Gastric Cancer

The stomach lies between the esophagus and small intestine and helps store, mix, and begin the digestion of food.

Most stomach cancers are adenocarcinomas arising from glandular cells in the stomach lining. This page focuses on gastric adenocarcinoma rather than other stomach tumors such as lymphoma or gastrointestinal stromal tumor, which require different treatment approaches.

Gastric cancer can arise in different parts of the stomach. Tumors near the gastroesophageal junction may sometimes require treatment planning that incorporates principles used for gastroesophageal junction cancer.

A diagnosis of gastric cancer does not automatically mean that the entire stomach must be removed. The extent of treatment depends on tumor location, depth of invasion, lymph node involvement, and whether the cancer has spread.

Gastric cancer usually results from a combination of infection, genetic susceptibility, long-term changes in the stomach lining, and lifestyle factors.

Helicobacter pylori infection is one of the most important modifiable risk factors. Long-term infection can lead to chronic gastritis, gastric atrophy, intestinal metaplasia, and eventually gastric cancer in some people. Treating H. pylori infection can reduce future gastric cancer risk in selected populations.

Other risk factors include increasing age, smoking, diets high in salted or smoked foods, chronic atrophic gastritis, intestinal metaplasia, pernicious anemia, some Epstein-Barr virus–associated gastric cancers, a family history of gastric cancer, and certain inherited cancer syndromes.

Hereditary diffuse gastric cancer is associated with inherited alterations in genes such as CDH1 and CTNNA1. Lynch syndrome, familial adenomatous polyposis, and several other inherited syndromes can also increase gastric cancer risk.

Early gastric cancer may cause no noticeable symptoms, and when symptoms occur they can resemble common digestive problems.

Possible symptoms include upper abdominal discomfort or pain, indigestion, early satiety, loss of appetite, nausea or vomiting, bloating, unexplained weight loss, fatigue or anemia, black stools, or vomiting blood.

Tumors near the upper stomach or gastroesophageal junction may also cause difficulty swallowing.

These symptoms are often caused by conditions other than cancer, but persistent or worsening symptoms—particularly when accompanied by weight loss, anemia, bleeding, or difficulty swallowing—should be medically evaluated.

Upper endoscopy with biopsy is the cornerstone of gastric cancer diagnosis.

Endoscopy allows doctors to directly inspect the stomach lining and collect tissue from suspicious areas. Pathologic examination confirms the diagnosis and provides information about tumor type and biologic features.

After diagnosis, additional tests are used for staging.

Contrast-enhanced CT is commonly used to evaluate local disease, lymph nodes, and distant metastases.

Endoscopic ultrasound can help determine the depth of invasion and regional lymph node involvement in selected localized tumors.

PET/CT is not required for every patient but may be useful in selected staging situations.

Staging laparoscopy may be recommended for some potentially resectable, locally advanced cancers to identify small peritoneal metastases that may not be visible on imaging.

Biomarker Testing

Biomarker testing has become an important part of treatment planning, particularly for unresectable, recurrent, or metastatic gastric adenocarcinoma.

Key biomarkers include HER2, PD-L1, mismatch repair deficiency or microsatellite instability, and CLDN18.2.

HER2 can identify patients who may benefit from HER2-targeted therapy. PD-L1, commonly reported as a combined positive score, can help guide immunotherapy decisions. dMMR/MSI-H tumors are particularly sensitive to immune checkpoint inhibition, while CLDN18.2 has become an important therapeutic target in advanced gastric cancer.

Treatment for gastric cancer depends on the tumor stage, location, whether complete resection is possible, pathological type, biomarkers, and the patient's overall physical condition.

Early Gastric Cancer

Some very early gastric cancers confined to the mucosa or superficial submucosa and associated with a low risk of lymph node spread can be treated endoscopically.

Common procedures include endoscopic submucosal dissection and, in selected situations, endoscopic mucosal resection.

Pathology after endoscopic treatment determines whether removal is considered curative or whether additional surgery is needed.

Resectable Gastric Cancer

For resectable gastric cancer requiring surgery, the goal is complete removal of the tumor together with appropriate regional lymph node dissection.

Depending on tumor location and extent, surgery may involve distal, proximal, or total gastrectomy. Removal of the entire stomach is not necessary for every patient.

For locally advanced resectable disease, surgery alone is generally not sufficient. Perioperative chemotherapy—treatment given both before and after surgery—is an important strategy, with FLOT representing a major modern regimen.

In East Asian practice, postoperative chemotherapy following adequate D2 gastrectomy is also an established strategy for appropriate stage II or III disease, with regimens such as CAPOX or S-1 supported by clinical trials.

Radiation Therapy

Radiation therapy is not routinely required before or after surgery for every patient with gastric cancer.

Chemoradiation may be considered in selected situations, such as inadequate surgical resection or lymph node dissection, concern about local residual disease, unresectable local disease, or relief of symptoms such as bleeding or pain.

Modern treatment more commonly relies on surgery combined with perioperative or postoperative systemic chemotherapy for appropriately resectable disease.

Advanced or Metastatic Gastric Cancer

Treatment of advanced gastric cancer is now strongly influenced by biomarker results rather than chemotherapy alone.

Before first-line therapy, testing for HER2, PD-L1, MMR/MSI, and CLDN18.2 can directly affect treatment selection.

For HER2-negative advanced disease, fluoropyrimidine- and platinum-based chemotherapy remains an important backbone and may be combined with immune checkpoint inhibition in appropriate patients. Pembrolizumab plus chemotherapy is FDA-approved for HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

For HER2-positive disease, trastuzumab remains an important targeted therapy. For tumors with PD-L1 CPS of at least 1, pembrolizumab combined with trastuzumab and chemotherapy is FDA-approved as first-line treatment.

For HER2-negative, CLDN18.2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, zolbetuximab combined with fluoropyrimidine- and platinum-containing chemotherapy is another first-line option.

Supportive Care

Supportive care is important throughout gastric cancer treatment, not only at the end of life.

Patients may experience poor appetite, weight loss, malnutrition, anemia, nausea, or difficulty eating because of the cancer, surgery, or systemic treatment.

After partial or total gastrectomy, patients may need dietary adjustments and monitoring for deficiencies such as iron or vitamin B12.

When advanced disease causes bleeding, gastric outlet obstruction, or pain, treatments such as endoscopic stenting, surgical bypass, radiation therapy, or other supportive procedures may be used.

Palliative care can be provided together with active anticancer treatment and focuses on symptom relief, nutrition, function, and quality of life.