Gastric Cancer: Risk Factors, Diagnosis and Treatment

Gastric Cancer: Risk Factors, Diagnosis and Treatment

In IARC’s GLOBOCAN 2022 estimates, gastric cancer (stomach cancer) accounted for approximately 968,000 new cases and 660,000 deaths worldwide, ranking fifth for both incidence and cancer mortality. The geographic distribution is strikingly unequal: East Asia — particularly China, Japan, and South Korea — accounts for approximately 60% of all global gastric cancer cases. China alone contributes approximately 40% of worldwide gastric cancer incidence.

Gastric cancer may be diagnosed after it has grown beyond the earliest stage. Some locally advanced, resectable cancers can still be treated with curative intent; metastatic disease is a different treatment setting. The 5-year survival for localised gastric cancer exceeds 60–70%; for metastatic disease, it remains below 10% — making early detection by endoscopy the most impactful strategy in high-incidence regions.

Anatomy and Cancer Types

The stomach is divided into the cardia (adjacent to the oesophago-gastric junction), fundus (upper left), body (corpus), antrum (lower), and pylorus (junction with duodenum). Cancer location affects prognosis and treatment:

• Gastric adenocarcinoma — accounts for >90% of all gastric cancers; arises from glandular epithelial cells; the focus of this guide
• Gastro-oesophageal junction (GOJ) / cardia cancers — anatomically and biologically distinct; treatment similar to oesophageal cancer
• Gastric lymphoma (MALT) — mucosa-associated lymphoid tissue lymphoma; closely linked to H. pylori; often cured by H. pylori eradication alone
• Gastrointestinal stromal tumour (GIST) — arises from interstitial cells of Cajal or related precursor cells. Surgery is central for suitable localized, resectable disease; targeted treatment such as imatinib depends on tumour molecular characteristics, recurrence risk and stage, and is not appropriate for every GIST

Causes and Risk Factors

Helicobacter pylori (H. pylori)

H. pylori is the dominant cause of non-cardia gastric cancer — a gram-negative spiral bacterium that colonises the gastric mucosa, triggering chronic inflammation, atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately adenocarcinoma (the Correa cascade). H. pylori infection is estimated to be responsible for approximately 89% of non-cardia gastric cancers worldwide.

The World Health Organization classified H. pylori as a Group 1 (definite) carcinogen. Approximately 50% of the global population is infected; prevalence reaches 50–70% in China. Eradication with antibiotics + proton pump inhibitor reduces gastric cancer risk by approximately 35–40%.

Diet

• High salt intake — disrupts gastric mucosal defences; the very high salt diet in traditional East Asian cuisine (pickled vegetables, salted fish, fermented foods) correlates with regional gastric cancer rates
• Nitrosamines — formed from nitrates in smoked, cured, and processed meats
• Low fruit and vegetable intake — antioxidant vitamins C and E are protective
• Alcohol — modest dose-dependent association

Other Risk Factors

• Age — most cases occur >60; median diagnosis age approximately 68
• Male sex — 2× higher incidence in men
• Smoking — approximately 1.5–2× increased risk
• First-degree family history — 2–3× increased risk; hereditary diffuse gastric cancer (CDH1 gene mutation) carries very high lifetime risk in affected families
• Atrophic gastritis and intestinal metaplasia — pre-malignant conditions detectable by endoscopy; surveillance depends on their extent and individual risk factors rather than being automatic for every patient
• Pernicious anaemia — autoimmune gastritis destroying parietal cells; raises gastric cancer risk 3–6×
• Prior gastric surgery — post-gastrectomy stump cancer risk increases after 15–20 years
• Obesity — particularly for cardia/GOJ cancers

Symptoms

Early gastric cancer is almost always asymptomatic — or produces only non-specific dyspepsia indistinguishable from gastritis or peptic ulcer disease. This is why endoscopic screening is crucial in high-risk populations.

Symptoms of locally advanced gastric cancer:

• Persistent upper abdominal pain or discomfort — epigastric pain not relieved by antacids
• Unintentional weight loss — often substantial (5–10+ kg) by the time of diagnosis
• Anorexia — progressive loss of appetite
• Dysphagia — difficulty swallowing (cardia or GOJ tumours)
• Early satiety — feeling full after small amounts of food (linitis plastica — diffuse infiltrative cancer stiffening the stomach)
• Nausea and vomiting — particularly with pyloric obstruction
• Iron deficiency anaemia — chronic occult bleeding
• Haematemesis or melaena — visible upper GI bleeding (less common at presentation)
• Palpable abdominal mass — advanced disease
• Signs of metastasis: Virchow's node (left supraclavicular lymph node); Sister Mary Joseph nodule (periumbilical metastasis); Krukenberg tumour (ovarian metastasis)

Alarm features needing prompt medical assessment: the urgency and choice of investigation depend on the symptoms and clinical findings, not a universal age-over-45 rule. Active vomiting of blood, black stools with faintness or other signs of significant bleeding require emergency assessment. Other concerning features include:

• Unintentional weight loss
• Dysphagia
• Progressive difficulty eating
• Persistent vomiting
• Iron deficiency anaemia
• Haematemesis

Diagnosis

Upper GI Endoscopy (Gastroscopy)

The essential diagnostic investigation. A flexible endoscope is passed under conscious sedation through the mouth into the stomach and duodenum. The gastric mucosa is systematically inspected, and any suspicious lesion is biopsied.

Advanced endoscopic techniques improve detection of early gastric cancer:

• Narrow-band imaging (NBI) — highlights mucosal vascular patterns
• Chromoendoscopy — spraying indigo carmine or acetic acid delineates lesion margins
• Magnification endoscopy — high-magnification assessment of mucosal pit patterns

H. pylori Testing

Patients with gastric cancer or relevant precancerous conditions should be assessed for H. pylori infection and offered eradication treatment when infection is established. Tests for active infection include a ¹³C-urea breath test, stool antigen testing and appropriate gastric biopsy tests. Antibody serology may remain positive after eradication and does not by itself establish active infection. The clinician chooses the test and its timing, including the effects of medicines on accuracy.

Staging

Once gastric adenocarcinoma is diagnosed histologically:

CT chest/abdomen/pelvis — identifies locoregional lymph node involvement and distant metastases (liver, peritoneum, lungs). The most important staging test.

Endoscopic ultrasound (EUS) — high-frequency ultrasound through the endoscope assesses depth of invasion (T stage) and perigastric lymph node involvement (N stage); critical for selecting patients for endoscopic resection vs surgery.

PET-CT — useful to exclude occult distant metastases in patients planned for curative surgery; less sensitive for peritoneal disease.

Diagnostic laparoscopy — with peritoneal washings for cytology, can detect peritoneal metastases not seen on CT. Its use depends on stage, risk of peritoneal spread and the planned treatment: Pan-Asian ESMO guidance recommends it for patients with resectable cancer who are candidates for perioperative chemotherapy, and advises considering it selectively before upfront surgery according to the risk of peritoneal metastasis.

Molecular profiling on biopsy:

• HER2 (ERBB2) status — 12–20% of gastric cancers overexpress HER2; indicates eligibility for trastuzumab (anti-HER2 antibody) in advanced disease
• MMR/MSI testing — microsatellite instability-high (MSI-H) tumours respond well to immunotherapy (pembrolizumab)
• PD-L1 (CPS score) — predicts benefit from immune checkpoint inhibitors

TNM Staging and Prognosis

The following are AJCC 8th-edition pathological stage groups, with M0 unless stated. Clinical and post-neoadjuvant staging must be interpreted separately by the oncology team.

Stage	T/N combinations
IA	T1N0
IB	T1N1; T2N0
IIA	T1N2; T2N1; T3N0
IIB	T1N3a; T2N2; T3N1; T4aN0
IIIA	T2N3a; T3N2; T4aN1–2; T4bN0
IIIB	T1–2N3b; T3–4aN3a; T4bN1–2
IIIC	T3–4aN3b; T4bN3a–3b
IV	Any T/N with M1 (distant metastasis)

T describes invasion depth, N regional lymph nodes and M distant spread. Stage-specific survival depends on the population, period and treatment; this table is not an individual prognosis calculator.

Treatment

Endoscopic Resection (Early Gastric Cancer)

Endoscopic resection is considered for selected early cancers with sufficiently low lymph-node risk. Depth alone is insufficient: size, ulceration, histological differentiation and lymphovascular invasion matter. The resection specimen must be assessed for margins and curability; some findings require additional surgery.

Endoscopic mucosal resection (EMR) — cap-assisted snare resection; for small, flat lesions ≤2 cm.

Endoscopic submucosal dissection (ESD) — dissection within the submucosal layer permits removal of a lesion in one piece. It can be curative for appropriately selected early cancers, but bleeding, perforation and other adverse effects are possible. Selection criteria and specialist expertise determine suitability; absence of impact on quality of life cannot be guaranteed.

Surgery

Total gastrectomy — removal of the entire stomach with lymph node dissection; used for proximal, body, or diffuse cancers.

Distal (subtotal) gastrectomy — preserves the upper stomach; preferable for distal cancers; equivalent oncological outcomes with better nutritional tolerance.

D2 lymph node dissection — the surgical standard in East Asia (removing the second-tier of regional lymph nodes); associated with lower local recurrence and improved survival compared to limited D1 dissection.

Minimally invasive approaches: laparoscopic or robotic gastrectomy may be options for selected patients; suitability depends on stage, planned resection, patient factors and surgical expertise. Evidence differs by technique and procedure, so equivalent cancer control and faster recovery should not be assumed for every resectable tumour or for both approaches.

Perioperative Chemotherapy

For resectable non-metastatic gastric cancer (stage IB–III):

FLOT (docetaxel + oxaliplatin + leucovorin + 5-FU) is a perioperative chemotherapy option for suitable resectable gastric or gastro-oesophageal junction adenocarcinoma. In FLOT4, median overall survival was 50 months with FLOT versus 35 months with ECF/ECX (hazard ratio 0.77). The estimated five-year overall survival was 45% versus 36%; the 50-month median must not be confused with a 50% five-year survival rate. The trial included resectable cT2-or-higher or node-positive disease without distant metastases; its results are not an individual prognosis.

Neoadjuvant chemotherapy is given before planned surgery and may shrink a tumour and inform assessment of treatment response. Some initially unresectable tumours may become resectable after systemic treatment, but this is a selected-case decision after reassessment; conversion to resectability and cure are not guaranteed.

Adjuvant chemotherapy — post-surgical S-1 (oral fluoropyrimidine) or capecitabine + oxaliplatin (CAPOX) — standard in East Asian guidelines (particularly for D2-resected patients).

Advanced/Metastatic Gastric Cancer

First-line trial evidence:

• Nivolumab plus FOLFOX/CAPOX — CheckMate 649 enrolled previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction or oesophageal adenocarcinoma. In the PD-L1 CPS ≥5 primary population, median overall survival was 14.4 versus 11.1 months with chemotherapy alone.
• Trastuzumab plus chemotherapy — in HER2-positive advanced gastric or gastro-oesophageal junction cancer, ToGA reported median overall survival of 13.8 versus 11.1 months with chemotherapy alone.
• Trastuzumab deruxtecan (T-DXd) is a later-line option in eligible HER2-positive disease after prior trastuzumab-based treatment under applicable local authorisation.

These trial comparisons concern different populations and are not a comparison between the medicines. Current regimen selection, biomarkers, prior treatment and local approval must be checked by the oncology team.

Immunotherapy: MSI-H/dMMR and PD-L1 results can inform treatment selection, but do not by themselves establish the appropriate drug, combination or line of therapy. Pembrolizumab may be an option under the applicable indication. Nivolumab plus ipilimumab did not meet the prespecified overall-survival significance threshold versus chemotherapy in CheckMate 649’s CPS ≥5 population; it should not be presented here as a routine gastric-cancer regimen based solely on MSI-H or CPS ≥10.

Gastric Cancer Care in China

Before arranging gastric cancer care in China, ask the receiving team to confirm:

• The indicated endoscopy, biopsy and staging tests.
• Whether EMR, ESD, gastrectomy or another approach is suitable, and the team’s relevant experience.
• Which molecular tests are needed and how results influence treatment.
• The exact systemic regimen, local authorisation, availability and adverse-effect monitoring; medicines in the same class are not automatically biosimilars.
• The H. pylori treatment and test-of-cure plan, if indicated.
• An itemised hospital quote, separate coordination scope, language support and follow-up arrangements.

Contact a PriumCare care navigator to arrange a gastroscopy, gastric cancer assessment, or treatment consultation.

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Sources for these targeted corrections

• NCI gastric cancer treatment and pathological staging.
• FLOT4 primary trial.
• Cancer Institute NSW eviQ FLOT evidence summary.
• CheckMate 649 primary report.
• ToGA primary trial.
• CheckMate 649 nivolumab/ipilimumab analysis.
• Japanese Gastric Cancer Treatment Guidelines.
• NICE suspected cancer referral guidance.

Editorial source correction: 25 October 2026. This targeted check addressed flagged staging, trial results, test capabilities, treatment and surveillance claims. It is not a clinical review of the whole article. No named medical reviewer is claimed. Original publication date is retained.

Additional targeted source clarification

Editorial source check: 25 October 2026. These changes concern specific statistics and treatment-selection statements, not a whole-article medical review.

• Source 1
• Source 2
• Source 3
• Source 4
• Source 5

Targeted staging-laparoscopy and surgical-approach clarification

Editorial source check: 26 October 2026. This checks only the staging-laparoscopy indication and minimally invasive surgery statement clarified above; it is not a whole-article medical review and adds no named clinical reviewer. The original publication date is retained.

• Pan-Asian ESMO: selected staging laparoscopy and peritoneal cytology
• Japanese gastric cancer guidelines 2025: laparoscopic and robotic surgical selection