Stomach Cancer (Gastric Cancer) — Causes, Staging, Surgery & Chemotherapy Guide — Symptoms, Causes & Treatment | MyMedicPlus

Stomach cancer (gastric cancer) is a malignancy arising from the gastric mucosa — approximately 95% are adenocarcinomas (gastric adenocarcinoma). It is the 5th most common cancer globally (1.09 million new cases annually — World Cancer Research Fund, 2022) and the 4th leading cause of cancer-related death, accounting for approximately 769,000 deaths per year worldwide. Incidence is highest in East Asia (particularly South Korea, Japan, China, Mongolia), Eastern Europe, and parts of South America; Japan has been a global leader in early detection through national screening programmes resulting in over 50% of cases detected at early stage — contributing to 5-year survival rates above 70% in Japan, compared to approximately 20% in the UK and United States where the majority present with advanced disease. Gastric cancer is classified by the Lauren classification into two major histological types: intestinal type (well-differentiated, glandular structure, more common in high-risk populations, associated with H. pylori chronic infection and dietary risk factors, tends to occur in older males) and diffuse type (poorly differentiated, lacks glandular structure, signet ring cells dispersed in stroma, infiltrates the gastric wall — causing linitis plastica pattern, more common in younger patients, women, associated with E-cadherin/CDH1 mutations, worse prognosis). Tumour location is important: non-cardia gastric cancers (body and antrum) are predominantly H. pylori-driven; gastro-oesophageal junction (GOJ) cancers (Siewert type II-III) are epidemiologically similar to gastric cancers but distinct from oesophageal cancers (Siewert type I — oesophageal adenocarcinoma driven by Barrett's and GORD). The majority (80%+) of UK cases present at advanced (T3-T4 or metastatic) stage because early gastric cancer causes no specific symptoms — underscoring the need for prompt upper GI endoscopy in patients with alarm features.

Helicobacter pylori infection: the most important modifiable risk factor for non-cardia gastric cancer — classified as a definite Group I carcinogen by the International Agency for Research on Cancer (IARC); present in approximately 90% of non-cardia gastric cancers; infection triggers chronic active gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → invasive carcinoma (Correa cascade); risk of gastric cancer in H. pylori-infected individuals is 1-6% over a lifetime — absolute risk is low but population attributable fraction is very high; eradication of H. pylori significantly reduces subsequent gastric cancer risk (meta-analyses show 30-50% reduction). Dietary risk factors: high intake of salt-preserved foods (salted fish, pickled vegetables — nitrosamines formed from nitrites are carcinogenic; Japanese and Korean high-salt diets historically associated with high incidence); smoked meats; high-nitrate foods; low intake of fresh fruit and vegetables (low antioxidant vitamins C and E intake — relative risk 1.5-2.0 for low fruit/vegetable intake). Tobacco smoking: relative risk approximately 1.5-2.5 for non-cardia gastric cancer. Alcohol: modest independent risk factor. Obesity: primarily associated with GOJ/cardia gastric cancer — reflux and Barrett's-like changes at the gastro-oesophageal junction. Prior gastric surgery: partial gastrectomy (Billroth II reconstruction) increases risk of gastric remnant cancer approximately 15-20 years later — through reflux of bile and alkaline contents. Genetic risk factors: hereditary diffuse gastric cancer (HDGC) — germline CDH1 (E-cadherin) mutations — autosomal dominant; cumulative risk of diffuse gastric cancer 70-80% by age 80 in CDH1 mutation carriers; BRCA2 mutations also associated; Lynch syndrome (hereditary non-polyposis colorectal cancer — MLH1, MSH2 mutations) — 1-13% lifetime risk of gastric cancer; familial adenomatous polyposis (APC mutations). First-degree family history of gastric cancer: 2-3-fold increased risk. Pernicious anaemia: loss of intrinsic factor, achlorhydria, and atrophic autoimmune gastritis — moderate gastric cancer risk. Ménétrier's disease (giant hypertrophic gastropathy): rare pre-malignant condition.

Early gastric cancer (confined to mucosa and submucosa) is typically asymptomatic or causes only vague upper abdominal discomfort — which is why 80%+ of UK patients present with advanced disease. The majority of symptoms that bring patients to medical attention are 'alarm features' associated with locally advanced or metastatic disease. Dysphagia (difficulty swallowing): particularly for GOJ (gastro-oesophageal junction) tumours causing progressive obstruction — initially to solids, then liquids; distal gastric cancers cause outlet obstruction. Persistent dyspepsia (upper abdominal discomfort, indigestion, nausea): new-onset dyspepsia in patients above 55 is an NICE 2-week-wait urgent referral indication (NG12). Unintentional weight loss: due to cachexia (tumour-related cytokine release — particularly IL-6 and TNF-alpha), reduced oral intake from dysphagia or early satiety, and malabsorption. Early satiety and postprandial fullness: from linitis plastica (diffuse infiltration reducing gastric capacity and wall compliance — the 'leather bottle stomach'). Epigastric pain: dull, persistent, not consistently related to meals — may radiate to the back if posterior gastric wall or pancreas invaded. Haematemesis (vomiting blood) or melaena (black tarry stools): from tumour ulceration — may present with acute GI bleeding or iron deficiency anaemia. Nausea and vomiting (gastric outlet obstruction): in pyloric or antral tumours — bile-free vomiting of undigested food hours after eating. Iron deficiency anaemia: unexplained iron deficiency anaemia in men of any age and post-menopausal women — urgently requires OGD (oesophago-gastro-duodenoscopy) to exclude upper GI cancer. Virchow's node: palpable left supraclavicular lymph node — Troisier's sign — indicates advanced metastatic disease via the thoracic duct. Sister Mary Joseph nodule: periumbilical metastatic deposit. Krukenberg tumour: ovarian metastasis from signet-ring cell gastric cancer. Abdominal mass (palpable epigastric mass) and signs of peritoneal disease (ascites, Blumer's shelf — rectal shelf of peritoneal deposits felt on rectal examination).

Oesophago-gastro-duodenoscopy (OGD — upper GI endoscopy): the definitive diagnostic test — visual inspection of the gastric mucosa, identification of lesions, and multiple biopsy specimens (a minimum of 6-8 biopsies are taken from the lesion and surrounding mucosa — increasing the sensitivity of the pathological diagnosis). Histology from OGD biopsy confirms adenocarcinoma, with Lauren classification (intestinal vs. diffuse). H. pylori testing: urea breath test or histological assessment of biopsy (CLO test — Campylobacter-like organism test). Staging investigations: CT chest, abdomen, and pelvis with IV and oral contrast: primary T staging assessment and distant metastasis detection (liver — most common site of haematogenous spread; peritoneum; lung; lymph node stations); CT has approximately 80% sensitivity for lymph node metastases and 90%+ for distant metastases; identifies resectability — involvement of aorta, coeliac axis, superior mesenteric vessels, pancreas head indicates unresectability. Endoscopic ultrasound (EUS): superior to CT for T-stage (depth of wall invasion — particularly distinguishing T1a/T1b/T2) and regional lymph node assessment (N-stage); essential for staging early gastric cancer and guiding endoscopic vs. surgical resection decision. PET-CT (FDG-PET-CT): useful for detecting occult distant metastases and assessing treatment response; not all gastric cancers are FDG-avid (diffuse/signet-ring cell poorly FDG-avid). Staging laparoscopy: performed immediately before planned curative gastrectomy — identifies peritoneal metastases in 15-30% of patients deemed resectable by CT (peritoneal lavage cytology — positive cytology indicates M1 disease even without visible peritoneal deposits). Biomarker testing: HER2 (ERBB2) testing: immunohistochemistry (IHC 0, 1+, 2+, 3+) and FISH/ISH for equivocal IHC 2+ results — HER2-positive (IHC 3+ or IHC 2+/FISH-positive) — approximately 15-20% of gastric cancers — is predictive of response to trastuzumab; mandatory testing in all advanced gastric cancer. PD-L1 CPS (combined positive score): CPS 5 or above predicts response to nivolumab (CheckMate-649 trial); MSI testing (microsatellite instability — dMMR): MSI-high/dMMR gastric cancers have particularly high response rates to anti-PD-1 immunotherapy. Blood tests: FBC (anaemia — normocytic or microcytic iron deficiency); LFTs (hepatic metastases); albumin (nutritional status — hypoalbuminaemia is a poor prognostic marker); CEA and CA19-9 (tumour markers — not diagnostic but useful for monitoring treatment response and recurrence).

Curative-intent treatment (localised disease): Endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR): for early gastric cancer (EGC) meeting strict criteria — mucosal (T1a) lesions without ulceration and below 2 cm diameter (or larger differentiated lesions meeting expanded criteria); ESD achieves en-bloc resection with curative intent — 5-year survival above 95% for mucosal EGC. Surgical resection: total gastrectomy (proximal tumours — body and proximal stomach) with Roux-en-Y reconstruction; subtotal gastrectomy (distal tumours — antrum and pylorus) — equivalent oncological outcomes with better nutritional outcomes for distal tumours; D2 lymphadenectomy (systematic removal of perigastric and regional lymph nodes — minimum 16 lymph nodes examined) — the current surgical standard (Dutch randomised trial demonstrated survival benefit of D2 vs. D1 at 15 years); radical surgery at a high-volume upper GI centre improves outcomes. Perioperative chemotherapy (the standard of care for resectable T2-T4 gastric cancer in the UK): FLOT regimen (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, 5-fluorouracil 2600 mg/m2 continuous infusion) — 4 cycles before and 4 cycles after surgery; FLOT4 trial demonstrated superior 5-year OS (45% vs. 36%) vs. ECF/ECX perioperative chemotherapy (the previous MAGIC trial standard); FLOT is the current UK standard of care for resectable gastric cancer. Adjuvant chemotherapy (post-surgery only in patients unable to receive perioperative treatment): capecitabine plus oxaliplatin (XELOX/CAPOX — CLASSIC trial: Asian population; shown to improve DFS). Adjuvant chemoradiotherapy: considered for patients with T3-T4 or node-positive disease following surgery without perioperative chemotherapy (MacDonald/INT 0116 regimen — bolus 5-FU/leucovorin plus 45 Gy radiotherapy). Advanced/metastatic gastric cancer: HER2-positive (IHC 3+ or 2+/FISH+): first-line trastuzumab (8 mg/kg loading, 6 mg/kg Q3W) plus FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil) or CAPOX — ToGA trial: improved median OS from 11.1 to 13.8 months. HER2-negative, PD-L1 CPS 5 or above: nivolumab (PD-1 inhibitor) plus chemotherapy (FOLFOX or CAPOX) — CheckMate-649 trial: improved median OS from 11.6 to 13.8 months and 3-year OS rate 22% vs. 12%; particularly dramatic response in MSI-high/dMMR tumours (2-year OS approximately 40%). HER2-positive with confirmed progression on trastuzumab: trastuzumab deruxtecan (T-DXd — DESTINY-Gastric01 and 02 trials — ADC with 10 payload of deruxtecan per antibody — response rate approximately 45%; approved FDA 2021 and NICE 2022). Second-line: ramucirumab (VEGFR2 monoclonal antibody — REGARD trial) ± paclitaxel; irinotecan-based regimens. Palliative care: symptom management for dysphagia (self-expanding metal stent — SEMS), gastric outlet obstruction (duodenal stenting or surgical bypass), pain, nausea; palliative chemotherapy to maintain quality of life and extend survival in fit patients (ECOG PS 0-2); early palliative care involvement.

Gastric outlet obstruction: antral or pyloric tumours causing progressive obstruction leading to nausea, vomiting, and dehydration; managed with duodenal/pyloric self-expanding metal stent (SEMS) as a palliative procedure (2-4 week stent patency) or surgical gastrojejunostomy bypass (longer durability). Upper GI bleeding: from tumour ulceration — haematemesis or melaena; acute haemostasis with endoscopic therapy (adrenaline injection, thermal coagulation, haemoclip) or interventional radiology embolisation; tumour infiltration of major vessels (left gastric artery) may require emergency surgery. Peritoneal carcinomatosis: seeding of malignant cells to the peritoneal surface — causing ascites (malignant ascites — 15-30% of gastric cancer patients), bowel obstruction from peritoneal deposits, and pain; therapeutic paracentesis for symptomatic ascites; median survival after peritoneal metastasis development is approximately 4-6 months with systemic chemotherapy. Malnutrition and cachexia: tumour-related metabolic changes (elevated IL-6, TNF-alpha, proteolysis-inducing factor) combined with reduced oral intake, dysphagia, and post-gastrectomy malabsorption; requires nutritional support — dietitian-led oral supplementation (high-protein, calorie-dense), nasogastric or percutaneous endoscopic gastrostomy (PEG) feeding in patients unable to maintain oral intake; total parenteral nutrition (TPN) for bowel obstruction. Post-gastrectomy complications: dumping syndrome (early — rapid transit of hyperosmolar food into the small bowel causing fluid shift, nausea, abdominal pain, and diarrhoea 15-30 minutes after eating; late — reactive hypoglycaemia 1-3 hours post-meal from rapid glucose absorption and insulin surge); vitamin B12 deficiency (loss of intrinsic factor after total gastrectomy — requires lifelong intramuscular hydroxocobalamin 1 mg every 3 months); iron deficiency (malabsorption — requires oral or IV iron replacement); calcium and vitamin D deficiency; bone disease (osteoporosis from malabsorption — DEXA monitoring and supplementation). Recurrence: approximately 50% of resected gastric cancer patients develop recurrence — peritoneal (the most common site of recurrence), liver, and lymph node metastases; surveillance CT at 6-monthly intervals for 3 years after curative resection.

Helicobacter pylori eradication: the most important preventive intervention for intestinal-type non-cardia gastric cancer; H. pylori eradication in infected individuals reduces gastric cancer risk by 30-50% (meta-analyses including the IARC Working Group 2014 conclusions); eradication should be offered to all symptomatic H. pylori-positive patients; population-level screening and treatment programmes (as implemented in Japan, South Korea, and Taiwan) are projected to further reduce incidence. Standard first-line eradication: triple therapy — PPI (omeprazole 20 mg BD or lansoprazole 30 mg BD) plus amoxicillin 1 g BD plus clarithromycin 500 mg BD for 7-14 days (14 days superior); bismuth-based quadruple therapy (PPI, bismuth, metronidazole, tetracycline) for clarithromycin-resistant areas or second-line after triple therapy failure — NICE recommends confirmation of eradication with urea breath test 4-6 weeks after completing therapy. Dietary modification: increased consumption of fresh fruits and vegetables (particularly vitamin C-rich — oranges, tomatoes, peppers — which inhibit nitrosamine formation); reduced salt-preserved, smoked, and processed meat intake; Mediterranean diet pattern associated with lower gastric cancer risk. Smoking cessation: reduces gastric cancer risk by 30-40% — all patients should be advised and supported to stop smoking. Genetic counselling and prophylactic gastrectomy for CDH1 mutation carriers: patients with germline CDH1 (E-cadherin) mutations who meet IGCLC (International Gastric Cancer Linkage Consortium) criteria should be offered prophylactic total gastrectomy between ages 20-30 (before cancer development); MRI and endoscopic surveillance as an interim measure; CDH1 mutation testing should be offered to families meeting IGCLC clinical criteria (2+ first-degree relatives with diffuse gastric cancer, at least one diagnosed below 50). Aspirin/NSAID use: observational studies show 30-40% risk reduction for gastric cancer — mechanism involves H. pylori and COX-2 inflammation inhibition; not currently recommended specifically for gastric cancer prevention but benefits in cardiovascular prevention may be relevant to shared decision-making. Monitoring at-risk patients: patients with chronic atrophic gastritis, intestinal metaplasia, or low-grade dysplasia on gastric biopsy should be enrolled in surveillance endoscopy programmes per BSG guidelines (every 3 years for extensive intestinal metaplasia; annually for low-grade dysplasia).

Seek urgent GP appointment or use NHS 2-week-wait pathway for: dysphagia (difficulty swallowing) — always requires urgent OGD regardless of age; unexplained iron deficiency anaemia (any man or post-menopausal woman with iron deficiency unexplained by clear dietary history or menstrual loss); upper abdominal mass on examination; persistent vomiting lasting more than 1-2 weeks; and new-onset dyspepsia in patients above 55 — NICE NG12 recommends urgent referral for all patients above 55 with unexplained dyspepsia plus any of: weight loss, anaemia, dysphagia, vomiting, or iron deficiency. Haematemesis (vomiting blood), melaena (black tarry stools), or fresh rectal bleeding with haemodynamic instability: call 999 or go to A&E immediately — acute upper GI bleeding is an emergency requiring immediate resuscitation and urgent endoscopy. For patients with known gastric cancer: contact oncology team or GP urgently for: worsening difficulty swallowing or eating (possible tumour progression or stent blockage); sudden severe abdominal pain (possible perforation or haemorrhage — emergency); increased abdominal distension or inability to pass stool or flatus (possible bowel obstruction from peritoneal disease); and any signs of systemic infection (fever, confusion) during chemotherapy treatment (possible neutropenic sepsis — an oncological emergency requiring same-day assessment and IV antibiotics).