Key Facts

Gastric cancer has high mortality due to late presentation. H. pylori eradication is a key preventive strategy.

Epidemiology

• ~6,600 new cases/year in the UK; ~4,300 deaths/year
• Male:female ratio 2:1
• Incidence declining in the West (falling H. pylori prevalence); very common in East Asia
• Median age: 70 years

Aetiology

• H. pylori: chronic infection → chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma
• Diet: smoked/salted foods, low fruit/vegetable intake
• Smoking: 1.5-2× risk
• Family history: 2-3× risk; hereditary diffuse gastric cancer (CDH1 mutation — prophylactic gastrectomy)
• Pernicious anaemia: atrophic gastritis → 2-3× risk
• Previous gastric surgery: bile reflux → increased risk after 15-20 years

Pathophysiology

• Intestinal type: well-formed glandular structures; Correa cascade (H. pylori → chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma)
• Diffuse type: poorly cohesive cells, signet ring morphology; CDH1 (E-cadherin) loss; infiltrative growth (linitis plastica)
• Spread: direct invasion (peritoneum), lymphatic (perigastric nodes), haematogenous (liver, lung), transcoelomic (peritoneal — Krukenberg tumours in ovaries, Sister Joseph's nodule at umbilicus)

Early Disease

• Often asymptomatic or vague dyspepsia
• Epigastric discomfort
• Early satiety, loss of appetite

Advanced Disease

• Progressive dysphagia (GOJ tumours)
• Weight loss (significant)
• Nausea and vomiting (if outlet obstruction)
• GI bleeding (haematemesis, melaena, iron deficiency anaemia)
• Palpable epigastric mass

Metastatic Signs

• Virchow's node (left supraclavicular — Troisier's sign)
• Sister Mary Joseph's nodule (periumbilical metastasis)
• Krukenberg tumour (ovarian metastases — bilateral)
• Blumer's shelf (palpable mass on rectal examination — pouch of Douglas deposits)
• Ascites (peritoneal carcinomatosis)

Red Flags

• Dysphagia (any age)
• Age ≥55 with weight loss and upper GI symptoms
• Iron deficiency anaemia in male or post-menopausal female
• Palpable epigastric mass
• Virchow's node

Bedside

• Abdominal examination
• Lymph node palpation (supraclavicular, periumbilical)
• DRE (Blumer's shelf)

Bloods

• FBC (anaemia), U&Es, LFTs, albumin
• CEA, CA 19-9 (monitoring, not diagnostic)

Imaging

• OGD with biopsy: gold standard (multiple biopsies from mass and surrounding mucosa)
• CT chest/abdomen/pelvis: TNM staging
• EUS: T and N staging
• PET-CT: detects occult metastases
• Staging laparoscopy + peritoneal washings: mandatory for potentially operable gastric cancer (detects peritoneal disease missed on CT in 20-30%)

Special Tests

• HER2 testing: all advanced gastric/GOJ adenocarcinomas
• PD-L1 CPS: guides immunotherapy eligibility
• MSI/dMMR testing: immunotherapy eligibility
• H. pylori testing and eradication

Non-pharmacological

• MDT discussion
• Nutritional support (dietitian, supplementary feeds)
• H. pylori eradication if positive
• Psychological support

Pharmacological

• Resectable disease: perioperative FLOT × 4 pre-op + 4 post-op (FLOT4 trial; superior to ECF/ECX)
• Metastatic — first-line: platinum + fluoropyrimidine (cisplatin or oxaliplatin + 5-FU or capecitabine)
  • HER2+: add trastuzumab (ToGA trial)
  • PD-L1 CPS ≥5: add nivolumab (CheckMate-649)
• Second-line: ramucirumab (anti-VEGFR2) + paclitaxel (RAINBOW trial)
• MSI-high metastatic: pembrolizumab
• MALT lymphoma (H. pylori-associated): H. pylori eradication can cure early-stage disease

Surgical/Interventional

• Subtotal gastrectomy: distal tumours (2/3 resection with D2 lymphadenectomy)
• Total gastrectomy: proximal/diffuse tumours (with Roux-en-Y reconstruction)
• D2 lymphadenectomy: standard in specialist centres (removes perigastric + coeliac axis nodes)
• Endoscopic resection (EMR/ESD): for T1a, well-differentiated, <2cm, no ulceration
• Palliative stenting: GOJ obstruction
• Palliative gastrectomy/bypass: in selected patients with bleeding or obstruction

Referral Criteria

• Suspected gastric cancer: 2-week wait referral for OGD
• All confirmed cancers: upper GI cancer MDT
• Hereditary diffuse gastric cancer (CDH1): genetics referral (consider prophylactic gastrectomy)

• Stage I: 5-year survival >70%
• Stage II: 5-year survival 45-55%
• Stage III: 5-year survival 20-35%
• Stage IV (metastatic): median survival 10-14 months with chemotherapy
• Overall 5-year survival: approximately 20% (most present late)
• FLOT4: median OS 50 months with perioperative FLOT (vs 35 months with ECF/ECX)
• HER2+ with trastuzumab: median OS 13.8 months (vs 11.1 without)
• Japan/South Korea: much higher survival due to screening programmes (>60% 5-year survival)
• MALT lymphoma (H. pylori+): >90% cure with eradication therapy for localised disease

Lauren Classification

Key Trials in Gastric Cancer