Note: Separate PDQ summaries on Stomach (Gastric) Cancer Prevention, Gastric Cancer Treatment, and Levels of Evidence for Cancer Screening and Prevention Studies are also available.
Inadequate Evidence of Benefit Associated with Screening
Barium-meal gastric photofluorography and serum pepsinogen
Based on fair evidence, screening with barium-meal photofluorography or serum pepsinogen would not result in a decrease in mortality from gastric cancer in areas with relatively low incidence of the disease, such as the United States.[1,2,3,4]
Magnitude of Effect: Fair evidence for no reduction in mortality.
|Study Design: Evidence obtained from case-control and cohort studies, primarily from high-risk areas such as Eastern Asia.|
|Internal Validity: Fair.|
|Consistency: Poor in prospective studies.|
|External Validity: Poor. Studies on populations in high-risk areas may not be applicable to low-risk areas such as the United States.|
Magnitude of Effect: Inadequate evidence for mortality reduction.
|Study Design: Evidence from case-control and cohort studies from East Asia are generally consistent with a substantial reduction in gastric cancer mortality associated with endoscopic screening.|
|Internal Validity: Fair to poor. All of the studies are observational and subject to selection bias on the basis of the individual who chooses to be screened.|
|Consistency: Good among the observational studies.|
|External Validity: Poor—studies on populations in high-risk areas (East Asia) may not be applicable to low-risk areas such as the United States.|
Based on solid evidence, screening would result in uncommon but serious side effects associated with endoscopy, which may include perforation, cardiopulmonary events, aspiration pneumonia, and bleeding requiring hospitalization.
Magnitude of Effect: Solid evidence for rare but serious harms.
|Study Design: Evidence obtained from screening programs and from case series.|
|Internal Validity: Fair.|
|Consistency: Inadequate evidence.|
|External Validity: Poor.|
Incidence and Mortality
In 2021, it is estimated that 26,560 Americans will be diagnosed with gastric cancer and 11,180 will die of it. Two-thirds of people diagnosed with gastric cancer are older than 66 years. Gastric cancer is the fourth most common cancer in the world. The disease is much more common in other countries, principally Japan, Central Europe, Scandinavia, Hong Kong, South and Central America, the Soviet Union, China, and Korea. Gastric cancer is a major cause of death worldwide, especially in developing countries.
The major type of gastric cancer is adenocarcinoma (95%). The remaining malignant tumors include lymphomas, sarcomas, carcinoid tumors and other rare types. Distinguishing the common adenocarcinoma from the uncommon lymphoma may sometimes be difficult but is important, due to major differences in staging, treatment, and prognosis. Gastric adenocarcinomas can be further categorized into an intestinal type and a diffuse type. Intestinal-type lesions are frequently ulcerative and occur in the distal stomach more often than the diffuse type. Diffuse-type lesions are associated with a worse prognosis than the intestinal type. The intestinal type tends to be predominant in geographic regions with a high incidence of gastric carcinoma. The decline in the incidence of gastric cancer worldwide is largely due to a decrease in the number of intestinal-type lesions.
The incidence of gastric cancer in the United States has decreased fourfold since 1930 to approximately seven cases per 100,000 people. The reasons for this striking decrease in incidence are not fully understood but are suspected to be related to improved storage of food and changes in diet, such as decreased salt intake. Some populations of Americans are at elevated risk, including elderly patients with atrophic gastritis or pernicious anemia, patients with sporadic gastric adenomas, familial adenomatous polyposis, or hereditary nonpolyposis colon cancer, and immigrant ethnic populations from countries with high rates of gastric carcinoma.[10,11]
Risk factors for gastric cancer include the presence of precursor conditions such as chronic atrophic gastritis and intestinal metaplasia, pernicious anemia, and gastric adenomatous polyps. Genetic and environmental factors include a family history of gastric cancer; low consumption of fruits and vegetables; consumption of salted, smoked, or poorly preserved foods; and cigarette smoking.[12,13] There is consistent evidence that Helicobacter pylori infection of the stomach is strongly associated with both the initiation and promotion of carcinoma of the gastric body and antrum, and of gastric lymphoma.[14,15,16] The International Agency for Research on Cancer (IARC) classifies H. pylori infection as a cause of noncardia gastric carcinoma and low-grade B-cell mucosa-associated lymphatic tissue gastric lymphoma (i.e., a Group 1 human carcinogen).[17,18] Compared with the general population, people with duodenal ulcer disease may have a lower risk of gastric cancer.
Inadequate Evidence of Benefit Associated With Screening
Several screening techniques, including barium-meal photofluorography, gastric endoscopy, and serum pepsinogen have been proposed as screening methods for the early detection of gastric cancer. No randomized trials evaluating the impact of screening on mortality from gastric cancer have been reported.[13,20] Even in very high-risk areas, the positive predictive value (PPV) of the screening tests may be very low. In a screening program of 17,647 men aged 40 to 60 years in Wakayama City, Japan, the PPV of combined serum pepsinogen and barium meal with digital radiography over the 7-year period was 0.85%. The positive test rates were 19.5% for serum pepsinogen and 22.5% for radiography, with a cancer detection rate of 0.28%. Over the 7-year period, there was no reduction in gastric cancer mortality compared with an age-matched surrounding population.
Barium-meal gastric photofluorography
A national program of population-based screening for gastric cancer using barium-meal photofluorography has been ongoing since the 1960s in Japan. Participation rates have been in the range of only 10% to 20%.[13,21] Although there has been a coincident decrease in mortality from gastric cancer in Japan, mortality rates have been decreasing in many developed countries despite the lack of screening programs. Case-control studies from Japan show decreases in gastric mortality in people who have undergone screening, but results from prospective studies were not consistent.[13,20]
A pilot study of community-based photofluorography was conducted in Costa Rica using the same techniques as those used in Japan's national program (with consultation from Japanese experts). People were invited by letter from a population registry to attend two rounds of screening, and a total of 6,200 eligible screened participants (of a planned 12,000) were analyzed. Their gastric cancer mortality from 2 to 7 years after screening was compared with four control groups that had not been invited to be screened, and the relative risk was about 0.5 (no P value reported). The study was, however, prone to strong biases, including selection bias, and likely differential exclusion of people with previously diagnosed gastric cancer favoring the screened population. In addition, unlike the community controls, patients diagnosed with gastric cancer through the screening program were treated at a single referral center. The PPV of a suspicious fluorograph was 3%; the specificity in the two rounds was 67% and 80%; and the positivity rates were 34% and 20%. Despite the authors' belief that their results provided substantial evidence that routine screening would decrease gastric cancer mortality, they concluded that the costs of screening with photofluorography would be far too high in their country.
A screening study was begun in Venezuela in 1980, using radiographic fluorography. The efficacy of this program in reducing mortality from stomach cancer was evaluated by means of a case-control study, and there was no detectable reduction in mortality from gastric cancer.
Endoscopy appears to be more sensitive than photofluorography for the detection of gastric cancer.
A meta-analysis of gastric cancer endoscopic screening studies in Asia identified ten relevant studies, all nonrandomized. These studies were conducted during the period of 1989 to 2014 in South Korea, China, and Japan. Of the ten studies, a never-screened group was the comparator in six studies, a radiographic-screening group was the comparator in one study, and expected deaths based on population rates was the comparator in three studies. In some of the studies, the endoscopic screening was performed as part of a national screening program. The meta-analysis pooled risk ratio (RR) estimate of gastric cancer mortality associated with endoscopic screening was 0.60 (95% confidence interval [CI], 0.49–0.73), with all but one study showing an individual RR of 0.72 or lower. There was significant heterogeneity across studies (P = .001), which was because of the one study with an RR greater than one (1.01); removing that study resulted in no significant heterogeneity (P = .14). Pooled estimates for the four nested case-control studies and six cohort studies were 0.60 (95% CI, 0.47–0.76) and 0.57 (95% CI, 0.39–0.83), respectively. The pooled estimate for the six studies with the never-screened comparator group was 0.58 (95% CI, 0.48–0.70).
There are no studies evaluating the effect of screening with serum pepsinogen on gastric cancer mortality, and there are important limitations to its use as a screening test. Low serum pepsinogen levels indicate the presence of atrophic gastritis and are therefore applicable to the detection of presumed precursors for intestinal type gastric cancer rather than the diffuse type. In addition, there are no standard cut-off values of abnormality.[13,26] Finally, eradication of H. pylori and use of proton pump inhibitors for the management of indigestion change pepsinogen levels, making interpretation of results difficult in the setting of widespread use of these interventions.[13,21]
In Japan, measurement of serum pepsinogen levels I and II (PGI and PGII) in 5,113 subjects also screened by endoscopy (13 gastric cancers detected), used cut-off points for identifying risk for gastric cancer of less than 70 ng/mL for PGI and less than 3 ng/mL for the PGI:PGII ratio. This combination provided a sensitivity of 84.6%, a specificity of 73.5%, a PPV of 0.81%, and a negative predictive value of 99.6%.
Clinical considerations for high-risk groups
There may be justification for screening some populations of Americans at higher risk, although there is considerable discussion about how much incidence would make the examination worthwhile. Potential subgroups might include elderly patients with atrophic gastritis or pernicious anemia, patients with partial gastrectomy, patients with the diagnosis of sporadic adenomas, familial adenomatous polyposis, or hereditary nonpolyposis colon cancer, and immigrant ethnic populations from countries with high rates of gastric carcinoma.[10,11]
Evidence of Harm Associated With Screening
Harms of routine screening for gastric cancer are poorly quantitated or reported, and derive chiefly from screening experiences in very high-risk areas such as Japan. The most frequent harm is the occurrence of false-positive tests. Exposure to the low doses of radiation (about 0.6 mSv in photofluorography) carries a theoretical but poorly quantified risk of carcinogenesis. Additional rare complications of screening may include adverse effects of premedication (used for endoscopy and sometimes photofluorography), and bleeding or perforation from endoscopy. As with any screening test, there is a possibility of overdiagnosis with attendant overtreatment. Since harms such as perforation and bleeding may vary with the experience of the screening center, they may be higher in populations at low risk for gastric cancer, such as the United States, than in mass screening programs in Japan.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Description of the Evidence
Updated statistics with estimated new cases and deaths for 2021 (cited American Cancer Society as reference 1).
This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about stomach (gastric) cancer screening. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
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Levels of Evidence
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PDQ® Screening and Prevention Editorial Board. PDQ Stomach (Gastric) Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/stomach/hp/stomach-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389174]
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Last Revised: 2021-03-18
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