Stomach Cancer: An Overview
- lukemarshall93
- 2 days ago
- 8 min read
Introduction / Background
Gastric (stomach) cancer ranks as the fifth most common cancer worldwide and the third leading cause of cancer-related mortality. The disease is characterised by late-stage diagnosis and poor overall survival, with five-year survival rates below 35% in most populations. Most gastric cancers are adenocarcinomas that develop following years of chronic inflammation and progressive premalignant changes. Early identification of high-risk individuals and intervention at premalignant stages offers the most promising pathway to reducing disease burden and mortality.
Key Facts:
Largely preventable disease: Most gastric cancers result from undiagnosed, lifelong H. pylori infection that can be identified and treated
Greatest risk factor: Chronic H. pylori infection, particularly CagA-positive strains, with infection typically acquired in childhood
Screening programs work: Countries with organised screening (Japan, Korea) have achieved 40-60% mortality reduction through early detection and intervention
Over 1 million new cases globally each year; survival varies dramatically by stage (<5% metastatic vs. 90% early-stage )
Growing absolute burden: While age-standardised rates are declining globally, absolute case numbers continue to increase due to population aging and growth
Rising healthcare costs: Treatment costs continue to increase; GI cancer spending projected to exceed $21 billion annually by 2030 in the US alone
Strong socioeconomic gradient: highest burden in populations lacking access to screening and treatment
Disease Pathology
Gastric cancer develops through the Correa pathway, progressing from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and invasive carcinoma over 20-30 years. This process is driven primarily by chronic Helicobacter pylori infection combined with environmental and genetic factors. Non-cardia (distal) cancers are strongly associated with H. pylori, while cardia (proximal) cancers share risk factors with oesophageal adenocarcinoma. Molecular classification has identified distinct genomic subtypes with implications for prognosis and targeted therapy.
Pathological Characteristics:
Intestinal-type cancers: well-differentiated, environmental risk factors; Diffuse-type: poorly differentiated, hereditary component, worse prognosis
CagA-positive H. pylori strains confer 6-12 fold increased cancer risk through chronic inflammation and epithelial damage
Epstein-Barr virus present in ~9% of cases, represents distinct molecular subtype
Hereditary diffuse gastric cancer (CDH1 mutations) accounts for 1-3% of cases
The Correa cascade represents the primary pathway for intestinal-type non-cardia cancer development
Prevalence
Global gastric cancer incidence shows striking geographic variation, with rates in Eastern Asia exceeding those in Western nations by 3-6 fold. In Australia, approximately 2,400 new cases and 1,100 deaths occur annually, representing relatively low incidence compared to global patterns. Remote and Indigenous Australian populations experience disproportionately higher rates of both H. pylori infection and gastric cancer, with incidence 2-3 times higher than non-Indigenous Australians. Migration studies demonstrate that risk patterns reflect early-life environmental exposures, particularly H. pylori acquisition.
Prevalence Data:
Highest incidence: Eastern Asia, Central/Eastern Europe, Latin America; Lowest: North America, Northern Europe, Australia/New Zealand
Australian Indigenous populations show 2-3 fold higher gastric cancer incidence, with H. pylori prevalence 60-80% in remote communities vs. 20-40% nationally
Male-to-female ratio approximately 2:1 globally
H. pylori infection prevalence strongly correlates with gastric cancer rates across populations
Median age at diagnosis 68-72 years, with incidence increasing sharply after age 50
Detection
Early detection significantly improves outcomes, but the asymptomatic nature of early disease presents a major challenge. Upper gastrointestinal endoscopy with systematic biopsy remains the gold standard, enabling visualisation and histological assessment of premalignant lesions. Risk stratification focuses on identifying high-risk individuals through H. pylori testing (particularly CagA-positive strains), detection of atrophic gastritis (serum pepsinogen I/II ratio), and endoscopic surveillance. Novel biomarker-based screening approaches, including blood-based tests for CagA-positive H. pylori, offer potential for population-level risk assessment without invasive procedures.
Detection Strategies:
Endoscopic screening in high-incidence countries (Japan, Korea) demonstrates 40-60% mortality reduction
Serum pepsinogen testing identifies atrophic gastritis with 70-80% sensitivity for non-invasive risk stratification
CagA antibody testing specifically identifies high-risk H. pylori infections (6-12 fold increased cancer risk)
Standard H. pylori serology detects infection but cannot distinguish virulent strains
Symptom-based detection results in late-stage diagnosis in >70% of non-screening populations
Surveillance intervals: annual for high-grade dysplasia, 3-yearly for extensive intestinal metaplasia, 5-yearly for atrophic gastritis
Treatment / Interventions
Management requires multidisciplinary approaches tailored to disease stage, with curative intent possible only through surgical resection. Early-stage tumours may be amenable to endoscopic resection with five-year survival exceeding 95%. Advanced disease requires gastrectomy with lymphadenectomy, often combined with perioperative chemotherapy. For H. pylori-positive individuals without cancer, eradication therapy eliminates the primary carcinogenic driver and reduces cancer risk by 30-50%, with greatest benefit before development of atrophic gastritis. Targeted therapies and immune checkpoint inhibitors have expanded treatment options for advanced disease, though median survival remains below 18 months for metastatic cases.
Intervention Approaches:
Surgical resection: five-year survival 60-70% for stage I-II vs. <10% for stage IV
H. pylori eradication reduces cancer risk by 33-47%, with number needed to treat of 15-40 to prevent one cancer over 10 years
Risk reduction >50% when eradication occurs before atrophic gastritis vs. 30% with established atrophy
Standard eradication regimens achieve 85-95% cure rates; successful treatment returns cancer risk to baseline within 5 years
Endoscopic surveillance prevents progression to invasive cancer in >90% of high-grade dysplasia cases
Population-based screening and eradication programs demonstrate cost-effectiveness with 10-15 year payback periods
Challenges
The primary challenge lies in late-stage presentation of symptomatic disease when curative treatment options are limited. Population-wide endoscopic screening remains prohibitively expensive in most countries, necessitating risk-stratification approaches. The global H. pylori prevalence (approximately 4.4 billion people) vastly exceeds cancer incidence, requiring methods to identify high-risk subsets rather than treating all infections. Increasing antibiotic resistance threatens eradication success rates. Health disparities contribute significantly to disease burden, with remote, Indigenous, and socioeconomically disadvantaged populations experiencing higher infection rates and reduced screening access.
Key Challenges:
70% of cases diagnosed at advanced stages in non-screening populations due to absent early symptoms
Universal endoscopic screening cost-effective only in populations with very high incidence
Limited access to validated, affordable biomarker-based risk stratification tools
Antibiotic resistance (particularly clarithromycin) reduces first-line therapy efficacy from >90% to <80% in many regions
Low awareness among public and healthcare providers regarding CagA-specific cancer risk
Remote and Indigenous communities face multiple barriers: higher infection prevalence, limited specialist access, lower screening participation
Surveillance fatigue reduces effectiveness of endoscopic monitoring programs
Opportunities
Blood-based screening for CagA-positive H. pylori represents a transformative opportunity for cost-effective population-level risk stratification. Integration of such testing into routine blood panels could identify the highest-risk 15-20% of infected individuals for eradication therapy and surveillance, avoiding unnecessary treatment of low-risk infections. Economic modelling demonstrates that comprehensive screening programs achieve cost-neutrality within 10 years through reduced cancer treatment costs, with accelerated benefits in high-prevalence populations. Targeted interventions for at-risk populations and integration with existing primary care infrastructure offer scalable pathways to reduce gastric cancer burden globally.
Key Opportunities:
CagA-specific screening: Low-cost blood test integrated into routine panels enables population-wide risk stratification without endoscopy
Impact of risk-stratified screening: Treats only high-risk 15-20% of infections, reduces overtreatment, achieves cost-neutrality in 10 years through prevention savings
Targeted population programs: Focus on high-prevalence groups (Indigenous, migrant communities from high-incidence regions) maximises cost-effectiveness and equity
Primary care integration: Incorporate testing into existing health checks, chronic disease management, and preventive care pathways
Screen-and-treat programs: Mass eradication campaigns in high-prevalence regions (e.g., Taiwan, Japan initiatives) demonstrate feasibility and population-level impact
Pediatric/young adult screening: Early-life intervention prevents establishment of premalignant changes, offering greatest cancer prevention benefit
Digital health platforms: Use of AI for endoscopic image analysis improves early lesion detection in surveillance programs
Test-and-treat at point-of-care: Rapid CagA testing enables immediate treatment initiation, improving adherence in remote areas
Public health campaigns: Raising awareness of H. pylori cancer risk and CagA status drives screening uptake and prevention behaviour
Links and References
Key Organisations and Resources
World Health Organization (WHO) - Cancer Fact Sheets
International Agency for Research on Cancer (IARC)
Cancer Australia - Gastric Cancer Statistics
Australian Institute of Health and Welfare (AIHW) - Cancer Data
https://www.canceraustralia.gov.au/cancer-types/stomach-cancer/stomach-cancer-statistics
American Cancer Society - Stomach Cancer Information
European Society for Medical Oncology (ESMO) Guidelines
Epidemiology and Global Burden
Sung H, Ferlay J, et al. "Global Cancer Statistics 2020: GLOBOCAN Estimates" CA: A Cancer Journal for Clinicians (2021)
https://doi.org/10.3322/caac.21660
Comprehensive global incidence and mortality data by country and region
Morgan E, et al. "The current and future incidence and mortality of gastric cancer in 185 countries, 2020–40" eClinicalMedicine (2022)
https://doi.org/10.1016/j.eclinm.2022.101404
Population-based modelling of gastric cancer projections through 2040
Thrift AP, El-Serag HB. "Burden of Gastric Cancer" Clinical Gastroenterology and Hepatology (2020)
https://doi.org/10.1016/j.cgh.2019.07.045
Review of geographic patterns and temporal trends in gastric cancer burden
Liu J, et al. "Global incidence and mortality trends of gastric cancer and predicted mortality by 2035" BMC Public Health (2024)
https://doi.org/10.1186/s12889-024-19104-6
Joinpoint analysis of historical trends with predictions to 2035
Arnold M, et al. "Is gastric cancer becoming a rare disease?" Gut (2020)
https://doi.org/10.1136/gutjnl-2019-320234
Analysis of age-standardized rates versus absolute case numbers due to population aging
Pathology and Molecular Classification
Correa P. "Human gastric carcinogenesis: a multistep and multifactorial process" Cancer Research (1992)
https://pubmed.ncbi.nlm.nih.gov/1582252/
Seminal description of the histological cascade from gastritis to cancer
The Cancer Genome Atlas Research Network. "Comprehensive molecular characterization of gastric adenocarcinoma" Nature (2014)
https://doi.org/10.1038/nature13480
Molecular subtypes of gastric cancer with therapeutic implications
Lauren P. "The two histological main types of gastric carcinoma" Acta Pathologica et Microbiologica Scandinavica (1965)
https://doi.org/10.1111/j.1699-0463.1965.tb04704.x
Classic classification into intestinal and diffuse types
H. pylori and Prevention
Ford AC, Yuan Y, et al. "Helicobacter pylori eradication therapy to prevent gastric cancer" Gut (2020)
https://doi.org/10.1136/gutjnl-2020-320839
Meta-analysis demonstrating 33-47% cancer risk reduction through H. pylori eradication
Malfertheiner P, Megraud F, et al. "Management of Helicobacter pylori infection - Maastricht V/Florence Consensus" Gut (2017)
https://doi.org/10.1136/gutjnl-2016-312288
International consensus on H. pylori diagnosis, treatment, and indications
Liou JM, Malfertheiner P, Lee Y-C, et al. “Screening and eradication of Helicobacter pylori for gastric cancer prevention: Taipei Global Consensus II” Gut (2025)
https://doi.org/10.1136/gutjnl-2025-336027
Updated global consensus recommending H. pylori test-and-treat strategies for primary prevention of gastric cancer.
Peek RM, Blaser MJ. "Helicobacter pylori and gastrointestinal tract adenocarcinomas" Nature Reviews Cancer (2002)
https://doi.org/10.1038/nrc886
Mechanisms by which CagA-positive strains drive carcinogenesis
Clinical Guidelines and Management
Japanese Gastric Cancer Association. "Japanese gastric cancer treatment guidelines" Gastric Cancer (2021)
https://doi.org/10.1007/s10120-020-01042-y
Evidence-based guidelines from highest-incidence region with extensive screening experience
Pimentel-Nunes P, Libânio D, et al. "Management of epithelial precancerous conditions and lesions in the stomach (MAPS II)" Endoscopy (2019)
https://doi.org/10.1055/a-0859-1883
European guidelines for surveillance intervals and management of premalignant lesions
Ajani JA, et al. "Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology" Journal of the National Comprehensive Cancer Network (2022)
https://doi.org/10.6004/jnccn.2022.0008
US treatment guidelines covering diagnosis, staging, and multimodal therapy
Lordick F, Carneiro F, Cascinu S, et al. “Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up” Annals of Oncology (2022)
https://doi.org/10.1016/j.annonc.2022.07.004
Current European guideline replacing 2016 ESMO guidance; covers staging, peri-operative, systemic, and follow-up care.
Economic Burden and Cost Analysis
Stukalin I, Ahmed NS, Fundytus AM, et al. “Trends and Projections in National United States Health Care Spending for Gastrointestinal Malignancies (1996–2030)” Gastroenterology (2021)
https://doi.org/10.1053/j.gastro.2021.12.244
Analysis of US GI-cancer spending 1996–2016 with projections to 2030.
Desai A, et al. "Trends and Projections in National U.S. Healthcare Spending for Gastrointestinal Malignancies (1996–2030)" American Journal of Gastroenterology (2022)
https://doi.org/10.14309/ajg.0000000000001628
Comprehensive cost analysis projecting >$21 billion annually for GI cancers by 2030
Mariotto AB, et al. "Medical Care Costs Associated with Cancer Survivorship in the United States" Cancer Epidemiology, Biomarkers & Prevention (2020)
https://doi.org/10.1158/1055-9965.EPI-19-1534
National cost estimates including gastric cancer across phases of care
Solanki S, Chakinala RC, Haq KF, et al. “Inpatient burden of gastric cancer in the United States” Annals of Translational Medicine (2019)
https://atm.amegroups.org/article/view/32144/html
Nationwide Inpatient Sample (2001–2011) study quantifying hospitalization trends and costs for gastric cancer. (No DOI listed by journal page.)
Li Q, et al. "Expenditure and Financial Burden for Stomach Cancer in China" Frontiers in Public Health (2020)
https://doi.org/10.3389/fpubh.2020.00310
Demonstrates catastrophic financial burden with patients spending 64% of annual household income
Screening and Early Detection
Hamashima C, et al. "The Japanese guidelines for gastric cancer screening" Japanese Journal of Clinical Oncology (2018)
https://doi.org/10.1093/jjco/hyy053
Methods and outcomes of population-based endoscopic screening programs
Miki K. "Gastric cancer screening using the serum pepsinogen test method" Gastric Cancer (2006)
https://doi.org/10.1007/s10120-006-0397-0
Non-invasive biomarker approach for identifying atrophic gastritis
Choi IJ, et al. "Family History of Gastric Cancer and Helicobacter pylori Treatment" New England Journal of Medicine (2020)
https://doi.org/10.1056/NEJMoa1909666
Demonstrates benefit of H. pylori eradication in high-risk families
