Stomach Cancer

The most common stomach cancer is gastric adenocarcinoma. It may arise in the gastric cardia, body, antrum, or at the gastroesophageal junction. Pathologists may describe intestinal-type or diffuse-type morphology, and modern molecular classifications provide additional biological information.

Gastric lymphoma, gastrointestinal stromal tumor, and neuroendocrine tumors are biologically different diseases and should not be merged into a gastric adenocarcinoma page.

• Upper abdominal discomfort, pain, or burning
• Early satiety, reduced appetite, or bloating
• Nausea or vomiting
• Difficulty swallowing, especially with tumors near the gastroesophageal junction
• Black stools, vomiting blood, or iron-deficiency anemia
• Unexplained weight loss and fatigue
• In advanced disease, ascites, jaundice, or an abdominal mass

Early gastric cancer may be asymptomatic or cause only nonspecific indigestion-like symptoms.

• Chronic Helicobacter pylori infection
• Chronic atrophic gastritis, intestinal metaplasia, pernicious anemia, and selected precancerous gastric conditions
• Smoking
• Dietary patterns high in salt-preserved, pickled, or smoked foods
• Gastric adenomatous polyps or a history of partial gastrectomy
• A family history of gastric cancer
• CDH1-associated hereditary diffuse gastric cancer
• Lynch syndrome, familial adenomatous polyposis, and other inherited conditions
• Epstein-Barr virus in a subset of gastric cancers
• Obesity and gastroesophageal reflux in cancers near the cardia or gastroesophageal junction

Risk varies substantially by region, H. pylori prevalence, family history, and gastric mucosal changes.

• Routine population screening is not generally recommended in low-incidence regions.
• In high-incidence countries or regions, upper endoscopy may be incorporated into organized screening programs.
• Age and interval should follow local policy.
• People with strong family history, inherited syndromes, severe atrophy, or extensive intestinal metaplasia may need individualized endoscopic surveillance.
• Testing for and eradicating H. pylori reduces gastric cancer risk in some populations.
• Prevention includes not smoking, reducing highly salted and preserved foods, eating a balanced diet rich in fresh produce, and managing H. pylori and premalignant gastric conditions.
• People from hereditary diffuse gastric cancer families need specialist genetic counseling; ordinary endoscopy cannot completely eliminate risk.

Diagnosis is discussed within the Overview, Screening, Staging, and Biomarkers sections above for this cancer type. Specific tests depend on presentation, site, and pathology.

TNM staging focuses on depth of invasion through the stomach wall, regional lymph nodes, and distant metastasis.

Early gastric cancer is defined by invasion limited to the mucosa or submucosa, regardless of regional lymph-node status; this is not the same as having early symptoms.

Histologic grade describes differentiation.

Lauren classification commonly distinguishes intestinal and diffuse types.

Staging laparoscopy and peritoneal washings can identify occult peritoneal disease in selected locally advanced cancers.

H. pylori can promote a sequence of chronic inflammation, atrophy, intestinal metaplasia, dysplasia, and cancer.

Diffuse gastric cancers often involve abnormal cell adhesion.

Modern molecular studies identify groups such as Epstein-Barr virus-associated, microsatellite unstable, chromosomally unstable, and genomically stable tumors. HER2, PD-L1, mismatch repair/MSI, and CLDN18.2 have direct treatment relevance in advanced disease.

• HER2
• PD-L1, commonly reported with the combined positive score (CPS)
• MMR proteins and/or MSI
• CLDN18.2
• NTRK fusions, which are rare
• Broader genomic testing in selected advanced cancers
• FGFR2b and additional targets as active research areas, with routine use depending on trial evidence and regional approval

Gastric cancers can be heterogeneous. Results may differ between parts of the primary tumor and between primary and metastatic sites.

• HER2
  Human Epidermal Growth Factor Receptor 2

• Highly selected superficial cancers may be treated with endoscopic mucosal resection or endoscopic submucosal dissection.
• Resectable cancer may require partial or total gastrectomy with appropriate lymph-node dissection, combined with perioperative or postoperative chemotherapy depending on region, stage, and practice.
• Postoperative chemoradiation is used in selected settings.
• Unresectable or metastatic disease is treated primarily with systemic therapy, selected according to HER2, PD-L1, MSI/MMR, CLDN18.2, prior treatment, and general health.
• Supportive procedures and palliative care may address bleeding, obstruction, pain, anemia, and malnutrition.

• Chemotherapy: fluorouracil, capecitabine, oxaliplatin, cisplatin, docetaxel, paclitaxel, and irinotecan
• HER2-directed therapy: trastuzumab; later-line fam-trastuzumab deruxtecan in selected HER2-positive disease
• Immunotherapy: pembrolizumab, nivolumab, and other regionally approved agents according to biomarker status, HER2 status, and treatment line
• CLDN18.2-directed therapy: zolbetuximab with fluoropyrimidine- and platinum-containing chemotherapy for eligible HER2-negative, CLDN18.2-positive advanced disease in approved regions
• Antiangiogenic therapy: ramucirumab, alone or with paclitaxel in selected later-line settings

• Gastrectomy: weight loss, early satiety, dumping syndrome, bile reflux, anemia, and deficiencies of vitamin B12, iron, folate, calcium, or vitamin D
• Chemotherapy: bone marrow suppression, nausea, diarrhea, neuropathy, and mucositis
• Immunotherapy: immune-related toxicities involving multiple organs
• Trastuzumab: possible cardiac dysfunction
• Antibody-drug conjugates: bone marrow suppression, nausea, and interstitial lung disease, depending on the agent
• Zolbetuximab: nausea, vomiting, and infusion-related reactions may require proactive management
• Supportive care should include early oncology nutrition, small frequent meals, micronutrient monitoring, anemia treatment, antiemetics, pain care, and psychosocial support.

Persistent vomiting, inability to eat or drink, black stools, vomiting blood, or rapidly worsening abdominal swelling needs prompt assessment.

• CLDN18.2-directed antibodies, bispecific antibodies, and cell therapies are major research areas.
• Studies are examining HER2 heterogeneity, HER2-low expression, and new antibody-drug conjugates.
• Perioperative immunotherapy is being tested for resectable gastric cancer.
• Circulating tumor DNA and peritoneal cell-free tumor DNA are being studied for recurrence risk.
• EBV, MSI, and immune microenvironment subtypes may support more precise treatment selection.
• A major U.S. regulatory example is FDA approval in October 2024 of zolbetuximab with chemotherapy for first-line treatment of CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

• Where exactly is the tumor, and does it involve the gastroesophageal junction?
• What are the pathologic type, grade, and TNM stage?
• Do I need staging laparoscopy and peritoneal washings?
• Have HER2, PD-L1, MMR/MSI, and CLDN18.2 been tested?
• Am I a candidate for endoscopic resection, surgery, or preoperative chemotherapy?
• How much of the stomach would be removed, and how would that change eating long term?
• How will weight loss and nutrient deficiency be prevented?
• Do I need H. pylori treatment, and should family members be assessed?
• Does the pattern suggest an inherited gastric cancer syndrome?
• Are there clinical trials for my biomarker profile?