Hidden in plain sight as a leading global killer, stomach cancer claimed over a million lives in 2020 alone, presenting a complex health challenge that varies dramatically by geography, genetics, and lifestyle.
Key Takeaways
- In 2020, stomach cancer was the fifth most common malignancy worldwide, with 1,089,103 new cases reported globally according to GLOBOCAN estimates
- The age-standardized incidence rate (ASIR) for stomach cancer in men worldwide was 18.0 per 100,000 in 2020, significantly higher than in women at 8.8 per 100,000
- Eastern Asia had the highest ASIR for stomach cancer at 32.5 per 100,000 in men in 2020, accounting for over 50% of global cases despite comprising only 22% of the world population
- Helicobacter pylori infection increases stomach cancer risk by 5.6-fold (95% CI 3.7-8.6) in meta-analysis of 12 studies
- Chronic H. pylori infection is classified as a Group 1 carcinogen by IARC, responsible for 89% of non-cardia stomach cancers
- Smoking doubles the risk of stomach cancer (RR 1.92, 95% CI 1.46-2.53) in never-smokers' adjusted meta-analysis
- Early satiety occurs in 60-80% of advanced stomach cancer patients at diagnosis
- Unintentional weight loss >10% body weight in 3 months seen in 60% of symptomatic cases
- Epigastric pain or discomfort reported by 50-70% of patients prior to diagnosis
- Neoadjuvant chemotherapy (FLOT regimen) improves R0 resection rate to 85% from 65% surgery alone in locally advanced
- Perioperative ECF (epirubicin, cisplatin, 5-FU) increases 5-year survival to 36% vs. 23% surgery alone (MAGIC trial)
- Trastuzumab added to chemotherapy doubles response rate to 47% in HER2+ advanced gastric cancer (ToGA trial)
- 5-year OS after curative resection: stage I 70-90%, stage II 40-60%, stage III 20-30%
- Localized stomach cancer 5-year relative survival 75% (US SEER 2013-2019)
- Regional spread survival drops to 36%, distant metastasis 7%
Stomach cancer remains a global health burden despite declining incidence rates in many countries.
Clinical Presentation
- Early satiety occurs in 60-80% of advanced stomach cancer patients at diagnosis
- Unintentional weight loss >10% body weight in 3 months seen in 60% of symptomatic cases
- Epigastric pain or discomfort reported by 50-70% of patients prior to diagnosis
- Iron deficiency anemia (microcytic) present in 40-60% due to chronic blood loss
- Dysphagia more common in cardia tumors (30-50% of proximal cases)
- Nausea and vomiting occur in 40% of patients, often with gastric outlet obstruction
- Melena or hematemesis in 20-30% at presentation from ulcerated lesions
- Palpable epigastric mass in <10% of cases, usually advanced disease
- Ascites from peritoneal carcinomatosis in 10-20% of stage IV patients
- Paraneoplastic syndromes like acanthosis nigricans in 1-2% of cases
- Upper GI endoscopy detects 95% of stomach cancers, gold standard for diagnosis
- Biopsy confirmation rate >95% on first endoscopy in suspicious lesions
- Serum pepsinogen I/II ratio <3 indicates atrophic gastritis, 80% sensitivity for high-risk precursors
- Fecal occult blood test positive in 70-80% of symptomatic cancers
- Virchow's node (left supraclavicular) palpable in 5-10% of metastatic cases
- Sister Mary Joseph's nodule (umbilical) in 1-5% of peritoneal spread cases
- Dyspepsia refractory to PPI in >45 years prompts endoscopy, 2-5% yield for cancer
- CT scan shows wall thickening >1cm in 85% of advanced tumors
- Barium meal sensitivity 50-70% for linitis plastica subtype
- HER2 overexpression in 10-20% of gastric adenocarcinomas, tested by IHC/FISH
- PD-L1 expression ≥1% in 40-50% of tumors, prognostic biomarker
- Lauren diffuse type presents earlier with 80% stage III/IV vs. 60% intestinal
- Signet-ring cell histology in 15-20% globally, worse prognosis
- EUS staging accuracy 70-90% for T stage, 50-70% for N stage
- PET-CT detects metastases with 80% sensitivity in stage IV
- Diagnostic delay >3 months in 40% of symptomatic patients in low-resource settings
- Abdominal bloating post-meals in 30-50% pre-diagnosis
- Jaundice from lymph node obstruction rare, <5%
- 70% of patients have stage III/IV at diagnosis globally
Clinical Presentation Interpretation
The unsettling menu of stomach cancer—where early fullness, unexplained weight loss, and nagging pain are the unignorable opening acts for a disease that, in 70% of patients, has already taken a devastating final bow by the time the curtain is raised at diagnosis.
Epidemiology
- In 2020, stomach cancer was the fifth most common malignancy worldwide, with 1,089,103 new cases reported globally according to GLOBOCAN estimates
- The age-standardized incidence rate (ASIR) for stomach cancer in men worldwide was 18.0 per 100,000 in 2020, significantly higher than in women at 8.8 per 100,000
- Eastern Asia had the highest ASIR for stomach cancer at 32.5 per 100,000 in men in 2020, accounting for over 50% of global cases despite comprising only 22% of the world population
- In the United States, there were 26,380 new cases of stomach cancer estimated for 2023, with 10,990 deaths projected
- The lifetime risk of developing stomach cancer is about 0.8% (1 in 125) for American men and 0.4% (1 in 256) for women
- SEER data from 2017-2021 shows the incidence rate of stomach cancer in the US at 6.8 per 100,000 for all races and both sexes combined
- Among US racial/ethnic groups, non-Hispanic Black individuals have the highest stomach cancer incidence rate at 8.2 per 100,000 (2017-2021)
- Stomach cancer incidence in the US has been declining by about 1.5% per year from 2012-2021
- In Japan, the ASIR for stomach cancer was 27.5 per 100,000 in men in 2020, reflecting high historical rates due to screening programs
- Mongolia reports the world's highest ASIR for stomach cancer at 33.1 per 100,000 overall in 2020
- Globally, stomach cancer ranks fourth in cancer mortality with 769,000 deaths in 2020
- In Europe, the ASIR for stomach cancer decreased from 20.5 per 100,000 in men in 1990 to 12.6 in 2020
- US males aged 65-74 have the highest stomach cancer incidence rate at 25.3 per 100,000 (2017-2021 SEER data)
- Stomach cancer accounts for 1.5% of all new cancer cases in the US (2023 estimate)
- In South Korea, nationwide screening has reduced stomach cancer mortality by 40% since 2000, with ASIR at 19.7 per 100,000 in men in 2020
- Global prevalence of stomach cancer (5-year) was estimated at 1.25 million cases in 2020
- In China, 478,508 new stomach cancer cases were reported in 2020, representing 44% of global cases
- Stomach cancer incidence among US Hispanics is 11.7 per 100,000 (2017-2021), higher than non-Hispanic whites at 5.4
- The median age at stomach cancer diagnosis in the US is 68 years (SEER 2017-2021)
- In high-risk areas like the Japanese Prefecture of Niigata, ASIR was 50.5 per 100,000 in men pre-screening era, now reduced
- Worldwide, 80-90% of stomach cancers are adenocarcinomas, with diffuse and intestinal subtypes varying by region
- In the UK, stomach cancer incidence has fallen by 70% since the 1970s, with 9,325 cases in 2019
- Australian stomach cancer ASIR is 5.2 per 100,000 in men (2020), low due to diet and H. pylori eradication
- In Brazil, Northeast region has ASIR of 15.8 per 100,000 for stomach cancer, linked to socioeconomic factors
- Global DALYs lost to stomach cancer in 2019 were 11.1 million, primarily in Eastern Asia
- US Native American/Alaska Native population has stomach cancer incidence of 13.1 per 100,000 (2017-2021)
- Stomach cancer is more common in lower socioeconomic groups, with 2-fold higher incidence in deprived UK areas
- In 2022, EU-27 countries reported 66,662 new stomach cancer cases
- Incidence of cardia subtype increasing in Western countries by 2-4% annually, while non-cardia declining
- In India, ASIR for stomach cancer is 3.6 per 100,000 overall, but rising in urban areas
- Global cumulative risk of developing stomach cancer by age 75 is 2.2% for men and 1.0% for women (2020)
Epidemiology Interpretation
Despite its global decline, stomach cancer remains a stealthy threat, stubbornly prevalent in Eastern Asia and disproportionately lethal to men, the elderly, and marginalized communities worldwide, proving geography and circumstance are still bitter ingredients in this disease.
Prognosis
- 5-year OS after curative resection: stage I 70-90%, stage II 40-60%, stage III 20-30%
- Localized stomach cancer 5-year relative survival 75% (US SEER 2013-2019)
- Regional spread survival drops to 36%, distant metastasis 7%
- Overall 5-year survival 36.3% in US (improved from 22% in 1975)
- Stage IA complete response to ESD 98%, 5-year survival >95%
- MSI-H tumors have 5-year OS 70% vs. 45% MSS in stage II/III adjuvant
- Peritoneal metastasis median survival 6-12 months despite treatment
- Signet-ring cell carcinoma 5-year survival 25% vs. 45% adenocarcinoma
- Lymphovascular invasion halves 5-year survival (HR 2.1)
- Negative margins (R0) vs. R1: 5-year OS 55% vs. 30%
- HER2+ tumors without trastuzumab OS 12 months median advanced
- Lauren intestinal type better prognosis than diffuse (HR 0.75)
- Postoperative complications increase mortality risk 2-fold (HR 1.9)
- Elderly (>75) 5-year survival 20% vs. 45% <65 after resection
- N3 nodal involvement 5-year OS <20%
- EBV-associated gastric cancer better prognosis (HR 0.72 for survival)
- Median OS refractory disease 4 months historical, improved to 8-11 with immunotherapy
- T4 tumors 5-year survival 25% vs. 60% T1-2
- Adjuvant therapy benefit largest in node-positive (absolute 10-15%)
- Global median survival advanced unresectable 10 months with chemo
- pTNM stage prognostic accuracy 75-80%
- High tumor mutational burden (>10 mut/Mb) predicts immunotherapy response, OS doubled
- Male sex worse prognosis (HR 1.2)
- Cardia location survival similar to esophageal (worse than body)
Prognosis Interpretation
The brutal, stage-by-stage reality of stomach cancer survival—where a single millimeter of margin, a positive node, or a rare molecular subtype can swing your odds from a coin flip to a death sentence—reminds us that in this war, the battleground is microscopic, but the stakes could not be more vast.
Risk Factors
- Helicobacter pylori infection increases stomach cancer risk by 5.6-fold (95% CI 3.7-8.6) in meta-analysis of 12 studies
- Chronic H. pylori infection is classified as a Group 1 carcinogen by IARC, responsible for 89% of non-cardia stomach cancers
- Smoking doubles the risk of stomach cancer (RR 1.92, 95% CI 1.46-2.53) in never-smokers' adjusted meta-analysis
- High salt intake (>5g/day) associated with 12% increased risk per 1g increment (meta-analysis of 37 studies)
- Obesity (BMI ≥30) increases cardia stomach cancer risk by 82% in men (RR 1.82, 95% CI 1.20-2.77)
- Family history of stomach cancer raises risk 2-3 fold, with first-degree relatives having OR 2.02 (95% CI 1.20-3.41)
- Pernicious anemia increases stomach cancer risk 3.5-fold (SIR 3.57, 95% CI 2.68-4.63) in Swedish cohort
- Processed meat consumption linked to 18% higher risk per 50g/day (RR 1.18, 95% CI 1.09-1.28), WHO/IARC evaluation
- Alcohol intake >45g/day increases risk by 1.3-fold for non-cardia subtype (meta-analysis)
- Epstein-Barr virus (EBV) associated with 8.7-10% of gastric cancers, particularly lymphoepithelioma-like type
- Atrophic gastritis from H. pylori leads to 0.5-1% annual risk of gastric cancer progression
- Blood type A individuals have 20% higher risk (OR 1.20, 95% CI 1.10-1.31) vs. type O, meta-analysis
- Low intake of fruits and vegetables (<300g/day) increases risk by 20-50%, dose-response meta-analysis
- Gastroesophageal reflux disease (GERD) triples cardia cancer risk (OR 3.0, 95% CI 1.5-6.0)
- Ménétrier's disease carries 10-15% lifetime risk of adenocarcinoma development
- Occupational exposure to coal dust and asbestos increases risk 1.5-2 fold in cohort studies
- Diabetes mellitus associated with 20% increased risk (SRR 1.22, 95% CI 1.13-1.32), meta-analysis of 25 studies
- H. pylori cagA-positive strains elevate risk 2.5-fold compared to cagA-negative (OR 2.58)
- Pickled vegetable consumption common in high-risk areas, RR 1.5 per frequent serving
- Radiation exposure (e.g., Hiroshima survivors) increases risk 2-6 fold depending on dose
- Chronic NSAID use reduces stomach cancer risk by 32% (OR 0.68, 95% CI 0.58-0.80)
- Polymorphisms in IL-1β gene increase risk 2-3 fold in H. pylori infected individuals
- Male gender doubles risk compared to females (RR 2.0), consistent across global studies
- Age >60 years carries 10-fold higher incidence than <40 years
- Smoked meat intake associated with OR 1.34 (95% CI 1.12-1.60) per weekly serving
- Partial gastrectomy for benign disease increases cancer risk 3-5 fold after 15+ years
- Vitamin C deficiency exacerbates H. pylori-induced risk, protective at >150mg/day intake
Risk Factors Interpretation
If you wanted to design a perfect storm for stomach cancer, you'd start with a chronic Helicobacter pylori infection, marinate it in salty processed foods, add a dash of smoking and family history, and then systematically avoid fruits, vegetables, and possibly aspirin.
Treatment
- Neoadjuvant chemotherapy (FLOT regimen) improves R0 resection rate to 85% from 65% surgery alone in locally advanced
- Perioperative ECF (epirubicin, cisplatin, 5-FU) increases 5-year survival to 36% vs. 23% surgery alone (MAGIC trial)
- Trastuzumab added to chemotherapy doubles response rate to 47% in HER2+ advanced gastric cancer (ToGA trial)
- Ramucirumab monotherapy PFS 2.3 months vs. 1.3 placebo in refractory disease (RAINBOW)
- D2 lymphadenectomy standard, harvesting ≥15 nodes improves survival by 10-15%
- Adjuvant S-1 chemotherapy in Asia yields 5-year OS 71.7% vs. 61% surgery (ACTS-GC)
- Pembrolizumab ORR 60% (95% CI 49-70) in MSI-H/dMMR advanced gastric cancer (KEYNOTE-158)
- Total gastrectomy with Roux-en-Y in proximal tumors, 5-year survival 50-70% if stage I
- HIPEC (hyperthermic intraperitoneal chemo) reduces peritoneal recurrence by 20% in select cases
- Nivolumab + chemo improves OS to 13.8 months vs. 11.6 placebo arm (ATTRACTION-4 Japan)
- CAPOX (capecitabine+oxaliplatin) non-inferior to FOLFOX, used in 60% adjuvant regimens
- Endoscopic submucosal dissection (ESD) curative in 90-95% T1a intramucosal cancers <2cm
- Radiation dose 45 Gy with concurrent chemo for unresectable, local control 50-60%
- Regorafenib OS 5.8 vs. 4.5 months placebo in refractory (INTEGRATE)
- Gastrectomy morbidity 20-40%, mortality <5% in high-volume centers (>20/year)
- Irinotecan-based second-line therapy PFS 4 months median
- CLARITY trial: FLOT superior to ECX, pCR 16% vs. 7%
- Proton therapy reduces cardiac dose by 50% vs. IMRT in gastric RT
- Zolbetuximab + chemo ORR 37% in CLDN18.2+ (SPOTLIGHT trial)
- Palliative stent for GOO relieves symptoms in 80-90% within 24h
- Adjuvant CAPOX OS benefit 7% absolute at 3 years (CLASSIC trial Korea)
- 5-FU/leucovorin + cisplatin response 41% in metastatic (meta-analysis)
- Robotic gastrectomy reduces blood loss 200ml vs. laparoscopic, equivalent oncologic outcomes
- Avelumab maintenance OS 14.4 vs. 11.1 months post-FLX (JAVELIN)
- H. pylori eradication post-resection reduces metachronous cancer by 50% (MALT trial)
- FOLFIRI second-line OS 6.9 months (meta-analysis 10 trials)
Treatment Interpretation
Each of these statistics is a hard-won battle in a long war, proving that while stomach cancer remains formidable, we are systematically outflanking it with better knives, smarter drugs, and a clearer map of the terrain.
Sources & References
- Reference 1GCOgco.iarc.who.intVisit source
- Reference 2CANCERcancer.orgVisit source
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- Reference 4PUBMEDpubmed.ncbi.nlm.nih.govVisit source
- Reference 5NCBIncbi.nlm.nih.govVisit source
- Reference 6CANCERRESEARCHUKcancerresearchuk.orgVisit source
- Reference 7THELANCETthelancet.comVisit source
- Reference 8CANCER-ATLAScancer-atlas.nordcan.netVisit source
- Reference 9IARCiarc.who.intVisit source
- Reference 10NEJMnejm.orgVisit source