanic whites (65%), and male
(63%). Regional disease was diagnosed for 64% of these
patients, and 55% were node-positive.
We found that the overall use of radiation therapy
increased significantly during our study period, from 14%
in 1988, to 41% in 2013 (Fig. 1). The proportion of patients
with at least 15 lymph nodes evaluated also significantly
increased during our study period, from 23% in 1988–1992
to 51% in 2008–2013 (Fig. 2).
Association Between Year of Diagnosis and Survival
Overall, unadjusted Kaplan–Meier estimates demon-
strated significantly better survival rates for the patients
whose gastric cancer was diagnosed in the later periods
(2003–2007 and 2008–2013) compared with the three
earlier periods (Fig. 3). The median survival rate for the
patients with a diagnosis in the earliest period (1988–1992)
was only 27 months. In contrast, the median survival rate
was 49 months for patients with a diagnosis in the
2008–2013 period. This trend persisted when we restricted
Gastric Cancer Survival has Increased 3363

TABLE 1 Characteristics of the gastric adenocarcinoma patients in our cohort to those patients who survived 4 months or
the 1988–2013 period (n = 13,470) longer (data not shown) and to the patients who had at least
All patients 15 lymph nodes evaluated (Supplemental Fig. 1).
When our cohort was restricted to node-positive/SEER
n %
regional disease only, we found a significant increase in
Period overall survival from 25 months in the earliest period
1988–1992 2648 20 (1988–1992) to 32 months in the latest period (2008–2013)
1993–1997 2515 18 (p B 0.0001; Supplemental Fig. 2). When our cohort was
1998–2002 2961 22 restricted to node-negative/SEER localized disease only,
2003–2007 2660 20 we found a smaller (but significant) increase in survival
2008–2013 2686 20 between the earliest and latest periods (44 vs 46 months;
Age (years) p B 0.01; Supplemental Fig. 3).
18–39 425 3 In our Cox proportional hazards model, recent period
40–59 3130 23 (2008–2013) was associated with a significantly lower
60–79 7510 56 hazard of 5-year mortality (Table 2). Other factors inde-
80? 2405 18 pendently associated with 5-year mortality were patient
Gender age, gender, race, tumor grade, lymph node evaluation,
Male 8439 63 SEER stage, and use of radiation therapy (p B 0.05).
Female 5031 37
Race
DISCUSSION
Non-Hispanic white 8699 65
Black 1684 12 This analysis of the SEER database demonstrates for the
Asian 2936 22 first time that gastric cancer survival rates have signifi-
Other or unknown 151 1 cantly improved in the United States during the past two
Tumor grade decades. Our results illustrate that recent year of treatment
1 or 2 4324 32 was an independent predictor of decreased mortality when
3 7883 58 control was used for patient and tumor characteristics.
4 307 3 Improved survival persisted when we restricted our cohort
Missing/unknown 956 7 to those patients who survived 4 months or longer and to
SEER stage the patients who had at least 15 lymph nodes evaluated.
Localized 4840 36 Improved survival persisted when we restricted our cohort
Regional 8630 64 to those patients with node-positive/SEER regional disease
Radiation therapy and to those with node-negative/SEER localized disease.
Yes 9814 73 The improvement in survival was more pronounced for the
No 3656 27 patients with node-positive disease.
Node-positive Our findings are in contrast to those of other studies that
No 6108 45 evaluated survival rates for gastric cancer over time. Das-
Yes 7362 55 sen et al.9 reported that the 5-year survival rates for gastric
Registry cancer did not improve during a 20-year study period
San Francisco-Oakland 2535 18 (1989–2008) in the Netherlands. Similarly, in an analysis
Connecticut 2264 17 using the SEER database, Erbinger et al.10 reported that the
Metropolitan Detroit 2272 17 survival rates for patients with stage 4 gastric cancer did
Hawaii 1566 12 not appreciably improve over time (1998–2009). In con-
Iowa 1010 8 trast, a smaller study limited to two Chinese institutions
New Mexico 735 5 found an increase in 5-year survival rates from 39 to 53%
Seattle (Puget Sound) 1636 12 between 1991 and 2010 in its cohort of gastric cancer
Utah 505 4 patients.11
Metropolitan Atlanta 947 7 The reasons for the observed improvements in survival
rates for gastric cancer over time in the United States are
SEER Surveillance epidemiology and end results
likely multifactorial. Importantly, the increased use of
3364 E. G. Arsoniadis et al.

FIG. 1 Percentage of gastric

adenocarcinoma patients
receiving radiation treatment
over time (1988–2013)

FIG. 2 Percentage of gastric

adenocarcinoma patients with
15? lymph nodes evaluated
over time (1988–2013)

1.0 14.5% of patients with gastric adenocarcinoma received

chemotherapy and that only 6.7% received combined
chemoradiation therapy.12
0.8
In 2001, results of the Southwest Oncology Group-
Directed Intergroup Study 0116 were published, which
demonstrated significant improvement in both disease-free
and overall survival rates for patients who underwent
Survival Probability

0.6 gastrectomy plus postoperative chemoradiation therapy

compared with those who underwent gastrectomy alone.6
A follow-up analysis of this trial demonstrated that the
0.4 improvements in survival rates among patients who
received chemoradiation remained statistically significant
during a median follow-up period of 10.3 years.5
In 2006, Cunningham et al.4 published the results of the
0.2
MAGIC Trial demonstrating that perioperative
1988–1992
1993–1997 chemotherapy (epirubicin, cisplatin, fluorouracil) was
1998–2002
2003–2007 associated with significant improvements in overall sur-
2008–2013
0.0 vival versus surgery alone for patients with
0 10 20 30 40 50 60
Months
gastroesophageal cancer. The timing of these two landmark
studies and the improvements in 5-year survival found in
FIG. 3 Kaplan–Meier curves for overall survival of gastric adeno- our data are notable. Despite more than a decade of stag-
carcinoma by year groupings nation in survival rates between the late 1980s and the early
2000s, we observed significant improvement in survival
perioperative chemotherapy and postoperative chemoradi- rates starting in 2008. Consistent with Intergroup 0116, we
ation therapy has had an impact on survival rates in the observed increased survival rates for those patients
United States. Earlier reports in the 1990s found no sig- receiving radiation therapy and surgery compared with
nificant survival advantage for patients receiving surgery alone. We also observed an overall increase in the
postoperative adjuvant therapy.3 As a result, very few receipt of radiation therapy over time, from 14% in 1988 to
patients received any adjuvant therapy. A National Cancer 41% in 2013. Although we are unable to determine
Data Base (NCDB) study reported that in 1992–1993, only chemotherapy use in SEER, it is reasonable to infer that
Gastric Cancer Survival has Increased 3365

TABLE 2 Cox proportional hazard models and 5-year mortality

HR 95% CI p valuea

Diagnosis year group

1988–1992 1.00 Referent
1993–1997 1.03 0.96–1.10 0.47
1998–2002 1.06 1.00–1.14 0.07
2003–2007 0.97 0.90–1.04 0.36
2008–2013 0.84 0.78–0.91 \0.0001
Age categories
18–39 1.00 Referent
40–59 1.1 0.9–1.3 0.3
60–79 1.35 1.18–1.56 \0.0001
80? 1.99 1.72–2.30 \0.0001
Gender
Male 1.00 Referent
Female 0.89 0.85–0.93 \0.0001
Race
Non-Hispanic white 1.00 Referent
Black 0.98 0.92–1.06 0.66
Asian 0.77 0.71–0.83 \0.0001
Other 1.13 0.91–1.40 0.27
Tumor grade
1 or 2 1.00 Referent
3 1.32 1.26–1.39 \0.0001
4 1.32 1.14–1.53 0.0002
Missing/unknown 1.16 1.05–1.28 0.003
No. of nodes evaluated
0 1.36 1.25–1.49 \0.0001
1–9 1.00 Referent
10–14 0.91 0.85–0.97 0.003
15? 0.82 0.77–0.87 \0.0001
Missing 1.23 1.11–1.35 \0.0001
SEER stage
Localized 1.00 Referent
Regional 3.04 2.88–3.22 \.0001
Radiation
No radiation–surgery only 1.00 Referent
Radiation and surgery 0.80 0.76–0.84 \.0001
Adjusted for diagnosis year, age, gender, race, tumor grade, number of lymph nodes evaluated, SEER stage, radiation receipt, and registry
geographic location
HR Hazard ratio, CI confidence interval, SEER Surveillance epidemiology and end results
a
Significant at p \ 0.05 level

many patients receiving radiation therapy did so as a part of
a multimodal therapy plan that also included
chemotherapy.
More extensive lymphadenectomy and improved nodal
staging also may have contributed to the increased gastric
cancer survival rates observed in our study. During the
15-year follow-up period in the Dutch D1/D2 randomized
trial, D2 lymphadenectomy was associated with signifi-
cantly lower disease-specific mortality rates.13
In 1997, the American Joint Committee on Cancer
(AJCC) and the Union Internationale Contre le Cancer
(UICC) jointly published new guidelines on the nodal
staging of gastric cancer, recommending that at least 15
lymph nodes be assessed for accurate staging.14 Studies
3366
examining the effect of lymph node evaluation on survival
have shown improvement in survival with increased nodal
count. In an analysis of 3814 patients from the SEER
database, Smith et al.15 reported that the overall survival
rate was significantly improved with increased nodal
assessment and that the survival rate increased 7.6% for
every 10 lymph nodes assessed. In our study, we found that
lymph node evaluation significantly increased over time
and that evaluation of 15 or more lymph nodes was asso-
ciated with significantly decreased mortality rates.
However, even when we restricted our cohort to those
patients who had 15 or more lymph nodes evaluated, the
survival rates still were significantly improved in the later
periods.
Another potential explanation for the finding of
improved survival rates over time is decreased mortality
rates after gastric resection in more recent years. In two
separate National Surgery Quality Improvement Program
(NSQIP)-based analyses, Papenfuss et al.16 (2005–2010)
and Bartlett et al.17 (2005–2011) reported that the 30-day
mortality rates after total gastrectomy were 5.4 and 4.7%,
respectively., In a single-center study of 413 patients
undergoing total gastrectomy between 1988 and 2011, da
Costa et al.18 reported that 60-day mortality rates were
significantly reduced among later cohorts. The impact of
decreased postoperative mortality on our findings is prob-
ably minimal because we found that the gastric cancer
survival rates were improved in recent years even when we
excluded patients who died within the first 4 months after
diagnosis.
Improvements in radiographic staging in recent years
also may partially explain our findings. Incomplete staging
may lead to a higher proportion of non-curative gastrec-
tomies. Certainly, current imaging methods, including
computed tomography (CT), magnetic resonance imaging
(MRI), and fluorodeoxyglucose-positron emission tomog-
raphy (FDG-PET), have improved modern gastric cancer
staging compared with methods available in the late 1980s
and early 1990s. However, we found that the survival rates
were significantly better in 2008–2013 than in 2003–2007.
Also, given that the most common sites of metastatic dis-
ease are hepatic and peritoneal, it is unlikely that improved
radiographic imaging would detect metastases not found
with intraoperative exploration. Thus, the contribution of
improved staging to our findings of improved gastric can-
cer survival rates likely is small.
Our study had several important limitations. Most
importantly, the use of chemotherapy is not recorded in the
SEER database. Similarly, other important data such as
comorbidities, imaging, and margin status are not available
from SEER. Despite these limitations, this study is the first
to demonstrate that survival rates after gastrectomy for
E. G. Arsoniadis et al.
adenocarcinoma have significantly improved over time in
the United States.
CONCLUSION
Previous studies have reported few improvements in
survival rates for gastric cancer in the 1990s and early
2000s in the United States. In this analysis using the SEER
database, we found significant improvement in 5-year
survival rates between 1988 and 2013, with the most sig-
nificant improvements noted in the later two periods,
2003–2007 and 2008–2013. These results underscore the
importance of adopting the results of randomized trials into
clinical practice and the potential benefit of complying with
evidence-based guideline-recommended multidisciplinary
cancer care.
DISCLOSURES The authors have no financial disclosures.
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