Key Facts

Gastric cancer is a major global health burden. Despite declining incidence in the UK, it remains a leading cause of cancer-related death due to late presentation.

Epidemiology

Approximately 6,700 new cases per year in the UK. Male:female ratio 2:1. Incidence increases with age (peak 70-80 years). Strong geographic variation — highest rates in East Asia, Eastern Europe, South America. UK incidence has halved over the past 40 years (declining H. pylori prevalence, better food preservation). However, proximal/GOJ tumours are increasing.

Aetiology

• H. pylori infection: most important risk factor for non-cardia gastric cancer (3-6x risk)
• Dietary: high salt intake, nitrosamines (processed meats), smoked foods; protective factors include fresh fruit and vegetables
• Smoking: 1.5-2x risk
• Pernicious anaemia: autoimmune atrophic gastritis → 3-6x risk
• Previous partial gastrectomy: stump carcinoma (20-30 year latency)
• Genetic: CDH1 mutation (hereditary diffuse gastric cancer — prophylactic gastrectomy indicated), Lynch syndrome, FAP, Li-Fraumeni
• Blood group A: 20% increased risk

Pathophysiology

Intestinal type follows the Correa cascade: H. pylori-driven chronic gastritis → multifocal atrophic gastritis → intestinal metaplasia → dysplasia → invasive adenocarcinoma. Environmental factors (salt, nitrosamines) and genetic susceptibility (IL-1β polymorphisms) modulate progression.

Diffuse type (including signet ring cell/linitis plastica): loss of E-cadherin (CDH1 gene) causes loss of cell-cell adhesion, allowing tumour cells to infiltrate diffusely through the gastric wall. More common in younger patients and has a worse prognosis.

Early Disease

• Often asymptomatic or non-specific dyspepsia
• May be detected incidentally at OGD

Advanced Disease

• Weight loss (most common presenting symptom — up to 60%)
• Dyspepsia/epigastric pain (50%)
• Dysphagia (proximal/GOJ tumours)
• Nausea and vomiting (especially pyloric tumours)
• Early satiety (linitis plastica — reduced gastric distensibility)
• GI bleeding: haematemesis, melaena, iron deficiency anaemia

Metastatic Disease

• Virchow's node (left supraclavicular lymphadenopathy — Troisier's sign)
• Sister Mary Joseph nodule (periumbilical metastasis)
• Krukenberg tumour (ovarian metastasis — particularly signet ring cell)
• Blumer's shelf (palpable rectal shelf on DRE — peritoneal deposit in pouch of Douglas)
• Ascites (peritoneal carcinomatosis)
• Hepatomegaly (liver metastases)

Red Flags

• Any dysphagia (urgent OGD regardless of age)
• Age ≥55 with weight loss + upper abdominal pain/reflux/dyspepsia → urgent 2WW referral
• Palpable epigastric mass
• Unexplained iron deficiency anaemia

Bedside

• OGD + multiple biopsies: diagnostic — minimum 8 biopsies from ulcer rim and base
• Nutritional assessment: weight, BMI, albumin

Bloods

• FBC: iron deficiency anaemia
• LFTs: liver metastases
• U&Es, albumin: nutritional/renal status
• CEA, CA19-9, CA72-4: tumour markers (limited sensitivity; useful for monitoring)
• HER2 status: on biopsy specimen (if positive — trastuzumab eligible)
• PD-L1 CPS, MSI/dMMR: immunotherapy eligibility

Imaging

• CT thorax/abdomen/pelvis with contrast: initial staging
• PET-CT: assess for distant metastases, response to neoadjuvant therapy
• Endoscopic ultrasound (EUS): T-staging and lymph node assessment
• Staging laparoscopy + peritoneal washings: essential before curative surgery — detects occult peritoneal disease in ~20% with normal CT

Special Tests

• Molecular profiling: HER2, PD-L1, MSI, FGFR2, Claudin 18.2 — guide targeted therapy
• Hereditary cancer gene testing: CDH1 if diffuse gastric cancer <50 years or family history

Non-pharmacological

• Upper GI cancer MDT discussion: all cases
• Nutritional support: dietitian, NG/NJ feeding or parenteral nutrition if needed
• Pre-habilitation: exercise and nutritional optimisation before surgery
• Psychological support: cancer nurse specialist

Pharmacological

• Perioperative chemotherapy (curative intent):
  • FLOT (5-FU, leucovorin, oxaliplatin, docetaxel): 4 cycles pre-op + 4 cycles post-op — current standard (FLOT4 trial)
  • Previously ECF/ECX (MAGIC trial)
• Trastuzumab: add to chemotherapy if HER2-positive (IHC 3+ or FISH+) — ToGA trial
• Nivolumab + chemotherapy: first-line for advanced/metastatic with CPS ≥5 (CheckMate 649)
• Palliative chemotherapy: FOLFOX, capecitabine + oxaliplatin; median survival ~10-12 months
• Ramucirumab (anti-VEGFR2): second-line ± paclitaxel (RAINBOW trial)

Surgical/Interventional

• Subtotal gastrectomy: distal tumours (antrum/body) with 5 cm proximal margin
• Total gastrectomy: proximal tumours, linitis plastica, diffuse type
• D2 lymphadenectomy: standard of care (≥16 lymph nodes for adequate staging)
• Endoscopic resection (EMR/ESD): for early gastric cancer (T1a, well-differentiated, <2 cm, no ulceration)
• Palliative stenting: for GOJ obstruction
• Palliative bypass/jejunostomy: for gastric outlet obstruction

Referral Criteria

• 2WW referral: alarm features per NICE NG12
• All confirmed gastric cancers to upper GI cancer MDT
• Genetics referral if diffuse gastric cancer <50 years or family history (CDH1 testing)

Overall 5-year survival is approximately 20%. Stage-dependent: Stage IA ~70-80%, Stage IB ~50-60%, Stage II ~30-40%, Stage III ~10-20%, Stage IV <5%. FLOT perioperative chemotherapy improved median overall survival from 35 to 50 months compared to ECF/ECX. Complete pathological response to neoadjuvant chemotherapy occurs in ~15-20%. Linitis plastica/signet ring cell histology carries a particularly poor prognosis. Hereditary diffuse gastric cancer (CDH1 mutation carriers) has lifetime gastric cancer risk of ~70% — prophylactic total gastrectomy recommended.

Gastric Cancer Staging (Simplified TNM 8th Edition)

Key Trials