Gastric Cancer Treatment (PDQ®)


Information for: Patients | Healthcare Professionals

General Information About Gastric Cancer

Gastric cancer is a disease in which malignant (cancer) cells form in the lining of the stomach.

The stomach is a J-shaped organ in the upper abdomen. It is part of the digestive system, which processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) in foods that are eaten and helps pass waste material out of the body. Food moves from the throat to the stomach through a hollow, muscular tube called the esophagus. After leaving the stomach, partly-digested food passes into the small intestine and then into the large intestine.

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, large intestine, and small intestine. 
The stomach and esophagus are part of the upper digestive system.

 

The wall of the stomach is made up of 3 layers of tissue: the mucosal (innermost) layer, the muscularis (middle) layer, and the serosal (outermost) layer. Gastric cancer begins in the cells lining the mucosal layer and spreads through the outer layers as it grows.

Stromal tumors of the stomach begin in supporting connective tissue and are treated differently from gastric cancer. See the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.

For more information about cancers of the stomach, see the following PDQ summaries:

  • Unusual Cancers of Childhood
  • Stomach (Gastric) Cancer Prevention
  • Stomach (Gastric) Cancer Screening

Age, diet, and stomach disease can affect the risk of developing gastric cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for gastric cancer include the following:

  • Having any of the following medical conditions:
    • Helicobacter pylori (H. pylori) infection of the stomach.
    • Chronicgastritis (inflammation of the stomach).
    • Pernicious anemia.
    • Intestinalmetaplasia (a condition in which the normal stomach lining is replaced with the cells that line the intestines).
    • Familial adenomatous polyposis (FAP) or gastricpolyps.
     
  • Eating a diet high in salted, smoked foods and low in fruits and vegetables.
  • Eating foods that have not been prepared or stored properly.
  • Being older or male.
  • Smoking cigarettes.
  • Having a mother, father, sister, or brother who has had stomach cancer.

Symptoms of gastric cancer include indigestion and stomach discomfort or pain.

These and other signs and symptoms may be caused by gastric cancer or by other conditions.

In the early stages of gastric cancer, the following symptoms may occur:

  • Indigestion and stomach discomfort.
  • A bloated feeling after eating.
  • Mild nausea.
  • Loss of appetite.
  • Heartburn.

In more advanced stages of gastric cancer, the following signs and symptoms may occur:

  • Blood in the stool.
  • Vomiting.
  • Weight loss for no known reason.
  • Stomach pain.
  • Jaundice (yellowing of eyes and skin).
  • Ascites (build-up of fluid in the abdomen).
  • Trouble swallowing.

Check with your doctor if you have any of these problems.

Tests that examine the stomach and esophagus are used to detect (find) and diagnose gastric cancer.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that produces it.
  • Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
    • The number of red blood cells, white blood cells, and platelets.
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
    • The portion of the sample made up of red blood cells.
     
  • Upper endoscopy: A procedure to look inside the esophagus, stomach, and duodenum (first part of the small intestine) to check for abnormal areas. An endoscope (a thin, lighted tube) is passed through the mouth and down the throat into the esophagus.
    Upper endoscopy; shows endoscope inserted through the mouth and esophagus and into the stomach. Inset shows patient on table having an upper endoscopy. 
    Upper endoscopy. A thin, lighted tube is inserted through the mouth to look for abnormal areas in the esophagus, stomach, and first part of the small intestine.
  • Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metalliccompound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.
    Barium swallow for stomach cancer; drawing shows barium liquid flowing through the esophagus and into the stomach. 
    Barium swallow for stomach cancer. The patient swallows barium liquid and it flows through the esophagus and into the stomach. X-rays are taken to look for abnormal areas.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer. A biopsy of the stomach is usually done during the endoscopy.

    One or more of the following tests may be done on the samples of tissue that are removed:

    • Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types of cancer.
    • FISH (fluorescence in situ hybridization): A laboratory technique used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light. The sample of blood or bone marrow is checked for HER2/neu to help decide the best treatment.
     

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The stage of the cancer (whether it is in the stomach only or has spread to lymph nodes or other places in the body).
  • The patient’s general health.

When gastric cancer is found very early, there is a better chance of recovery. Gastric cancer is often in an advanced stage when it is diagnosed. At later stages, gastric cancer can be treated but rarely can be cured. Taking part in one of the clinical trials being done to improve treatment should be considered. Information about ongoing clinical trials is available from the NCI Web site.

Stages of Gastric Cancer

After gastric cancer has been diagnosed, tests are done to find out if cancer cells have spread within the stomach or to other parts of the body.

The process used to find out if cancer has spread within the stomach or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.

The following tests and procedures may be used in the staging process:

  • CEA (carcinoembryonic antigen) assay: Tests that measure the level of CEA in the blood. This substance is released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, it can be a sign of gastric cancer or other conditions.
  • Endoscopic ultrasound (EUS): A procedure in which an endoscope is inserted into the body, usually through the mouth or rectum. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. A probe at the end of the endoscope is used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. This procedure is also called endosonography.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • PET scan (positron emission tomography scan): A procedure to find malignanttumor cells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. A PET scan and CT scan may be done at the same time. This is called a PET-CT.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if gastric cancer spreads to the liver, the cancer cells in the liver are actually gastric cancer cells. The disease is metastatic gastric cancer, not liver cancer.

The following stages are used for gastric cancer:

Stage 0 (Carcinoma in Situ)

In stage 0, abnormalcells are found in the inside lining of the mucosa (innermost layer) of the stomach wall. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I

In stage I, cancer has formed in the inside lining of the mucosa (innermost layer) of the stomach wall. Stage I is divided into stage IA and stage IB, depending on where the cancer has spread.

  • Stage IA: Cancer may have spread into the submucosa (layer of tissue next to the mucosa) of the stomach wall.
  • Stage IB: Cancer:
    • may have spread into the submucosa (layer of tissue next to the mucosa) of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
    • has spread to the muscle layer of the stomach wall.
     

Stage II

Stage II gastric cancer is divided into stage IIA and stage IIB, depending on where the cancer has spread.

  • Stage IIA: Cancer:
    • has spread to the subserosa (layer of tissue next to the serosa) of the stomach wall; or
    • has spread to the muscle layer of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
    • may have spread to the submucosa (layer of tissue next to the mucosa) of the stomach wall and is found in 3 to 6 lymph nodes near the tumor.
     
  • Stage IIB: Cancer:
    • has spread to the serosa (outermost layer) of the stomach wall; or
    • has spread to the subserosa (layer of tissue next to the serosa) of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
    • has spread to the muscle layer of the stomach wall and is found in 3 to 6 lymph nodes near the tumor; or
    • may have spread to the submucosa (layer of tissue next to the mucosa) of the stomach wall and is found in 7 or more lymph nodes near the tumor.
     

Stage III

Stage III gastric cancer is divided into stage IIIA, stage IIIB, and stage IIIC, depending on where the cancer has spread.

  • Stage IIIA: Cancer has spread to:
    • the serosa (outermost) layer of the stomach wall and is found in 1 or 2 lymph nodes near the tumor; or
    • the subserosa (layer of tissue next to the serosa) of the stomach wall and is found in 3 to 6 lymph nodes near the tumor; or
    • the muscle layer of the stomach wall and is found in 7 or more lymph nodes near the tumor.
     
  • Stage IIIB: Cancer has spread to:
    • nearby organs such as the spleen, transverse colon, liver, diaphragm, pancreas, kidney, adrenal gland, or small intestine, and may be found in 1 or 2 lymph nodes near the tumor; or
    • the serosa (outermost layer) of the stomach wall and is found in 3 to 6 lymph nodes near the tumor; or
    • the subserosa (layer of tissue next to the serosa) of the stomach wall and is found in 7 or more lymph nodes near the tumor.
     
  • Stage IIIC: Cancer has spread to:
    • nearby organs such as the spleen, transverse colon, liver, diaphragm, pancreas, kidney, adrenal gland, or small intestine, and may be found in 3 or more lymph nodes near the tumor; or
    • the serosa (outermost layer) of the stomach wall and is found in 7 or more lymph nodes near the tumor.
     

Stage IV

In stage IV, cancer has spread to distant parts of the body.

Recurrent Gastric Cancer

Recurrentgastriccancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the stomach or in other parts of the body such as the liver or lymph nodes.

Treatment Option Overview

There are different types of treatment for patients with gastric cancer.

Different types of treatments are available for patients with gastric cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

Surgery is a common treatment of all stages of gastric cancer. The following types of surgery may be used:

  • Subtotal gastrectomy: Removal of the part of the stomach that contains cancer, nearby lymph nodes, and parts of other tissues and organs near the tumor. The spleen may be removed. The spleen is an organ in the upper abdomen that filters the blood and removes old blood cells.
  • Total gastrectomy: Removal of the entire stomach, nearby lymph nodes, and parts of the esophagus, small intestine, and other tissues near the tumor. The spleen may be removed. The esophagus is connected to the small intestine so the patient can continue to eat and swallow.

If the tumor is blocking the stomach but the cancer cannot be completely removed by standard surgery, the following procedures may be used:

  • Endoluminal stent placement: A procedure to insert a stent (a thin, expandable tube) in order to keep a passage (such as arteries or the esophagus) open. For tumors blocking the passage into or out of the stomach, surgery may be done to place a stent from the esophagus to the stomach or from the stomach to the small intestine to allow the patient to eat normally.
  • Endoluminal laser therapy: A procedure in which an endoscope (a thin, lighted tube) with a laser attached is inserted into the body. A laser is an intense beam of light that can be used as a knife.
  • Gastrojejunostomy: Surgery to remove the part of the stomach with cancer that is blocking the opening into the small intestine. The stomach is connected to the jejunum (a part of the small intestine) to allow food and medicine to pass from the stomach into the small intestine.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Stomach (Gastric) Cancer for more information.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemoradiation

Chemoradiation therapy combines chemotherapy and radiation therapy to increase the effects of both. Chemoradiation given after surgery, to lower the risk that the cancer will come back, is called adjuvant therapy. Chemoradiation given before surgery, to shrink the tumor (neoadjuvant therapy), is being studied.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodytherapy is a type of targeted therapy used in the treatment of gastric cancer.

Monoclonal antibody therapy uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

See Drugs Approved for Stomach (Gastric) Cancer for more information.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Stage 0 (Carcinoma in Situ)

Treatment of stage 0 is usually surgery (total or subtotal gastrectomy).

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 gastric cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage I Gastric Cancer

Treatment of stage I gastric cancer may include the following:

  • Surgery (total or subtotal gastrectomy).
  • Surgery (total or subtotal gastrectomy) followed by chemoradiationtherapy.
  • A clinical trial of chemoradiation therapy given before surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I gastric cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage II Gastric Cancer

Treatment of stage II gastric cancer may include the following:

  • Surgery (total or subtotal gastrectomy).
  • Surgery (total or subtotal gastrectomy) followed by chemoradiationtherapy or chemotherapy.
  • Chemotherapy given before and after surgery.
  • A clinical trial of surgery followed by chemoradiation therapy testing new anticancer drugs.
  • A clinical trial of chemoradiation therapy given before surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II gastric cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage III Gastric Cancer

Treatment of stage III gastric cancer may include the following:

  • Surgery (total gastrectomy).
  • Surgery followed by chemoradiationtherapy or chemotherapy.
  • Chemotherapy given before and after surgery.
  • A clinical trial of surgery followed by chemoradiation therapy testing new anticancer drugs.
  • A clinical trial of chemoradiation therapy given before surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III gastric cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV and Recurrent Gastric Cancer

Treatment of stage IV or recurrentgastric cancer may include the following:

  • Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life.
  • Targeted therapy with a monoclonal antibody combined with chemotherapy.
  • Endoluminal laser therapy or endoluminal stent placement to relieve a blockage in the stomach, or gastrojejunostomy to bypass the blockage.
  • Radiation therapy as palliative therapy to stop bleeding, relieve pain, or shrink a tumor that is blocking the stomach.
  • Surgery as palliative therapy to stop bleeding or shrink a tumor that is blocking the stomach.
  • A clinical trial of new combinations of chemotherapy as palliative therapy to relieve symptoms and improve the quality of life.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV gastric cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Gastric Cancer

For more information from the National Cancer Institute about gastric cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on April 17, 2014.


General Information About Gastric Cancer

Incidence and Mortality

Estimated new cases and deaths from gastric cancer in the United States in 2014:[1]

  • New cases: 22,220.
  • Deaths: 10,990.

Epidemiology

Management of adenocarcinoma histology, which accounts for 90% to 95% of all gastric malignancies, is discussed in this summary. There are changing epidemiologic patterns in the United States regarding the anatomic location of esophagogastric cancers, with a trend of decreased occurrence of distal or noncardia gastric cancers.[2] However, in persons aged 25 to 39 years, there has been a significant increase in the incidence of noncardia gastric cancers from 0.27 cases per 100,000 individuals (1977–1981) to 0.45 cases per 100,000 individuals (2002–2006).[2] Additional studies are needed to confirm the observed increases in noncardia gastric cancers in this specific age group.

In contrast to the overall stable trend for noncardia gastric cancers, earlier studies demonstrated an increased incidence of adenocarcinomas of the gastric cardia of 4% to 10% per year from the mid-1970s to the late 1980s.[3] Similarly, the incidence of gastroesophageal junction adenocarcinomas increased sharply, from 1.22 cases per 100,000 individuals (1973–1978) to 2.00 cases per 100,000 individuals (1985–1990).[4] Since that time, incidence has remained steady, with an incidence of 1.94 cases per 100,000 individuals (2003–2008).[4] More recent data demonstrate that the incidence of gastric cardia cancers has been relatively stable, although an increase has been observed, from 2.4 cases per 100,000 individuals (1977–1981) to 2.9 cases per 100,000 individuals (2001–2006) in the Caucasian population.[2] The reasons for these temporal changes in incidence are unclear.

Risk Factors

In the United States, gastric cancer ranks 14th in incidence among the major types of cancer malignancies. While the precise etiology is unknown, acknowledged risk factors for gastric cancer include the following:[5][6][7]

  • Helicobacter pylori gastric infection.
  • Advanced age.
  • Male gender.
  • Diet low in fruits and vegetables.
  • Diet high in salted, smoked, or preserved foods.
  • Chronic atrophic gastritis.
  • Intestinal metaplasia.
  • Pernicious anemia.
  • Gastric adenomatous polyps.
  • Family history of gastric cancer.
  • Cigarette smoking.
  • Menetrier disease (giant hypertrophic gastritis).
  • Familial adenomatous polyposis.

Prognosis and Survival

The prognosis of patients with gastric cancer is related to tumor extent and includes both nodal involvement and direct tumor extension beyond the gastric wall.[8][9] Tumor grade may also provide some prognostic information.[10]

In localized distal gastric cancer, more than 50% of patients can be cured. However, early-stage disease accounts for only 10% to 20% of all cases diagnosed in the United States. The remaining patients present with metastatic disease in either regional or distant sites. The overall survival rate in these patients at 5 years ranges from almost no survival for patients with disseminated disease to almost 50% survival for patients with localized distal gastric cancers confined to resectable regional disease. Even with apparent localized disease, the 5-year survival rate of patients with proximal gastric cancer is only 10% to 15%. Although the treatment of patients with disseminated gastric cancer may result in palliation of symptoms and some prolongation of survival, long remissions are uncommon.

Gastrointestinal stromal tumors occur most commonly in the stomach. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.)

Related Summaries

Other PDQ summaries containing information related to gastric cancer include the following:

  • Stomach (Gastric) Cancer Prevention.
  • Stomach (Gastric) Cancer Screening.
  • Unusual Cancers of Childhood (childhood cancer of the stomach).

References:

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.

  2. Anderson WF, Camargo MC, Fraumeni JF Jr, et al.: Age-specific trends in incidence of noncardia gastric cancer in US adults. JAMA 303 (17): 1723-8, 2010.

  3. Blot WJ, Devesa SS, Kneller RW, et al.: Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265 (10): 1287-9, 1991.

  4. Buas MF, Vaughan TL: Epidemiology and risk factors for gastroesophageal junction tumors: understanding the rising incidence of this disease. Semin Radiat Oncol 23 (1): 3-9, 2013.

  5. Kurtz RC, Sherlock P: The diagnosis of gastric cancer. Semin Oncol 12 (1): 11-8, 1985.

  6. Scheiman JM, Cutler AF: Helicobacter pylori and gastric cancer. Am J Med 106 (2): 222-6, 1999.

  7. Fenoglio-Preiser CM, Noffsinger AE, Belli J, et al.: Pathologic and phenotypic features of gastric cancer. Semin Oncol 23 (3): 292-306, 1996.

  8. Siewert JR, Böttcher K, Stein HJ, et al.: Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg 228 (4): 449-61, 1998.

  9. Nakamura K, Ueyama T, Yao T, et al.: Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy. Cancer 70 (5): 1030-7, 1992.

  10. Adachi Y, Yasuda K, Inomata M, et al.: Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type. Cancer 89 (7): 1418-24, 2000.

Cellular Classification of Gastric Cancer

There are two major types of gastric adenocarcinoma including the following:

  • Intestinal.
  • Diffuse.

Intestinal adenocarcinomas are well differentiated, and the cells tend to arrange themselves in tubular or glandular structures. The terms tubular, papillary, and mucinous are assigned to the various types of intestinal adenocarcinomas. Rarely, adenosquamous cancers can occur.

Diffuse adenocarcinomas are undifferentiated or poorly differentiated, and they lack a gland formation. Clinically, diffuse adenocarcinomas can give rise to infiltration of the gastric wall (i.e., linitis plastica).

Some tumors can have mixed features of intestinal and diffuse types.

Stage Information for Gastric Cancer

Definitions of TNM

The American Joint Committee on Cancer has designated staging by TNM classification to define gastric cancer.[1][2][3]

Table 1. Primary Tumor (T)a

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

Tis

Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria.

T1

Tumor invades lamina propria, muscularis mucosae, or submucosa.

T1a

Tumor invades lamina propria or muscularis mucosae.

T1b

Tumor invades submucosa.

T2

Tumor invades muscularis propria.b

T3

Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures.c,d

T4

Tumor invades serosa (visceral peritoneum) or adjacent structures.c,d

T4a

Tumor invades serosa (visceral peritoneum).

T4b

Tumor invades adjacent structures.

aReprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.

bA tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified T3. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified T4.

cThe adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum.

dIntramural extension to the duodenum or esophagus is classified by the depth of the greatest invasion in any of these sites, including the stomach.

Table 2. Regional Lymph Nodes (N)a

NX

Regional lymph node(s) cannot be assessed.

N0

No regional lymph node metastasis.b

N1

Metastases in 1–2 regional lymph nodes.

N2

Metastases in 3–6 regional lymph nodes.

N3

Metastases in ≥7 regional lymph nodes.

N3a

Metastases in 7–15 regional lymph nodes.

N3b

Metastases in ≥16 regional lymph nodes.

aReprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.

bA designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.

Table 3. Distant Metastasisa

M0

No distant metastasis.

M1

Distant metastasis.

aReprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage

T

N

M

0

Tis

N0

M0

IA

T1

N0

M0

IB

T2

N0

M0

T1

N1

M0

IIA

T3

N0

M0

T2

N1

M0

T1

N2

M0

IIB

T4a

N0

M0

T3

N1

M0

T2

N2

M0

T1

N3

M0

IIIA

T4a

N1

M0

T3

N2

M0

T2

N3

M0

IIIB

T4b

N0

M0

T4b

N1

M0

T4a

N2

M0

T3

N3

M0

IIIC

T4b

N2

M0

T4b

N3

M0

T4a

N3

M0

IV

Any T

Any N

M1

aReprinted with permission from AJCC: Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 117-26.

References:

  1. Stomach. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, p 120.

  2. Roder JD, Böttcher K, Busch R, et al.: Classification of regional lymph node metastasis from gastric carcinoma. German Gastric Cancer Study Group. Cancer 82 (4): 621-31, 1998.

  3. Ichikura T, Tomimatsu S, Uefuji K, et al.: Evaluation of the New American Joint Committee on Cancer/International Union against cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification. Cancer 86 (4): 553-8, 1999.

Treatment Option Overview

Radical surgery represents the standard form of therapy that has curative intent. However, the incidences of local failure in the tumor bed and regional lymph nodes, and distant failures via hematogenous or peritoneal routes, remain high.[1] As such, adjuvant external-beam radiation therapy with combined chemotherapy has been evaluated in the United States.

In a phase III Intergroup trial (SWOG-9008), 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction were randomly assigned to receive surgery alone or surgery plus postoperative chemotherapy (5-fluorouracil [5-FU] and leucovorin) and concurrent radiation therapy (45 Gy). With 5 years' median follow-up, a significant survival benefit was reported for patients who received adjuvant combined modality therapy.[2][Level of evidence: 1iiA] Median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) rates and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005). The rate of distant metastases was 18% for the surgery-alone arm and 33% for the chemoradiation-therapy arm. Because distant disease remains a significant concern, the aim of the Cancer and Leukemia Group B study (CALGB-80101) was to augment the postoperative chemoradiation regimen used in INT-0116. Neoadjuvant chemoradiation therapy such as in the RTOG-9904 trial, which is now completed, and the SWOG-S0425 (NCT00335959) trial, which is now closed, was clinically evaluated.[3]

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[4] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-FU before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[4][Level of evidence: 1iiA]

References:

  1. Gunderson LL, Sosin H: Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 8 (1): 1-11, 1982.

  2. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.

  3. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.

  4. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.

Stage 0 Gastric Cancer

Standard treatment options:

  • Surgery.

Stage 0 is gastric cancer confined to mucosa. Experience in Japan, where stage 0 is diagnosed frequently, indicates that more than 90% of patients treated by gastrectomy with lymphadenectomy will survive beyond 5 years. An American series has confirmed these results.[1]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 gastric cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Green PH, O'Toole KM, Slonim D, et al.: Increasing incidence and excellent survival of patients with early gastric cancer: experience in a United States medical center. Am J Med 85 (5): 658-61, 1988.

Stage I Gastric Cancer

Standard treatment options:

  1. One of the following surgical procedures:
    • Distal subtotal gastrectomy (if the lesion is not in the fundus or at the cardioesophageal junction).
    • Proximal subtotal gastrectomy or total gastrectomy, both with distal esophagectomy (if the lesion involves the cardia). These tumors often involve the submucosal lymphatics of the esophagus.
    • Total gastrectomy (if the tumor involves the stomach diffusely or arises in the body of the stomach and extends to within 6 cm of the cardia or distal antrum).

    Regional lymphadenectomy is recommended with all of the above procedures. Splenectomy is not routinely performed.[1]

  2. Postoperative chemoradiation therapy for patients with node-positive (T1 N1) and muscle-invasive (T2 N0) disease.[2]

Surgical resection including regional lymphadenectomy is the treatment of choice for patients with stage I gastric cancer.[1] If the lesion is not in the cardioesophageal junction and does not diffusely involve the stomach, subtotal gastrectomy is the procedure of choice, since it has been demonstrated to provide equivalent survival when compared with total gastrectomy and is associated with decreased morbidity.[3][Level of evidence: 1iiA] When the lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy (including a sufficient length of esophagus) may be performed with curative intent. If the lesion diffusely involves the stomach, total gastrectomy is required. At a minimum, surgical resection should include greater and lesser curvature perigastric regional lymph nodes. Note that in patients with stage I gastric cancer, perigastric lymph nodes may contain cancer.

In patients with node-positive (T1 N1) and muscle-invasive (T2 N0) disease, postoperative chemoradiation therapy may be considered. A prospective multi-institution phase III trial (SWOG-9008) evaluated postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction and reported a significant survival benefit with adjuvant combined modality therapy.[2][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) rates and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005). However, only 36 patients in the trial had stage IB tumors (18 patients in each arm).[4] Since the prognosis is relatively favorable for patients with completely resected stage IB disease, the effectiveness of adjuvant chemoradiation therapy for this group is less clear.

Treatment options under clinical evaluation:

  • Neoadjuvant chemoradiation therapy such as in the SWOG-S0425, which is now closed, and the RTOG-9904 trial, which is now completed.[5]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I gastric cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996.

  2. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.

  3. Bozzetti F, Marubini E, Bonfanti G, et al.: Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Ann Surg 230 (2): 170-8, 1999.

  4. Kelsen DP: Postoperative adjuvant chemoradiation therapy for patients with resected gastric cancer: intergroup 116. J Clin Oncol 18 (21 Suppl): 32S-4S, 2000.

  5. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.

Stage II Gastric Cancer

Standard treatment options:

  1. One of the following surgical procedures:
    • Distal subtotal gastrectomy (if the lesion is not in the fundus or at the cardioesophageal junction).
    • Proximal subtotal gastrectomy or total gastrectomy (if the lesion involves the cardia).
    • Total gastrectomy (if the tumor involves the stomach diffusely or arises in the body of the stomach and extends to within 6 cm of the cardia).

    Regional lymphadenectomy is recommended with all of the above procedures. Splenectomy is not routinely performed.[1]

  2. Postoperative chemoradiation therapy.[2]
  3. Perioperative chemotherapy.[3]
  4. Postoperative chemotherapy.

Surgical resection with regional lymphadenectomy is the treatment of choice for patients with stage II gastric cancer.[1] If the lesion is not in the cardioesophageal junction and does not diffusely involve the stomach, subtotal gastrectomy is the procedure of choice. When the lesion involves the cardia, proximal subtotal gastrectomy or total gastrectomy may be performed with curative intent. If the lesion diffusely involves the stomach, total gastrectomy and appropriate lymph node resection may be required. The role of extended lymph node (D2) dissection is uncertain [4] and in some series is associated with increased morbidity.[5][6]

Postoperative chemoradiation therapy may be considered for patients with stage II gastric cancer. A prospective multi-institution phase III trial (SWOG-9008) evaluated postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction and reported a significant survival benefit with adjuvant combined modality therapy.[2][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005).The rate of distant metastases was 32% for the surgery-alone arm and 40% for the chemoradiation therapy arm. Because distant disease remains a significant concern, the aim of the Cancer and Leukemia Group B study (CALGB-80101), which is now closed, was to augment the postoperative chemoradiation regimen used in SWOG-9008.[7] Neoadjuvant chemoradiation therapy remains under clinical evaluation, such as in the SWOG-S0425 (NCT00335959) trial, which is now closed and the RTOG-9904 trial, which is now completed.[8]

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[3] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion fluorouracil (ECF) before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%, 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%, 95% CI, 16.6 to 29.4 for the surgery group.[3][Level of evidence: 1iiA]

Japanese investigators randomly assigned 1,059 patients with stage II or III gastric cancer who had undergone a D2 gastrectomy to receive either 1 year of S-1, an oral fluoropyrimidine not available in the United States, or follow-up after surgery alone.[9] Patients were randomly assigned in a 1:1 fashion. The 3-year OS rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The HR for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% CI, 0.52–0.87; P = .003).[9][Level of evidence: 1iiA]

Subsequently, investigators in Asia evaluated the role of capecitabine/oxaliplatin as adjuvant therapy after gastric cancer resection. In the CLASSIC (NCT00411229) trial , 37 centers in South Korea, China, and Taiwan randomly assigned 1,035 patients with stage IIA, IIB, IIIA, or IIIB gastric cancer who had undergone a curative D2 gastrectomy to receive adjuvant chemotherapy (eight 3-week cycles of capecitabine plus oxaliplatin) or follow-up post-surgery alone.[10] The 3-year disease-free survival rate was 74% in the chemotherapy group and 59% in the surgery-alone group (HR, 0.56; 95% CI, 0.44–0.72; P < .0001). The 3-year OS was 83% in the chemotherapy group and 78% in the surgery-alone group (HR, 0.72; 95% CI, 0.52–1.00; P = .0493).[10][Level of evidence: 1iiA] Further follow-up is anticipated.

Treatment options under clinical evaluation:

  1. Postoperative chemoradiation therapy with ECF as evidenced in the CALGB-80101 trial, which is now closed.[7]
  2. Neoadjuvant chemoradiation therapy as evidenced in the SWOG-S0425 trial, which is now closed, and the RTOG-9904 trial, which is now completed.[8]

All newly diagnosed patients with stage II gastric cancer should be considered candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II gastric cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996.

  2. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.

  3. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.

  4. Kitamura K, Yamaguchi T, Sawai K, et al.: Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients. J Clin Oncol 15 (12): 3471-80, 1997.

  5. Bonenkamp JJ, Songun I, Hermans J, et al.: Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 345 (8952): 745-8, 1995.

  6. Cuschieri A, Fayers P, Fielding J, et al.: Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial.The Surgical Cooperative Group. Lancet 347 (9007): 995-9, 1996.

  7. Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.

  8. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.

  9. Sakuramoto S, Sasako M, Yamaguchi T, et al.: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357 (18): 1810-20, 2007.

  10. Bang YJ, Kim YW, Yang HK, et al.: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379 (9813): 315-21, 2012.

Stage III Gastric Cancer

Standard treatment options:

  1. Radical surgery. Curative resection procedures are confined to patients who do not have extensive nodal involvement at the time of surgical exploration.
  2. Postoperative chemoradiation therapy.[1]
  3. Perioperative chemotherapy.[2]
  4. Postoperative chemotherapy.

All patients with tumors that can be resected should undergo surgery. As many as 15% of selected stage III patients can be cured by surgery alone, particularly if lymph node involvement is minimal (<7 lymph nodes).

Postoperative chemoradiation therapy may be considered for patients with stage III gastric cancer. A prospective multi-institution phase III trial (SWOG-9008) evaluating postoperative combined chemoradiation therapy versus surgery alone in 556 patients with completely resected stage IB to stage IV (M0) adenocarcinoma of the stomach and gastroesophageal junction reported a significant survival benefit with adjuvant combined modality therapy.[1][Level of evidence: 1iiA] With a median follow-up of 5 years, median survival was 36 months for the adjuvant chemoradiation therapy group as compared to 27 months for the surgery-alone arm (P = .005). Three-year overall survival (OS) and relapse-free survival rates were 50% and 48%, respectively, with adjuvant chemoradiation therapy versus 41% and 31%, respectively, for surgery alone (P = .005). Because distant disease remains a significant concern, the aim of the Cancer and Leukemia Group B study (CALGB-80101), which is now closed, was to augment the postoperative chemoradiation regimen used in the SWOG-9008 trial, for example, and the preoperative chemotherapy and chemoradiation therapy regimen used, for example, in the RTOG-9904 trial, which is now completed.

Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy.[2] In the randomized phase III trial (MRC-ST02), patients with stage II or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-fluorouracil (ECF) before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival (hazard ratio [HR] for progression, 0.66; 95% confidence interval [CI], 0.53–0.81; P < .001) and of OS (HR for death, 0.75; 95% CI, 0.60–0.93; P = .009). Five-year OS was 36.3%; 95% CI, 29 to 43 for the perioperative chemotherapy group and 23%; 95% CI, 16.6 to 29.4 for the surgery group.[2][Level of evidence: 1iiA]

Japanese investigators randomly assigned 1,059 patients with stage II or III gastric cancer who had undergone a D2 gastrectomy to receive either 1 year of S-1, an oral fluoropyrimidine not available in the United States, or follow-up after surgery alone.[3] Patients were randomized in a 1:1 fashion. The 3-year OS rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The HR for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% CI, 0.52–0.87; P = .003).[3][Level of evidence: 1iiA]

Subsequently, investigators in Asia evaluated the role of capecitabine/oxaliplatin as adjuvant therapy after gastric cancer resection. In the CLASSIC (NCT00411229) trial , 37 centers in South Korea, China, and Taiwan randomly assigned 1,035 patients with stage IIA, IIB, IIIA, or IIIB gastric cancer who had undergone a curative D2 gastrectomy to receive adjuvant chemotherapy (eight 3-week cycles of capecitabine plus oxaliplatin) or follow-up post-surgery alone.[4] The 3-year disease-free survival rate was 74% in the chemotherapy group and 59% in the surgery-alone group (HR, 0.56; 95% CI, 0.44–0.72; P < .0001). The 3-year OS was 83% in the chemotherapy group and 78% in the surgery-alone group (HR, 0.72; 95% CI, 0.52–1.00; P = .0493).[4][Level of evidence: 1iiA] Further follow-up is anticipated.

Treatment options under clinical evaluation:

  1. Postoperative chemoradiation with ECF such as in the CALGB-80101 trial, which is now closed.[5]
  2. Neoadjuvant chemoradiation therapy has been under clinical evaluation, such as in the SWOG-S0425 (NCT00335959) trial, which is now closed, and the RTOG-9904 trial, which is now completed.[6]

All newly diagnosed patients with stage III gastric cancer should be considered candidates for clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III gastric cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.

  2. Cunningham D, Allum WH, Stenning SP, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355 (1): 11-20, 2006.

  3. Sakuramoto S, Sasako M, Yamaguchi T, et al.: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357 (18): 1810-20, 2007.

  4. Bang YJ, Kim YW, Yang HK, et al.: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379 (9813): 315-21, 2012.

  5. Fuchs C, Tepper JE, Niedwiecki D, et al.: Postoperative adjuvant chemoradiation for gastric or gastroesophageal adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (RT): interim toxicity results from Intergroup trial CALGB 80101. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-61, 2006.

  6. Ajani JA, Winter K, Okawara GS, et al.: Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol 24 (24): 3953-8, 2006.

Stage IV and Recurrent Gastric Cancer

Standard treatment options:

  1. Palliative chemotherapy with:
    • Fluorouracil (5-FU).[1][2][3]
    • Epirubicin, cisplatin, and 5-FU (ECF).[4][5]
    • Epirubicin, oxaliplatin, and capecitabine (EOX).[6]
    • Cisplatin and 5-FU (CF).[7][3]
    • Docetaxel, cisplatin, and 5-FU.[8]
    • Etoposide, leucovorin, and 5-FU (ELF).[9]
    • 5-FU, doxorubicin, and methotrexate (FAMTX).[7]
  2. Trastuzumab, cisplatin, and either 5-FU or capecitabine in patients with HER2-positive tumors (3+ on immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]-positive).
  3. Endoluminal laser therapy, endoluminal stent placement, or gastrojejunostomy, may be helpful to patients with gastric obstruction.[10]
  4. Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
  5. Palliative resection should be reserved for patients with continued bleeding or obstruction.

Standard chemotherapy versus best supportive care for patients with metastatic gastric cancer has been tested in several clinical trials, and there is general agreement that patients who receive chemotherapy live for several months longer on average than patients who receive supportive care.[11][12][13][Level of evidence: 1iiA] During the last 20 years, multiple randomized studies evaluating different treatment regimens (monotherapy vs. combination chemotherapy) have been performed in patients with metastatic gastric cancer with no clear consensus emerging as to the best management approach. A meta-analysis of these studies demonstrated an hazard ratio (HR) of 0.83 for overall survival (OS) (95% confidence interval [CI], 0.74–0.93) in favor of combination chemotherapy.[14]

Of all the combination regimens, ECF is often considered the reference standard in the United States and Europe. In one European trial, 274 patients with metastatic esophagogastric cancer were randomly assigned to receive either ECF or FAMTX.[15] The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[15][Level of evidence: 1iiA] In a second trial that compared ECF with mitomycin, cisplatin, and 5-FU (MCF), there was no statistically significant difference in median survival (9.4 vs. 8.7 months, P = .315).[5][Level of evidence: 1iiA]

Oxaliplatin and capecitabine are often substituted for cisplatin and 5-FU within the ECF regimen as a result of data from the REAL-2 trial ( ISRCTN51678883).[6] This randomized trial of 1,002 patients with advanced esophageal, gastroesophageal (GE) junction, or gastric cancer utilized a 2 × 2 design to demonstrate noninferior median OS in patients treated with capecitabine rather than 5-FU (HRdeath = 0.86; 95% CI, 0.82–0.99) and in patients treated with oxaliplatin in place of cisplatin (HRdeath = 0.92; 95% CI, 0.80–1.10).

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF.[16] Time-to-treatment progression (TTP) was the primary endpoint. Patients who received DCF experienced a significantly longer TTP (5.6 months; 95% CI, 4.9–5.9; vs. 3.7 months; 95% CI, 3.4–4.5; HR, 1.47; 95% CI, 1.19–1.82; log-rank P < .001; risk reduction 32%). The median OS was significantly longer for patients who received DCF versus patients who received CF (9.2 months; 95% CI, 8.4–10.6; vs. 8.6 months; 95% CI, 7.2–9.5; HR, 1.29; 95% CI, 1.0–1.6; log-rank P = .02; risk reduction = 23%).[16][Level of evidence: 1iiA] There were high toxicity rates in both arms.[17] Febrile neutropenia was more common in patients who received DCF (29% vs. 12%), and the death rate on the study was 10.4% for patients on the DCF arm and 9.4% for patients on the CF arm.

Whether the CF regimen should be considered as an index regimen for the treatment of patients with metastatic gastric cancer is the subject of debate.[17] The results of a study that randomly assigned 245 patients with metastatic gastric cancer to receive CF, FAMTX, or ELF demonstrated no significant difference in response rate, progression-free survival, or OS between the arms.[7] Grades 3 and 4 neutropenia occurred in 35% to 43% of patients on all arms, but severe nausea and vomiting was more common in patients in the CF arm and occurred in 26% of those patients.[7][Level of evidence: 1iiDiv]

In an open-label, international phase III trial, patients with HER2-positive metastatic, inoperable locally advanced, or recurrent gastric or GE junction cancer were randomly assigned to chemotherapy with or without the anti-HER2 monoclonal antibody trastuzumab.[18] HER2 positivity was defined as either 3+ staining by IHC or a HER2 to CEP17 ratio of two or more using FISH. Tumors from 3,665 patients were HER2 tested; of the patients, 810 were positive (22%) and 594 met eligibility criteria for randomization. Chemotherapy consisted of cisplatin plus 5-FU or capecitabine chosen at the investigator’s discretion. The study treatment was administered every 3 weeks for six cycles, and trastuzumab was continued every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Crossover to trastuzumab at disease progression was not permitted. Median OS was 13.8 months (95% CI, 12–16) in patients assigned to trastuzumab and 11.1 months (95% CI, 10–13) in patients assigned to chemotherapy alone (HR, 0.74; 95% CI, 0.60–0.91; P = .0046).[18][Level of evidence: 1iiA] There was no significant difference in rates of any adverse event, and cardio toxic effects were equally rare in both arms.

When patients develop progression of disease after first-line chemotherapy, there is no standard treatment option. Investigators in Korea randomly assigned patients with advanced gastric cancer who had received one or two prior chemotherapy regimens involving both a fluoropyrimidine and a platinum agent to either salvage chemotherapy or best supportive care in a 2:1 fashion.[19] Salvage chemotherapy consisted of either docetaxel (60 mg/m2 every 3 weeks) or irinotecan (150 mg/m2 every 2 weeks) and was left to the discretion of the treating physicians. Of the 202 patients enrolled, 133 received salvage chemotherapy and 69 received best supportive care. Median OS was 5.3 months in the group that received salvage chemotherapy and 3.8 months in the group that received best supportive care (HR, 0.657; P = .007). There was no difference in median OS between docetaxel and irinotecan (5.2 months vs. 6.5 months, P = .116).[19][Level of evidence: 1iiA]

Treatment options under clinical evaluation:

  • Palliative chemotherapy with:
    • Irinotecan and cisplatin.
    • Folic acid, 5-FU, and irinotecan (FOLFIRI).
    • Leucovorin, 5-FU, and oxaliplatin (FOLFOX).

Phase II studies evaluating irinotecan-based or oxaliplatin-based regimens demonstrate similar response rates and TTP to those found with ECF or CF, but the former may be less toxic.[20][21][22][23][24][25] There are conflicting data regarding relative efficacy of any one regimen for another. Ongoing studies are evaluating these newer regimens.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV gastric cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

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  2. Cullinan SA, Moertel CG, Fleming TR, et al.: A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA 253 (14): 2061-7, 1985.

  3. Ohtsu A, Shimada Y, Shirao K, et al.: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21 (1): 54-9, 2003.

  4. Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.

  5. Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.

  6. Cunningham D, Starling N, Rao S, et al.: Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358 (1): 36-46, 2008.

  7. Vanhoefer U, Rougier P, Wilke H, et al.: Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18 (14): 2648-57, 2000.

  8. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al.: Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24 (31): 4991-7, 2006.

  9. Ajani JA, Ota DM, Jackson DE: Current strategies in the management of locoregional and metastatic gastric carcinoma. Cancer 67 (1 Suppl): 260-5, 1991.

  10. Ell C, Hochberger J, May A, et al.: Coated and uncoated self-expanding metal stents for malignant stenosis in the upper GI tract: preliminary clinical experiences with Wallstents. Am J Gastroenterol 89 (9): 1496-500, 1994.

  11. Murad AM, Santiago FF, Petroianu A, et al.: Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72 (1): 37-41, 1993.

  12. Pyrhönen S, Kuitunen T, Nyandoto P, et al.: Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71 (3): 587-91, 1995.

  13. Glimelius B, Ekström K, Hoffman K, et al.: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8 (2): 163-8, 1997.

  14. Wagner AD, Grothe W, Haerting J, et al.: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24 (18): 2903-9, 2006.

  15. Webb A, Cunningham D, Scarffe JH, et al.: Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15 (1): 261-7, 1997.

  16. Ajani JA, Moiseyenko VM, Tjulandin S, et al.: Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25 (22): 3205-9, 2007.

  17. Ilson DH: Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol 25 (22): 3188-90, 2007.

  18. Bang YJ, Van Cutsem E, Feyereislova A, et al.: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376 (9742): 687-97, 2010.

  19. Kang JH, Lee SI, Lim do H, et al.: Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30 (13): 1513-8, 2012.

  20. Ilson DH, Saltz L, Enzinger P, et al.: Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 17 (10): 3270-5, 1999.

  21. Beretta E, Di Bartolomeo M, Buzzoni R, et al.: Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition. Tumori 92 (5): 379-83, 2006 Sep-Oct.

  22. Pozzo C, Barone C, Szanto J, et al.: Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 15 (12): 1773-81, 2004.

  23. Bouché O, Raoul JL, Bonnetain F, et al.: Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol 22 (21): 4319-28, 2004.

  24. Ajani JA, Baker J, Pisters PW, et al.: CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma: results of a phase II study. Cancer 94 (3): 641-6, 2002.

  25. Cavanna L, Artioli F, Codignola C, et al.: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 29 (4): 371-5, 2006.


This information is provided by the National Cancer Institute.

This information was last updated on July 31, 2014.


 
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