Stomach Cancer: Causes, Symptoms, Treatment and Prognosis — Overview, Diagnosis & Treatment Options | MyMedicPlus

Gastric (stomach) cancer is the fifth most common cancer and the fourth leading cause of cancer death worldwide, with approximately 1 million new cases annually. Adenocarcinoma accounts for over 90% of cases. Two molecular subtypes: intestinal (associated with H. pylori, chronic atrophic gastritis) and diffuse (including signet ring cell, associated with CDH1 mutations, worse prognosis).

Helicobacter pylori (H. pylori) infection is the most important risk factor, causing approximately 89% of non-cardia gastric cancers through chronic inflammation and intestinal metaplasia. Additional risk factors: salt-preserved and smoked foods, smoking, alcohol, low vitamin C intake, pernicious anemia, and previous gastric surgery. Germline CDH1 mutations cause hereditary diffuse gastric cancer (lifetime risk >70%).

Early symptoms: dyspepsia, epigastric discomfort, early satiety, and loss of appetite. Advanced disease: significant weight loss, anemia, dysphagia (cardiac/gastroesophageal junction tumors), hematemesis, melena, palpable epigastric mass. Classic metastatic signs: Virchow's node (left supraclavicular lymphadenopathy), Krukenberg tumor (ovarian metastasis), and Sister Mary Joseph nodule (umbilical metastasis).

Upper endoscopy with biopsy (minimum 6 biopsies for diffuse-type) is the diagnostic standard. CT chest/abdomen/pelvis with IV contrast for staging. EUS for T and N staging. Diagnostic laparoscopy to exclude occult peritoneal disease before planned resection. HER2 testing (IHC/FISH), MSI/MMR status, PD-L1 (CPS scoring), FGFR2, and claudin 18.2 (CLDN18.2) testing guide systemic therapy selection.

Resectable disease: perioperative FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, docetaxel) plus D2 total or subtotal gastrectomy is the standard in Europe and increasingly worldwide. HER2-positive advanced: trastuzumab plus chemotherapy plus nivolumab. Advanced/metastatic first-line: nivolumab plus FOLFOX or FLOT; CLDN18.2-positive: zolbetuximab plus mFOLFOX6; MSI-H: pembrolizumab.

Stage I: 5-year survival approximately 90%. Stage II: approximately 65%. Stage III: approximately 30-40%. Stage IV: approximately 5-10%. Overall 5-year survival approximately 32%. Japan and South Korea achieve significantly better outcomes due to endoscopic screening programs that detect early-stage disease. HER2-positive and MSI-H tumors have improved prognosis with targeted therapy.