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.
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| 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 Adult Soft Tissue Sarcoma 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. People who think they may be at risk should discuss this with their doctor. 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.
Possible signs of gastric cancer include indigestion and stomach discomfort or pain.
These and other symptoms may be caused by gastric cancer. Other conditions may cause the same symptoms.
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 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.
A doctor should be consulted if any of these problems occur.
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.
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| 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. |
- Fecal occult blood test: A test to check stool (solid waste) for blood that can only be seen with a microscope. Small samples of stool are placed on special cards and returned to the doctor or laboratory for testing.
- Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metallic compound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.
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| Barium swallow. The patient swallows barium liquid and it flows through the esophagus and into the stomach. X-rays are taken to look for abnormal areas. |
- 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.
- 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.
Certain factors affect prognosis (chance of recovery) and treatment options.
The prognosis (chance of recovery) and treatment options depend on the following:
- The stage and extent 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.
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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:
- β-hCG (beta-human chorionic gonadotropin), CA-125, and CEA (carcinoembryonic antigen) assays: Tests that measure the levels of β-hCG, CA-125, and CEA in the blood. These substances are released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, they can be a sign of gastric cancer or other conditions.
- Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
- 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.
- Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy.
- 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.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
- Through tissue. Cancer invades the surrounding normal tissue.
- Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
- Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone 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 mucosal (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. Stage I is divided into stage IA and stage IB, depending on where the cancer has spread.
- Stage IA: Cancer has spread completely through the mucosal (innermost) layer of the stomach wall.
- Stage IB: Cancer has spread:
- completely through the mucosal (innermost) layer of the stomach wall and is found in up to 6 lymph nodes near the tumor; or
- to the muscularis (middle) layer of the stomach wall.
Stage II
In stage II gastric cancer, cancer has spread:
- completely through the mucosal (innermost) layer of the stomach wall and is found in 7 to 15 lymph nodes near the tumor; or
- to the muscularis (middle) layer of the stomach wall and is found in up to 6 lymph nodes near the tumor; or
- to the serosal (outermost) layer of the stomach wall but not to lymph nodes or other organs.
Stage III
Stage III gastric cancer is divided into stage IIIA and stage IIIB depending on where the cancer has spread.
- Stage IIIA: Cancer has spread to:
- the muscularis (middle) layer of the stomach wall and is found in 7 to 15 lymph nodes near the tumor; or
- the serosal (outermost) layer of the stomach wall and is found in 1 to 6 lymph nodes near the tumor; or
- organs next to the stomach but not to lymph nodes or other parts of the body.
- Stage IIIB: Cancer has spread to the serosal (outermost) layer of the stomach wall and is found in 7 to 15 lymph nodes near the tumor.
Stage IV
In stage IV, cancer has spread to:
- organs next to the stomach and to at least one lymph node; or
- more than 15 lymph nodes; or
- other parts of the body.
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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.
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Treatment Option Overview
There are different types of treatment for patients with gastric cancer.
Different types of treatments are available for patients with gastriccancer. 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.
Four 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.
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 spinal column, 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.
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 combines chemotherapy and radiation therapy to increase the effects of both. Chemoradiation treatment given after surgery to increase the chances of a cure is called adjuvant therapy. If it is given before surgery, it is called neoadjuvant therapy.
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 clinical trials database.
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.
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Treatment Options by Stage
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
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 PDQ Cancer Clinical Trials Registry 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. 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 chemoradiation therapy.
- A clinical trial of chemoradiation therapy given before surgery.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. 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 chemoradiation therapy.
- 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 PDQ Cancer Clinical Trials Registry 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. 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 chemoradiation therapy.
- 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 PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.
Stage IV Gastric Cancer
Treatment of stage IV gastric cancer that has not spread to distant organs may include the following:
- Surgery (total gastrectomy).
- Surgery followed by chemoradiation therapy.
- 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.
Treatment of stage IV gastric cancer that has spread to distant organs may include the following:
- Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life.
- Endoluminal laser therapy or endoluminal stent placement to relieve a blockage in the stomach.
- 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 PDQ Cancer Clinical Trials Registry 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. General information about clinical trials is available from the NCI Web site.
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Treatment Options for Recurrent Gastric Cancer
Treatment of recurrentgastriccancer may include the following:
- Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life.
- Endoluminal laser therapy or endoluminal stent placement to relieve a blockage in the stomach.
- 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 PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent 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. General information about clinical trials is available from the NCI Web site.
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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:
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This information is provided by the National Cancer Institute.
This information was last updated on May 6, 2008.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gastric cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Risk factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
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General Information About Gastric Cancer
Related Summaries
Other PDQ summaries containing information related to gastric cancer include:
- Unusual Cancers of Childhood.
- Gastric Cancer Prevention.
- Gastric Cancer Screening.
Statistics
Estimated new cases and deaths from gastric cancer in the United States in 2009:[1]
- New cases: 21,130.
- Deaths: 10,620.
Epidemiology
Management of adenocarcinoma histology, which accounts for 90% to 95% of all gastric malignancies,
is discussed in this summary. The site
of cancer origin within the stomach has changed in frequency in the United
States over recent decades.[2] Cancer of the distal half of the stomach has
been decreasing in the United States since the 1930s. However, in the last 2
decades, the incidence of cancer of the cardia and gastroesophageal junction
has been rapidly rising. The incidence of this cancer has increased
dramatically, especially in patients younger than 40 years.
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:[3][4][5]
- 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
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.[6][7] Tumor grade may also provide some prognostic information.[8]
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 Adult Soft Tissue Sarcoma Treatment for more information.)
References:
American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online. Last accessed January 6, 2010.
Blot WJ, Devesa SS, Kneller RW, et al.: Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265 (10): 1287-9, 1991.
Kurtz RC, Sherlock P: The diagnosis of gastric cancer. Semin Oncol 12 (1): 11-8, 1985.
Scheiman JM, Cutler AF: Helicobacter pylori and gastric cancer. Am J Med 106 (2): 222-6, 1999.
Fenoglio-Preiser CM, Noffsinger AE, Belli J, et al.: Pathologic and phenotypic features of gastric cancer. Semin Oncol 23 (3): 292-306, 1996.
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.
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.
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.
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Cellular Classification of Gastric Cancer
There are two major types of gastric adenocarcinoma:
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.
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Stage Information for Gastric Cancer
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification.[1][2][3]
TNM Definitions
Primary tumor (T)
- 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 or submucosa
- T2: Tumor invades the muscularis propria or the subserosa*
- T2a: Tumor invades muscularis propria
- T2b: Tumor invades subserosa
- T3: Tumor penetrates the serosa (visceral peritoneum) without invading
adjacent structures**,***
- T4: Tumor invades adjacent structures**,***
*A 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 T2. If there is perforation of the
visceral peritoneum covering the gastric ligaments or the omentum, the tumor
should be classified T3.
**The adjacent structures of the stomach include the spleen, transverse
colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney,
small intestine, and retroperitoneum.
***Intramural extension to the duodenum or esophagus is classified by
the depth of greatest invasion in any of these sites, including stomach.
Regional lymph nodes (N)
The regional lymph nodes are the perigastric nodes, found along the lesser and
greater curvatures, and the nodes located along the left gastric, common
hepatic, splenic, and celiac arteries. For pN, a regional lymphadenectomy
specimen will ordinarily contain at least 15 lymph nodes. Involvement of other
intra-abdominal lymph nodes, such as the hepatoduodenal, retropancreatic,
mesenteric, and para-aortic, is classified as distant metastasis.
- NX: Regional lymph node(s) cannot be assessed
- N0: No regional lymph node metastasis*
- N1: Metastasis in one to six regional lymph nodes
- N2: Metastasis in 7 to 15 regional lymph nodes
- N3: Metastasis in more than 15 regional lymph nodes
*A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined.
Distant metastasis (M)
- MX: Distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
AJCC Stage Groupings
Stage 0
Stage IA
Stage IB
- T1, N1, M0
- T2a, N0, M0
- T2b, N0, M0
Stage II
- T1, N2, M0
- T2a, N1, M0
- T2b, N1, M0
- T3, N0, M0
Stage IIIA
- T2a, N2, M0
- T2b, N2, M0
- T3, N1, M0
- T4, N0, M0
Stage IIIB
Stage IV
- T4, N1, M0
- T4, N2, M0
- T4, N3, M0
- T1, N3, M0
- T2, N3, M0
- T3, N3, M0
- Any T, any N, M1
References:
Stomach. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 99-106.
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.
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.
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Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
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 (INT-0116),
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 32% for the surgery-alone arm and 40% for the chemoradiation therapy arm. Because distant disease remains a significant concern, the aim of the current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in INT-0116. Neoadjuvant
chemoradiation therapy such as in the RTOG-9904 trial also remains under clinical evaluation in the SWOG-S0425 trial.[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:
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.
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.
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.
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.
Top
Stage 0 Gastric Cancer
Standard treatment options:
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 PDQ Cancer Clinical Trials Registry 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:
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.
Top
Stage I Gastric Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Standard treatment options:
- 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]
- 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 (INT-0116) 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.[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 and relapse-free survival rates were 50% and 48% with adjuvant
chemoradiation therapy versus 41% and 31% 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 and RTOG-9904 trials.[5]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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:
Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996.
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.
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.
Kelsen DP: Postoperative adjuvant chemoradiation therapy for patients with resected gastric cancer: intergroup 116. J Clin Oncol 18 (21 Suppl): 32S-4S, 2000.
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.
Top
Stage II Gastric Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Standard treatment options:
- 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]
- Postoperative chemoradiation therapy.[2]
- Perioperative chemotherapy.[3]
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 (INT-0116) 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.[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 current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in INT-0116.[7] Neoadjuvant
chemoradiation therapy remains under clinical evaluation such as in the SWOG-S0425 and RTOG-9904 trials.[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]
Treatment options under clinical evaluation:
- Postoperative chemoradiation therapy with ECF as evidenced in the CALGB-80101 trial.[7]
- Neoadjuvant chemoradiation therapy as evidenced in the SWOG-S0425 and RTOG-9904 trials.[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 PDQ Cancer Clinical Trials Registry 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:
Brennan MF, Karpeh MS Jr: Surgery for gastric cancer: the American view. Semin Oncol 23 (3): 352-9, 1996.
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.
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.
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.
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.
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.
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.
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.
Top
Stage III Gastric Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Standard treatment options:
- Radical surgery. Curative resection procedures are confined to patients who
at the time of surgical exploration do not have extensive nodal involvement.
- Postoperative chemoradiation therapy.[1]
- Perioperative chemotherapy.[2]
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 (INT-0116) 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 current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in the INT-0116 trial , for example, and the preoperative chemotherapy and chemoradiation therapy regimen used in the RTOG-9904 trial, as another example.
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]
Treatment options under clinical evaluation:
- Postoperative chemoradiation with ECF such as in the CALGB-80101 trial.[3].
- Neoadjuvant chemoradiation therapy such as in the SWOG-S0425 and RTOG-9904 trials.[4]
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 PDQ Cancer Clinical Trials Registry 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:
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.
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.
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.
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.
Top
Stage IV Gastric Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Treatment Options for Patients With No Distant Metastases (M0)
Standard treatment options:
- Radical surgery. Curative resection procedures are confined to patients who
at the time of surgical exploration do not have extensive nodal involvement.
- Postoperative chemoradiation therapy.[1]
- Perioperative chemotherapy.[2]
All patients with tumors that can be resected should undergo surgery. As many as
15% of selected stage IV 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 IV
gastric cancer. A prospective
multi-institution phase III trial (INT-0116) 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 current Cancer and Leukemia Group B study (CALGB-80101) is to augment the postoperative chemoradiation regimen used in the INT-0116trial, for example, and the preoperative chemotherapy and chemoradiation therapy regimen used in the RTOG-9904 trial.
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]
Treatment options under clinical evaluation:
- Postoperative chemoradiation with ECF such as in the CALGB-80101 trial.[3].
- Neoadjuvant chemoradiation therapy such as in the SWOG-S0425 and RTOG-9904 trials.[4]
All newly diagnosed
patients with stage IV gastric cancer should be considered candidates for
clinical trials.
Treatment Options for Patients With Distant Metastases (M1)
Standard treatment options:
- Palliative chemotherapy with:
- Fluorouracil (5-FU).[5][6][7]
- Epirubicin, cisplatin, and 5-FU (ECF).[8][9]
- Cisplatin and 5-FU (CF).[10][7]
- Etoposide, leucovorin, and 5-FU (ELF).[11]
- 5-FU, doxorubicin, and methotrexate (FAMTX).[10]
- Endoluminal laser therapy or endoluminal stent placement may be helpful to
patients whose tumors have occluded the gastric inlet or outlet.[12]
- Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
- 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.[13][14][15][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 HR of 0.83 for OS (95% CI, 0.74–0.93) in favor of combination chemotherapy.[16]
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.[17] The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[17][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).[9][Level of evidence: 1iiA]
An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF.[18] 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%).[18][Level of evidence: 1iiA] There were high toxicity rates in both arms.[19] 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.[19] 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.[10] 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.[10][Level of evidence: 1iiDiv]
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 PDQ Cancer Clinical Trials Registry 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:
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.
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.
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.
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.
Comis RL, Carter SK: Integration of chemotherapy into combined modality treatment of solid tumors. III. Gastric cancer. Cancer Treat Rev 1 (3): 221-238, 1974.
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.
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.
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.
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.
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.
Ajani JA, Ota DM, Jackson DE: Current strategies in the management of locoregional and metastatic gastric carcinoma. Cancer 67 (1 Suppl): 260-5, 1991.
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.
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.
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.
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.
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.
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.
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.
Ilson DH: Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol 25 (22): 3188-90, 2007.
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.
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.
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.
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.
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.
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.
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Recurrent Gastric Cancer
Standard treatment options:
- Palliative chemotherapy with:
- Fluorouracil (5-FU).[1][2][3]
- Epirubicin, cisplatin, and 5-FU (ECF).[4][5]
- Cisplatin and 5-FU (CF).[6][3]
- Etoposide, leucovorin, and 5-FU (ELF).[7]
- 5-FU, doxorubicin, and methotrexate (FAMTX).[6]
- Endoluminal laser therapy or endoluminal stent placement may be helpful to
patients whose tumors have occluded the gastric inlet or outlet.[8]
- Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
- 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.[9][10][11][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 HR of 0.83 for OS (95% CI, 0.74–0.93) in favor of combination chemotherapy.[12]
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.[13] The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[13][Level of evidence: 1iiA] In a second trial that compared ECF with mitomycin, cisplatin, and 5FU (MCF), there was no statistically significant difference in median survival (9.4 vs. 8.7 months, P = .315).[5][Level of evidence: 1iiA]
An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF.[14] 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%).[14][Level of evidence: 1iiA] There were high toxicity rates in both arms.[15] 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.[15] 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.[6] 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.[6][Level of evidence: 1iiDiv]
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.[16][17][18][19][20][21] There are conflicting data regarding relative efficacy of any one regimen over another. Ongoing studies are evaluating these newer regimens.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
recurrent 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:
Comis RL, Carter SK: Integration of chemotherapy into combined modality treatment of solid tumors. III. Gastric cancer. Cancer Treat Rev 1 (3): 221-238, 1974.
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.
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.
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.
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.
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.
Ajani JA, Ota DM, Jackson DE: Current strategies in the management of locoregional and metastatic gastric carcinoma. Cancer 67 (1 Suppl): 260-5, 1991.
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.
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.
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.
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.
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.
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.
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.
Ilson DH: Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol 25 (22): 3188-90, 2007.
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.
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.
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.
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.
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.
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.
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More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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This information is provided by the National Cancer Institute.
This information was last updated on July 2, 2009.