INTRODUCTION —
Gastric cancer is one of the most common cancers worldwide [1]. However, there are significant differences in the incidence of gastric cancer by region [2]. The value of screening asymptomatic individuals for gastric cancer is controversial even in areas with a relatively high incidence of gastric cancer [3]. This topic will review the screening of gastric cancer. The epidemiology, risk factors, pathology, pathogenesis, clinical features, diagnosis, and management of gastric cancer are discussed in detail separately. (See "Epidemiology of gastric cancer" and "Risk factors for gastric cancer" and "Clinical presentation, diagnosis, and staging of gastric cancer" and "Early gastric cancer: Clinical features, diagnosis, and staging" and "Early gastric cancer: Management and prognosis" and "Surgical management of invasive gastric cancer" and "Adjuvant and neoadjuvant treatment of gastric cancer" and "Gastric cancer: Pathology and molecular pathogenesis".)
SCREENING MODALITIES —
The two main modalities for gastric cancer screening are upper endoscopy and contrast radiography.
Upper endoscopy — Upper endoscopy allows for direct visualization of the gastric mucosa and for biopsies to be obtained for diagnosing precancerous lesions such as gastric atrophy, intestinal metaplasia, or gastric dysplasia in addition to gastric cancer. Although it is more invasive and has a higher cost, upper endoscopy is also more sensitive for diagnosing a variety of gastric lesions than alternative diagnostic strategies. (See 'Test performance' below.)
Contrast radiography — Double-contrast barium radiographs with photofluorography or digital radiography can identify malignant gastric ulcers, infiltrating lesions, and some early gastric cancers. Contrast radiography is less invasive but less sensitive than upper endoscopy. (See 'Test performance' below.)
Other tests — While other modalities of screening for gastric cancer or its precursors have been proposed, further studies are needed to support their use.
●Serum pepsinogen – A low serum pepsinogen I concentration and a low serum pepsinogen I/II ratio are suggestive of the presence of atrophic gastritis, a risk factor for gastric cancer. Serum pepsinogen testing has therefore been proposed to identify higher-risk individuals who could benefit from gastric cancer screening with upper endoscopy [4-9]. However, in a pooled meta-analysis of 27 population-based screening studies and 15 studies in selected high-risk groups (eg, atrophic gastritis) that included approximately 300,000 individuals, the pooled sensitivity and specificity of serum pepsinogen (pepsinogen I level ≤70 ng/mL and serum pepsinogen I/II ratio <3) for gastric cancer were only 77 and 73 percent in population-based studies and 57 and 80 percent in selected high-risk groups [4].
●Serum trefoil factor 3 – Serum trefoil factor 3 (TFF3) is a small, stable protein expressed in the goblet cells of the small and large intestine and in gastric intestinal metaplasia. In one study, the sensitivity and specificity of serum TFF3 for detection of gastric cancer were both 81 percent compared with 45 and 88 percent, respectively, for serum pepsinogen (pepsinogen I level ≤70 ng/mL and serum pepsinogen I/II ratio <3) [10]. The combination of pepsinogen and TFF3 may provide even higher sensitivity for gastric cancer [11]. Prospective studies are needed to compare the performance of TFF3 with upper endoscopy and to establish its diagnostic utility.
●MicroRNAs – At least three microribonucleic acids (miRNAs), miRNA-421, miRNA 18a, and miR-106a, are highly expressed in gastric cancers and are detectable in peripheral blood and gastric aspirates [12-14]. Assays for multiple miRNAs may further improve diagnostic accuracy [15]. However, additional studies are needed to define the role of these miRNAs as biomarkers for gastric cancer.
●Multianalyte blood tests – An early study examining combinations of tumor-specific circulating proteins and mutations in cell-free deoxyribonucleic acid (DNA) in the blood (CancerSEEK) suggests promise for early detection of potentially resectable gastric cancer (sensitivity 75 percent with a high degree of specificity) [16]. However, further data are needed to establish clinical utility and demonstrate that early diagnosis of gastric cancer using this assay saves lives.
BENEFITS AND HARMS OF SCREENING —
Several key factors inform decisions about screening. These include characteristics of available screening tests (ie, are they accurate, acceptable, feasible, safe, and cost-effective), the disease (ie, is it common and/or deadly), its treatment (ie, does early treatment improve outcomes) and, most importantly, whether the net benefits of screening and treatment outweigh potential harms. These components are summarized below and described more generally separately. (See "Evidence-based approach to prevention".)
Test performance — Although upper endoscopy and contrast radiography have not been directly compared, studies suggest that both modalities have similar specificity, but endoscopic screening is more sensitive for gastric cancer screening [17-21]. In a population-based study in Republic of Korea that included 2,690,731 individuals who underwent gastric cancer screening, gastric cancer detection rates were comparable with upper endoscopy and upper gastrointestinal (GI) series (2.61 and 0.68 per 1000 screenings, respectively) [22]. Both studies had a specificity of 96 percent for detecting gastric cancer. However, the sensitivities of upper endoscopy versus upper GI series were 69 and 37 percent, respectively. The sensitivity of upper endoscopy in detecting a localized gastric cancer was also significantly higher as compared with upper GI series (68 versus 32 percent). There was no difference in interval cancer rates (1.2 per 1000 screenings for both groups).
Other data suggest that for detecting early gastric cancer, the sensitivity of a barium study may be as low as 14 percent [23]. However, a barium study may be superior to upper endoscopy in patients with linitis plastica. The decreased distensibility of the stiff, "leather-flask" appearing stomach is more obvious on the radiographic study, and the endoscopic appearance may be relatively normal. (See "Early gastric cancer: Clinical features, diagnosis, and staging" and "Clinical presentation, diagnosis, and staging of gastric cancer".)
Potential benefits
●Cancer mortality – Randomized trials have not evaluated whether gastric cancer screening reduces mortality from gastric cancer either in high- or low-incidence populations. Evidence supporting the efficacy of screening comes from case-control and cohort studies [17,24-28] and epidemiologic data that correlate the onset of population-based screening programs with declining rates of death from gastric cancer [29]. In a meta-analysis of 10 observational studies that included 342,013 participants in Asia, endoscopic screening was associated with a reduced risk of gastric cancer mortality (relative risk [RR] 0.60; 95% CI 0.49-0.73) [30].
●Cancer detection – The impact of screening on rates of detecting gastric cancer is unclear. The above-mentioned meta-analysis did not find an association between endoscopic screening and the incidence of gastric cancer (RR 1.14; 95% CI 0.93-1.40), although these results were imprecise, and the analysis included only two studies [30,31].
Potential harms — The potential harms of screening include those that result from screening itself and the risks of downstream testing and treatment. (See "Evidence-based approach to prevention", section on 'Unintended consequences of screening'.)
●False-positive results – Although upper endoscopy yields higher test accuracy for gastric cancer screening than other screening modalities, studies suggest a significant risk of false-positive results. In a study of endoscopic screening in Japan, false-positive rates with endoscopic screening were 15 percent in the first round of screening (prevalence screening) and 11 percent in a subsequent round of screening (incidence screening) [32].
●False-negative results – False-negative results may provide a false sense of reassurance or potentially deter patients from adopting behaviors that modify their risk of developing gastric cancer (eg, quitting smoking or treating Helicobacter pylori [H. pylori] infection). False-negative rates with gastric cancer screening are lower with endoscopic than radiographic screening. In one study, false-negative rates ranged from 2.3 to 4.5 percent with upper endoscopy and 10.7 to 11.5 percent with contrast radiography [32]. Other data suggests that false-negative barium studies can occur in as many as 50 percent of cases [33].
●Complications – Complication rates with both radiographic and endoscopic screening procedures are relatively low (<1 percent) [34]. The most common adverse effects of upper endoscopy include bleeding, perforation, infection, and adverse cardiopulmonary events. Intestinal obstruction has been reported as an uncommon complication of screening with contrast radiography [34]. (See "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Adverse events'.)
●Overdiagnosis – Overdiagnosis is defined as the detection of cancers by screening that would have remained undetected without screening and would not result in significant adverse clinical outcomes (see "Evidence-based approach to prevention", section on 'Risk of overdiagnosis (pseudodisease) in cancer screening'). Studies suggest that some degree of overdiagnosis occurs with gastric cancer screening, although precise estimates of its magnitude vary [34,35].
Cost-effectiveness — Screening for gastric cancer may be cost-effective for high-risk subgroups but not low-risk populations [36,37]. A cost-effectiveness analysis found that in a high-risk group of Chinese males ages 50 to 70 years (standardized incidence of gastric cancer of 25.9 per 100,000 population), screening with upper endoscopy every two years was highly cost-effective (USD $28,836 per quality-adjusted life-years saved [36]). By contrast, averting one gastric cancer death in males in the United States, assuming an incidence of gastric cancer of <10 per 100,000 population, would cost approximately USD $247,600, which does not compare favorably with other generally accepted cancer screening interventions. (See "A short primer on cost-effectiveness analysis".)
SCREENING STRATEGIES —
Screening for gastric cancer is controversial, and strategies for screening differ based on the incidence of gastric cancer.
Universal screening in regions with high incidence of gastric cancer
●Screening strategies – Some countries with a high incidence of gastric cancer (eg, Japan, Republic of Korea, Venezuela, and Chile) have implemented universal or population-based screening for gastric cancer [17-19]. However, there are no data from randomized trials that demonstrate a mortality benefit with universal gastric cancer screening or evaluate the relative balance between its potential benefits and risks, such as overdiagnosis, downstream testing, and complications. (See 'Potential benefits' above.)
Screening modality and intervals vary by country. As examples:
•In Japan, guidelines recommend initiating gastric cancer screening in individuals age 50 years or older [34]. The primary screening method is upper endoscopy every two to three years due to its high sensitivity and efficacy to detect early-stage gastric cancer. Barium-based imaging studies every one to two years are still an accepted screening method, but data suggest it is less effective in detecting gastric cancer than endoscopy [34,38].
•In Republic of Korea, guidelines recommend gastric cancer screening with upper endoscopy every two years for individuals between ages 40 and 75 years [39-41].
●Optimal frequency – The optimal interval for screening has not been established in randomized trials. A two-year screening interval is supported by at least one study that evaluated the mean sojourn time (MST) for gastric cancer (ie, the asymptomatic period during which a cancer can be detected through screening tests before typical symptoms develop) in a cohort of 61,000 Korean males voluntarily attending a cancer screening program and rescreened by endoscopy [42]. A total of 91 incident cases were found during 19,598,598 person-years of follow-up, and the MST for gastric cancer was 2.4 years (95% CI 1.9-3). Of note, the MST was shorter in individuals 40 to 49 years of age (1.3 years, 95% CI 1-1.7) than the MST in those 50 to 59 years of age or 60 to 69 (3.2 and 3.7, respectively).
At least some data suggest that the screening interval may be widened to a three-year rather than a two-year interval without significantly decreasing the proportion of gastric neoplasms that can be adequately treated by endoscopic methods [43-45]. However, intervals longer than three years may be associated with a greater risk of more advanced-stage cancer at diagnosis. As an example, in a retrospective cohort study of 2485 patients with gastric adenocarcinoma in Republic of Korea, as compared with individuals who underwent annual screening for gastric cancer, the risk of advanced cancer was higher in individuals who underwent screening at four- or five-year intervals (four-year interval odds ratio [OR] 2.5, 95% CI 1.4-4.5, five-year interval OR 2.2, 95% CI 1.3-3.7) but not in individuals who underwent screening at two- or three-year intervals [43]. In subgroup analysis, individuals with a family history of gastric cancer and individuals in their 60s were more likely to be diagnosed with a higher stage of gastric cancer if upper endoscopies were performed every three years as compared with annually (family history of gastric cancer OR 2.68, 95% CI 1.3-5.7, gastric cancer in 60s OR 2.09, 95% CI 1-4.3).
Selective screening of high-risk subgroups in regions with low incidence of gastric cancer
Approach and rationale for screening
●Individuals at elevated risk – In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy is reserved for specific subgroups at high risk for gastric cancer [46-57].
We suggest screening for gastric cancer with upper endoscopy in the following subgroups of individuals at elevated risk for gastric cancer:
•First-generation immigrants from regions with a moderate to high incidence of gastric cancer
•Individuals with a family history of gastric cancer in a first-degree relative without a known hereditary cancer syndrome
Specific screening recommendations for other groups with an increased risk of gastric cancer, including those with hereditary cancer syndromes, are discussed separately. (See 'Hereditary syndromes' below and 'Other conditions' below.)
●Rationale for screening – Because the effectiveness of gastric cancer screening in reducing cancer-related mortality is uncertain, we discuss the potential benefits and harms of screening and individualize screening decisions for each patient. This includes an appraisal of the patient's risk of gastric cancer, including the presence of additional risk factors for gastric cancer, such as a history of regular tobacco use, non-white race and ethnicity, country of origin, age, diet, infection with Helicobacter pylori (H. pylori), and socioeconomic status. Additionally, screening should only be offered to those who would be candidates for treatment if a lesion is detected. (See 'Benefits and harms of screening' above and "Risk factors for gastric cancer".)
The rationale for screening in these patients is based on indirect evidence from observational studies of screening programs in high-prevalence countries and expert consensus [58] (see 'Universal screening in regions with high incidence of gastric cancer' above). There is no direct evidence that supports a mortality benefit for gastric cancer screening in these subgroups.
●Frequency and duration – The optimal frequency and duration of gastric cancer screening are not established in these subgroups. Recommended screening frequency and duration vary by diagnosis and are based on expert consensus. These are discussed below. (See 'First-generation immigrants from regions with a moderate to high incidence of gastric cancer' below and 'Family history of gastric cancer in a first-degree relative without known hereditary cancer syndrome' below and 'Hereditary syndromes' below and 'Other conditions' below.)
First-generation immigrants from regions with a moderate to high incidence of gastric cancer — For individuals who are first-generation immigrants from regions with moderate to high incidence of gastric cancer, we perform an upper endoscopy every two to three years.
We initiate gastric cancer screening at age 45 and continue until age 75 as long as the individual is in good health and both willing and able to undergo cancer screening and treatment. In the United States, starting screening at age 45 coincides with the age for colorectal cancer (CRC) screening in average-risk individuals, so that the upper endoscopy can occur at the same time as screening colonoscopy if that modality is used for CRC screening (see "Screening for colorectal cancer: Strategies in patients at average risk"). Alternatively, clinicians may follow the gastric cancer screening guidelines used in regions with a high incidence of gastric cancer [58]. (See 'Universal screening in regions with high incidence of gastric cancer' above and "Epidemiology of gastric cancer", section on 'Global incidence'.)
Family history of gastric cancer in a first-degree relative without known hereditary cancer syndrome — For patients with gastric cancer in a first-degree relative and no known hereditary gastrointestinal (GI) polyposis syndrome or hereditary cancer syndrome, we initiate screening for gastric cancer with upper endoscopy 10 years earlier than the age of the youngest affected relative [58]. We perform an upper endoscopy every two to three years until age 75 or as long as the individual is in good health and is both willing and able to undergo cancer screening.
Gastric cancer screening for those with known hereditary GI polyposis syndromes or hereditary cancer syndromes is discussed separately. (See 'Hereditary syndromes' below.)
Hereditary syndromes
Hereditary GI polyposis syndromes — For patients with hereditary gastrointestinal (GI) polyposis syndromes, gastric cancer screening guidelines are discussed in the relevant UpToDate topics.
•Familial adenomatous polyposis (FAP) – (See "Familial adenomatous polyposis: Screening and management of patients and families", section on 'Upper gastrointestinal tumors'.)
•GAPPS – Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), a hereditary syndrome that predisposes patients to gastric cancer), is also a genetic variant of FAP. Although data are limited, patients with GAPPS follow the same gastric cancer screening guidelines as those with FAP. (See "Risk factors for gastric cancer", section on 'Familial intestinal gastric cancer'.)
•Peutz-Jeghers syndrome – (See "Peutz-Jeghers syndrome: Clinical manifestations, diagnosis, and management", section on 'Cancer screening'.)
•Juvenile polyposis syndrome – (See "Juvenile polyposis syndrome", section on 'Upper gastrointestinal tract cancer'.)
•MUTYH-associated polyposis – (See "MUTYH-associated polyposis", section on 'Extracolonic surveillance'.)
Hereditary cancer syndromes — For patients with certain hereditary cancer syndromes that are associated with the development of gastric cancer, gastric cancer screening guidelines are discussed in the relevant UpToDate topics.
•Familial intestinal gastric cancer – (See "Risk factors for gastric cancer", section on 'Familial intestinal gastric cancer'.)
•Lynch syndrome – (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Cancer screening and management", section on 'Gastric cancer'.)
•Li-Fraumeni syndrome – (See "Li-Fraumeni syndrome", section on 'Cancer surveillance strategy'.)
•Diffuse gastric and lobular breast cancer syndrome (DGLBCS) – High-risk individuals from families with DGLBCS, previously known as hereditary diffuse gastric cancer, are not good candidates for gastric cancer screening because of the propensity of these tumors to arise beneath an intact mucosa and elude radiographic and endoscopic detection. Instead, such patients are typically treated with prophylactic gastrectomy. (See "Diffuse gastric and lobular breast cancer syndrome" and "Surgical management of gastric cancer in patients with DGLBCS".)
Other conditions
●Gastric adenomas – For patients with gastric adenoma, gastric cancer screening guidelines are discussed separately. (See "Gastric polyps", section on 'Management'.)
●Pernicious anemia – For patients with pernicious anemia, gastric cancer screening guidelines are discussed separately. (See "Treatment of vitamin B12 and folate deficiencies", section on 'Additional considerations for pernicious anemia'.)
●Gastric intestinal metaplasia – For patients with gastric intestinal metaplasia, gastric cancer screening guidelines are discussed separately. (See "Gastric intestinal metaplasia", section on 'Endoscopic surveillance in selected patients'.)
What is the role of gastric cancer screening in patients with Helicobacter pylori infection? — We do not offer gastric cancer screening to patients with active or prior infection with H. pylori. By contrast, other experts perform gastric cancer screening with upper endoscopy for the high-risk subset of individuals with chronic H. pylori infection and at least one of the following [58]:
●History of regularly smoking tobacco (>20 pack-year history)
●Chronic consumption of high-salt diet, red meat, and processed meats and foods
●Individuals living under persistent poverty
Screening should only occur in patients who are appropriate candidates for the treatment of gastric cancer, if diagnosed, and after discussing the risks and benefits of gastric cancer screening, including the uncertainty regarding its mortality benefit.
Randomized trials have not evaluated whether screening for gastric cancer in those with H. pylori infection reduces gastric cancer mortality. These data are lacking for both the general population of individuals with H. pylori infection as well as those with H. pylori infection who are at elevated risk for gastric cancer due to other social or demographic factors.
Eradication of H. pylori is already encouraged in all individuals who are diagnosed with active H. pylori infection, and successful eradication of the bacteria reduces the risk of developing gastric cancer (see 'Helicobacter pylori eradication' below). Consequently, it is unclear whether gastric cancer screening affords additional benefit in those who have undergone H. pylori eradication.
Gastric cancer screening of all individuals with H. pylori infection would also involve upper endoscopies for a significant fraction of the population because H. pylori infection is common. In the United States, the overall prevalence of H. pylori infection ranges from 25 to 37 percent [59,60]. Seroprevalence is substantially higher among non-Hispanic Black Americans, Asian Americans, and Hispanic Americans [60,61].
PREVENTION
Helicobacter pylori eradication
●Reduced gastric cancer mortality – In randomized trials conducted in countries with a high incidence of gastric cancer, Helicobacter pylori (H. pylori) eradication reduces the risk of death from gastric cancer. In a meta-analysis of four randomized trials that included 6301 participants, H. pylori eradication reduced gastric cancer mortality (relative risk [RR] 0.61; 95% CI 0.40-0.92) [62].
●Reduced incidence of gastric cancer – In individuals with active H. pylori infection, successful eradication of H. pylori reduces the risk of subsequent gastric cancer. The benefit of H. pylori eradication on gastric cancer risk is generally not apparent until at least six to eight years posttreatment [63-65].
•Regions with high incidence of gastric cancer – In asymptomatic, healthy individuals living in regions with a high incidence of gastric cancer, routine eradication of H. pylori has been demonstrated to decrease rates of gastric cancer [66-71]. Representative studies include the following:
-In a meta-analysis of seven randomized trials that included 8323 healthy, asymptomatic individuals from countries in Asia, H. pylori eradication treatment reduced the risk of gastric cancer by approximately 55 percent compared with no eradication treatment (RR 0.54, 95% CI 0.40-0.72) [62].
-In areas of high gastric cancer incidence, successful eradication of H. pylori infection in those with first-degree relatives with gastric cancer has been demonstrated to reduce the risk of a subsequent gastric cancer. In a randomized trial in Republic of Korea, 1838 individuals with H. pylori infection and a first-degree relative with gastric cancer were randomly assigned to receive either H. pylori eradication therapy or placebo. At a median follow-up of 9.2 years, eradication therapy reduced the incidence of gastric cancer relative to placebo (1.2 versus 2.7 percent; hazard ratio [HR] 0.45) [63]. Further studies are necessary before this can be incorporated into routine clinical practice. (See "Risk factors for gastric cancer", section on 'Importance of Helicobacter pylori infection' and "Clinical presentation, diagnosis, and staging of gastric cancer", section on 'Issues related to helicobacter pylori infection'.)
Eradication of H. pylori infection in adults with precancerous lesions, such as gastric adenomas, has also been associated with lower rates of developing gastric cancer [69]. Similarly, eradication of H. pylori in those with diagnosed early gastric cancer is associated with a decreased severity of intestinal metaplasia, a precancerous condition with increased risk of developing gastric cancer [68].
•Regions with low incidence of gastric cancer – In asymptomatic, healthy individuals who live in regions with a low incidence of gastric cancer, data from observational studies indicate that eradication of H. pylori infection is associated with a lower incidence of gastric cancer [64,65]. However, the limitation of these studies is that a large percentage of the study population did not have posttreatment test-of-cure demonstrating successful H. pylori eradication. One study found a positive association only in the subset of participants with successful eradication of H. pylori [64].
●Limitations of H. pylori eradication in reducing gastric cancer incidence – Individuals with H. pylori infection and premalignant gastric mucosal changes may still progress to cancer despite H. pylori eradication. In a randomized trial conducted in China of 1630 asymptomatic individuals with H. pylori infection, the greatest benefit of H. pylori eradication treated with respect to gastric cancer risk reduction was among patients without gastric premalignant changes prior to treatment (HR 0.37, 95% CI 0.15-0.95) and also among those with posttreatment test-of-cure demonstrating successful H. pylori eradication (HR 0.46; 95% CI 0.26-0.83) [72].
In patients with early-stage gastric cancer, H. pylori eradication also reduces the risk of metachronous gastric cancer. Further details are discussed separately. (See "Early gastric cancer: Management and prognosis", section on 'Eradicate H. pylori infection'.)
Other indications for testing and eradication of H. pylori are discussed in detail separately. (See "Indications and diagnostic tests for Helicobacter pylori infection in adults" and "Treatment of Helicobacter pylori infection in adults".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gastric cancer".)
SUMMARY AND RECOMMENDATIONS
●General principles – Gastric cancer is one of the most common cancers worldwide. However, there are significant differences in the incidence of gastric cancer by geographic region. (See 'Introduction' above.)
●Screening modalities – The two main modalities for screening for gastric cancer are contrast radiography and upper endoscopy. Although upper endoscopy and contrast radiography have not been directly compared, studies suggest that both modalities offer comparable specificity, but endoscopic screening is the more sensitive for gastric cancer screening. While other modalities of screening for gastric cancer or its precursors have been proposed, there are limited data to support their use. (See 'Screening modalities' above and 'Test performance' above.)
●Uncertain efficacy of screening – Screening for gastric cancer is controversial even in areas with a relatively high incidence of gastric cancer. Although screening for gastric cancer may be cost-effective in high-risk subgroups, it is unclear whether screening improves clinical outcomes, such as mortality from gastric cancer. There are no data from randomized trials that evaluate the efficacy of gastric cancer screening in reducing gastric cancer incidence or deaths. Some observational studies suggest that the screening has contributed to detection of cancer in early stages and an overall decline in gastric cancer mortality. (See 'Potential benefits' above.)
●Risks of screening – The most important risks of gastric cancer screening include overdiagnosis and false-positive results with their accompanying risks of downstream testing and potential complications. Other risks associated with gastric cancer screening are false-negative results and, uncommonly, procedural complications of upper endoscopy or contrast radiography. (See 'Potential harms' above.)
●Screening strategies – Screening strategies differ based on the endemic incidence of gastric cancer. (See 'Screening strategies' above.)
•Universal screening in regions with a high incidence of gastric cancer – Universal or population-based screening for gastric cancer has been implemented in some countries with a high incidence of gastric cancer (eg, Japan, Republic of Korea, Venezuela, and Chile). Of note, there are no data from randomized controlled trials that demonstrate that gastric cancer screening reduces cancer-related mortality in these populations. (See 'Universal screening in regions with high incidence of gastric cancer' above.)
•Screening in high-risk subgroups in regions with a low incidence of gastric cancer – In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific subgroups at high risk of gastric cancer. In select subgroups of individuals at elevated risk of gastric cancer, we suggest screening with upper endoscopy, rather than no screening (Grade 2C). These subgroups are:
-First-generation immigrants from regions with a moderate to high incidence of gastric cancer
-Individuals with a family history of gastric cancer in a first-degree relative without a known hereditary cancer syndrome
The rationale for screening in these patients is based on indirect evidence from observational studies of screening programs in high-prevalence countries and expert consensus. Because the effectiveness of gastric cancer screening in reducing cancer-related mortality is uncertain, we discuss the potential benefits and harms of screening and individualize screening decisions for each patient. (See 'Selective screening of high-risk subgroups in regions with low incidence of gastric cancer' above.)
Screening recommendations for other individuals at increased risk for gastric cancer are discussed separately. These include those with hereditary gastrointestinal (GI) polyposis syndromes or hereditary cancer syndromes associated with the development of gastric cancer, gastric adenomas, pernicious anemia, or gastric intestinal metaplasia. (See 'Hereditary syndromes' above and 'Other conditions' above.)
•Role of gastric cancer screening in patients with H. pylori infection – We do not offer gastric cancer screening to patients with active or prior infection with Helicobacter pylori (H. pylori) because robust evidence is lacking to support the efficacy of screening this population. (See 'What is the role of gastric cancer screening in patients with Helicobacter pylori infection?' above.)
However, other experts perform gastric cancer screening with upper endoscopy for the high-risk subset of individuals with chronic H. pylori infection and at least one of the following:
-History of regularly smoking tobacco (>20 pack-year history)
-Chronic consumption of high-salt diet, red meat, and processed meats and foods
-Individuals living under persistent poverty
•Prevention of gastric cancer with H. pylori eradication – All individuals who have active infection with H. pylori should receive treatment because successful eradication of H. pylori reduces the gastric cancer incidence and death. (See 'Prevention' above and "Treatment of Helicobacter pylori infection in adults".)
ACKNOWLEDGMENT — We are saddened by the death of Mark Feldman, MD, who passed away in March 2024. UpToDate gratefully acknowledges Dr. Feldman's role as Section Editor on this topic and his dedicated and longstanding involvement with the UpToDate program.