Gastric Cancer
Gastric cancer, or stomach cancer, is a malignancy arising from the tissues of the stomach, most commonly from the glandular cells of its inner lining. It develops slowly in most cases, often over years, and produces few distinctive symptoms in its early stages—which is the principal reason it is frequently diagnosed only once it has advanced. Incidence varies dramatically around the world, with rates in parts of East Asia many times those in North America, and this variation has driven very different approaches to screening and to how often the disease is caught early. Helicobacter pylori infection is the single most important modifiable cause. Treatment has changed considerably in recent years, with endoscopic removal now possible for the earliest cancers and molecular testing increasingly guiding therapy for advanced disease.
What is it?
The stomach receives swallowed food, mixes it with acid and enzymes, and passes it into the small intestine. Its wall has an inner mucosa containing the glands that produce acid, mucus, and digestive enzymes, a submucosa, a muscular layer, and an outer serosa. Gastric cancer arises when cells in this wall—most often the glandular cells of the mucosa—acquire genetic changes that allow uncontrolled growth and invasion into deeper layers.
More than nine in ten stomach cancers are adenocarcinomas, arising from glandular cells. The remainder comprise gastrointestinal stromal tumors, neuroendocrine tumors, and lymphomas, which are distinct diseases with different treatments and are covered separately. The term gastric cancer generally refers to adenocarcinoma unless specified otherwise.
Adenocarcinoma is classically divided into two types with meaningfully different behavior.
The intestinal type forms recognizable glandular structures and typically develops through a well-described sequence of changes over many years: chronic inflammation from Helicobacter pylori infection, progressive loss of the normal gastric glands known as atrophic gastritis, replacement of gastric lining with intestinal-type cells known as intestinal metaplasia, then dysplasia, and finally cancer. This stepwise progression is the basis of screening and surveillance programs, since each stage can be identified and the later ones monitored. Intestinal type is more common in older patients, in men, and in high-incidence regions.
The diffuse type behaves quite differently. Cells lack cohesion and spread within the stomach wall rather than forming a discrete mass, often including signet ring cells, so named because a large internal mucin droplet displaces the nucleus to one edge. When this infiltration stiffens a large portion of the stomach, the result is linitis plastica—a rigid, thickened, poorly distending organ sometimes described as a leather bottle stomach. Diffuse type occurs in younger patients more often, shows no sex predominance, is less clearly linked to the H. pylori sequence, is more likely to be hereditary, and carries a worse prognosis. Crucially, it can be missed on both endoscopy and imaging, because the surface lining may look near-normal while disease spreads beneath it.
Location matters as well. Cancers of the gastric cardia, at the junction with the esophagus, behave differently from those of the body and antrum, are more closely associated with reflux and obesity than with H. pylori, and have increased in some Western populations even as overall gastric cancer rates have fallen.
The causes and risk factors are relatively well characterized.
Helicobacter pylori infection is the dominant modifiable cause and is classified as a definite carcinogen. It drives the chronic inflammation that initiates the intestinal-type sequence. Most infected people never develop cancer, but the infection accounts for a large share of cases worldwide, and eradication reduces subsequent risk—most substantially when it occurs before atrophic changes are established.
Dietary factors include high intake of salt and salt-preserved, smoked, and pickled foods, and low intake of fresh fruit and vegetables. The widespread adoption of refrigeration is thought to have contributed substantially to the historical decline in incidence.
Smoking increases risk in a dose-dependent way. Heavy alcohol consumption contributes. Obesity is particularly associated with cancers near the gastroesophageal junction.
Medical conditions that raise risk include autoimmune atrophic gastritis and pernicious anemia, prior partial gastrectomy performed decades earlier, gastric adenomatous polyps, and Ménétrier disease. Epstein-Barr virus is associated with a distinct molecular subtype of gastric cancer.
Hereditary factors account for a small but important minority. Hereditary diffuse gastric cancer, caused by mutations in the CDH1 gene, carries a high lifetime risk of diffuse gastric cancer and an increased risk of lobular breast cancer in women. Because surveillance endoscopy detects diffuse disease poorly, risk-reducing total gastrectomy is discussed with mutation carriers. Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome, and Li-Fraumeni syndrome also carry increased risk. A family history of gastric cancer, particularly diffuse type or in young relatives, warrants consideration of genetic assessment.
Symptoms in early disease are minimal or absent, and when present are typically indistinguishable from common indigestion. This overlap is the central clinical problem: dyspepsia is extremely common and almost always benign, so the challenge is identifying which patients warrant endoscopy without investigating everyone.
As disease progresses, symptoms include persistent upper abdominal pain or discomfort, indigestion that does not respond to usual treatment, early satiety, bloating, nausea, and reduced appetite. Unintentional weight loss is a significant feature. Slow bleeding produces iron deficiency anemia with fatigue, breathlessness, and pallor, and unexplained iron deficiency in an adult—particularly a man or a postmenopausal woman—is itself an indication for endoscopic evaluation. Overt bleeding produces vomited blood or black tarry stools.
Obstruction of the stomach outlet causes vomiting of undigested food and severe early satiety. Tumors near the esophageal junction cause difficulty swallowing. Advanced disease may produce a palpable upper abdominal mass, abdominal swelling from ascites, jaundice, and an enlarged node above the left collarbone.
Diagnosis and staging follow a defined sequence.
Upper endoscopy with biopsy is definitive. It permits direct inspection, targeted biopsy, and assessment of the background mucosa for atrophy, intestinal metaplasia, and H. pylori. Multiple biopsies are standard, since a single sample may miss cancer—especially in diffuse-type disease where the surface can look deceptively normal and repeat or deeper sampling may be needed when suspicion persists despite negative results.
Endoscopic ultrasound assesses how deeply the tumor invades the wall and evaluates nearby lymph nodes. It is particularly important when endoscopic resection is being considered, since eligibility depends on the tumor being confined to specific layers.
CT of the chest, abdomen, and pelvis with intravenous contrast is central to staging, identifying local extension, enlarged lymph nodes, liver metastases, ascites, and peritoneal disease. Adequate gastric distension improves assessment.
PET-CT is used selectively. Its recognized limitation is that signet ring cell, mucinous, and many diffuse-type tumors are frequently not FDG-avid, so a negative scan does not exclude disease in those subtypes.
Diagnostic laparoscopy is performed before major surgery in many centers because CT misses small peritoneal deposits, which are common in gastric cancer and change treatment fundamentally. Peritoneal washings may be taken for cytology at the same time, since free cancer cells in the abdomen affect staging and treatment even without visible deposits.
Molecular and biomarker testing has become an essential part of diagnosis rather than an optional extra. Testing typically includes HER2 status, PD-L1 expression, mismatch repair or microsatellite instability status, and increasingly CLDN18.2 expression and Epstein-Barr virus status. These results directly determine which targeted and immune therapies are available.
Blood tests support assessment: complete blood count and iron studies, liver and kidney function, albumin and nutritional markers. Tumor markers including CEA and CA 19-9 lack the sensitivity and specificity for diagnosis and are used mainly for monitoring.
Screening differs markedly by country. Japan and South Korea operate national screening programs using endoscopy or contrast studies, and as a result diagnose a far higher proportion of cancers at an early, curable stage. Most Western countries do not screen the general population because incidence is too low for it to be cost-effective, and instead focus on surveillance of higher-risk individuals—those with extensive atrophic gastritis or intestinal metaplasia, gastric adenomas, pernicious anemia, hereditary syndromes, or a significant family history. This difference in approach substantially explains the survival differences reported between regions.
Important to Know
Gastric cancer outcomes depend heavily on stage at diagnosis, and the gap between early and advanced disease is wide—early cancers confined to the mucosa are frequently curable, sometimes without major surgery, while advanced disease is treated with different goals. Care is coordinated by a multidisciplinary team including gastroenterology, surgical oncology, medical oncology, radiology, pathology, genetics, dietetics, and palliative care.
Endoscopic resection is possible for a defined group of very early cancers. Endoscopic submucosal dissection removes the tumor from within the stomach, preserving the organ entirely. Eligibility depends on strict criteria including depth of invasion, size, histologic type, and absence of ulceration or lymphovascular invasion. Where criteria are met, outcomes are comparable to surgery with far less morbidity. This approach is used extensively in countries with screening programs and is available at specialist centers elsewhere.
Surgery remains the primary curative treatment for localized disease beyond endoscopic criteria. The operation is a partial or total gastrectomy depending on tumor location and extent, combined with removal of the regional lymph nodes. The extent of lymph node dissection, described as D1 or D2, influences outcomes, and a D2 dissection performed by experienced surgeons is standard in most guidelines. Minimally invasive and robotic approaches are increasingly used for appropriate tumors.
Chemotherapy given both before and after surgery has become standard for locally advanced disease in most Western practice, improving outcomes compared with surgery alone. Giving treatment before surgery also allows assessment of how the tumor responds, which carries prognostic information. In some regions and situations, chemotherapy after surgery alone or chemoradiotherapy is preferred, and practice varies.
Treatment of advanced and metastatic disease has changed substantially. Systemic chemotherapy remains the backbone, but molecular testing now opens additional options: HER2-targeted therapy for HER2-positive tumors, immunotherapy for tumors with high PD-L1 expression or mismatch repair deficiency, and agents targeting CLDN18.2 for tumors expressing it. Mismatch repair deficient and microsatellite instability high tumors in particular can respond notably well to immunotherapy. These options make comprehensive biomarker testing at diagnosis important rather than something to consider later.
Nutrition is central and often underestimated. Reduced intake, obstruction, treatment side effects, and the metabolic effects of cancer all contribute to weight loss and weakness, which in turn reduce tolerance of treatment. Dietitian involvement from diagnosis is valuable. Patients who have had part or all of the stomach removed face lasting changes: smaller more frequent meals, and lifelong monitoring and replacement of vitamin B12, iron, calcium, and vitamin D. Dumping syndrome, in which food passes too rapidly into the small intestine causing cramping, diarrhea, and lightheadedness after eating, is common after gastrectomy and is managed with dietary modification.
Managing obstruction is an important part of care in advanced disease. Options include endoscopic stent placement, a bypass operation, or a venting tube, chosen according to the situation and the patient’s goals rather than by a fixed rule.
Palliative care involvement improves quality of life and is appropriately introduced alongside active treatment rather than only when treatment ends. It covers symptom control, nutritional and psychological support, and help with decision-making.
Genetic assessment deserves specific mention. Diffuse gastric cancer in a young patient, multiple affected relatives, or a family history combining gastric and lobular breast cancer should prompt referral for genetic counseling. Identifying a CDH1 mutation has major implications not only for the patient but for relatives, who can be tested and offered risk-reducing options.
Prevention is achievable to a meaningful degree. Helicobacter pylori testing and eradication reduce risk, most effectively when performed before atrophic changes develop, and eradication is recommended for anyone found to be infected who has a family history of gastric cancer or existing precancerous changes. Stopping smoking, moderating alcohol, reducing salt-preserved and processed foods, increasing fresh fruit and vegetable intake, and maintaining a healthy weight all contribute. For those with identified precancerous changes, endoscopic surveillance at intervals determined by the extent of those changes allows early detection.
Follow-up after treatment involves clinical review, imaging, endoscopy where relevant, and nutritional monitoring, on schedules determined by the treatment received and the risk of recurrence.
Care is coordinated by a multidisciplinary team, and second opinions at high-volume centers are reasonable, since outcomes for gastric cancer surgery are associated with surgical and institutional volume. Imaging, endoscopic, pathological, molecular, and clinical findings are interpreted together alongside the patient’s overall health and goals rather than in isolation.
Patient education plays an important role. Understanding why endoscopy rather than imaging establishes the diagnosis, why molecular testing is done at the outset, why some early cancers can be removed endoscopically, what life after gastrectomy involves nutritionally, why family members may need genetic assessment, and which symptoms warrant prompt contact with the treating team all contribute to appropriate care and informed decision-making.
Red flag symptoms include difficulty or pain on swallowing; persistent vomiting, particularly of undigested food; vomiting blood or material resembling coffee grounds; black tarry stools; unintentional weight loss; persistent upper abdominal pain; new or worsening early satiety; unexplained iron deficiency anemia with fatigue or breathlessness; a palpable upper abdominal mass; progressive abdominal swelling; jaundice; and new persistent indigestion beginning in a patient over the age of about 55 or accompanied by any of the above. These warrant prompt medical evaluation and generally an upper endoscopy.