Last updated:
May 12, 2021
Years published: 2019
NORD gratefully acknowledges Brian D. Badgwell, MD, Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, for assistance in the preparation of this report.
Stomach cancer is a general term for cancer affecting the stomach. Generally, it refers to cancer that arises from the cells lining the stomach. These cells, like all cancerous cells, exhibit abnormal and rapid growth. Early in the course of the disease there are usually no symptoms (asymptomatic). As the disease progresses, symptoms like indigestion, nausea, vomiting, and feeling full earlier than normal (early satiety) may develop. The cause of stomach cancer is multifactorial, which means that multiple factors that occur together are necessary for the cancer to develop. These factors can include genetic, immunologic, infectious, and environmental factors. Stomach cancer usually develops randomly for unknown reasons (sporadically), and there is usually no family history.
There are several different forms of stomach cancer. The most common is called adenocarcinoma, which accounts for about 90-95% of people with stomach cancer. Other types include primary gastric lymphoma, gastrointestinal stromal tumor (GIST), and neuroendocrine (carcinoid) tumors in the stomach. NORD has information on these forms of cancer – for more information choose the specific cancer name as your search term in the Rare Disease Database. In rare instances, other forms of cancer can arise in the stomach including squamous cell carcinoma, small cell carcinoma, and leiomyosarcoma. Malignancies in other organs rarely metastasize to the stomach, although breast cancer is one malignancy that can spread to the stomach in very rare circumstances. This report primarily deals with adenocarcinoma of the stomach or gastroesophageal junction.
The stomach is the organ where the main part of digestion occurs. The stomach is connected to the esophagus (a tube that is connected to the throat) at the gastroesophageal junction. After food is chewed and swallowed it travels down the throat, through the esophagus and into the stomach. The bottom part of the stomach is connected to the small intestine called the duodenum. Stomach cancer (adenocarcinoma) can occur anywhere in the stomach, but most often arises from the cells making up the mucus membrane lining the stomach (mucus-producing cells). When cancer forms near the esophagus, it may be referred to as cancer of the gastroesophageal junction.
The signs and symptoms can vary greatly from one person to another. Specific findings depend on numerous factors including the exact location of the tumor, the extent of the tumor into nearby tissue or organs, the specific organs involved, and whether the disease has remained localized or spread to other areas of the body (metastasized). Stomach cancer is a slow-growing cancer that usually develops over a year or longer.
Generally, there are no symptoms in the early stages (asymptomatic). As the disease progresses, a variety of symptoms can develop. These symptoms include indigestion (dyspepsia), which can be severe and persistent, nausea, vomiting, feeling full after eating a small amount of food (early satiety), feeling bloated after eating, and severe, persistent heartburn. Sometimes, stomach discomfort or pain, difficulty swallowing (dysphagia), fatigue, and unintended weight loss can occur. Pain is mild and vague early in the disease, but becomes more severe and constant as the disease progresses.
Loss of blood from the stomach can occur and can go unnoticed leading to anemia (low levels of circulating red blood cells). Anemia can lead to fatigue, paleness of skin, and shortness of breath. Although uncommon, in advanced cases, affected individuals may vomit blood (hematemesis) or have dark, sticky feces (melena) due to blood in the stools.
Sometimes, the first signs or symptoms of stomach cancer occur after the cancer has spread to other areas of the body. Exact symptoms will depend upon where the cancer spreads to, but common symptoms include inability to tolerate any oral intake due to bowel obstruction, fractures, neurologic changes, and swelling of the abdomen due to the buildup of fluid (ascites).
Some other signs of advanced disease include a mass in the upper, center region of the abdomen (epigastric mass) or enlargement of the liver (hepatomegaly).
The exact, underlying cause of stomach cancer is not fully understood. The reason why cancer develops is a complex question and researchers speculate that multiple factors are involved in the development of gastric cancer. These factors can include genetic, environmental, infectious, and immunologic factors.
In most people, stomach cancer develops randomly without a family history (sporadically). Often, cancer is associated with different genes, which are linked to cancer’s development. When a variation (mutation of the DNA) of a cancer-associated gene occurs, the protein product created by that gene may be faulty, inefficient, absent, or overproduced. Variations in genes associated with cancer have been shown to increase a person’s risk of developing cancer (genetic predisposition). A genetic predisposition means that a person has a gene or genes for a disease, but the disease will not develop unless additional genetic or environmental factors are also present. These variations are somatic mutations and can occur in any cell of the body except the germ cells (the egg or the sperm). Consequently, these variations are not inherited and are acquired during life. Understanding the underlying genetic factors in stomach cancer is important and can lead to better, more targeted therapies in the future.
In rare instances, stomach cancer can run in families. Having a first-degree relative with stomach cancer is considered a risk factor for the disease. In some these families, there may be an associated mutation with known risk factors that accounts for multiple family members being affected. For example, there can be clustering of H. pylori infection within families or there may be a predisposition to chronic inflammation of the mucous membrane lining the stomach (chronic atrophic gastritis).
There are hereditary cancer syndromes (genetic disorders) that increase a person’s risk of develop stomach cancer (and often other types of cancer as well). About 1-3% of people with stomach cancer have an inherited cancer predisposition syndrome. These are inherited disorders in which affected individuals have a greater risk than the general population of developing cancer. These syndromes include hereditary diffuse gastric cancer (CDH1 mutations), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), familial intestinal gastric cancer (FIGC), hereditary breast and ovarian cancer (HBOC) syndrome (due to variations in the BRCA1 or BRCA2 gene); Lynch syndrome, which is also called hereditary non-polyposis colorectal cancer; familial adenomatous polyposis; Li-Fraumeni syndrome; and Peutz-Jeghers syndrome.
Several different environmental factors have been associated with stomach cancer. Infection with Helicobacter pylori (H. pylori) is strongly associated with stomach cancer, especially cancer of the lower portion of the stomach. H. pylori is a type of bacterial infection that arises in the mucus layer of tissue that lines the stomach. This infection can cause inflammation and ulcers within the stomach. Long-term or chronic H. pylori infection is associated with marked inflammation and precancerous changes in the cells of the lining of the stomach. Most people who have H. pylori infection in the stomach never develop stomach cancer.
Individuals who have a rare cancer called mucosa-associated lymphoid tissue (MALT) lymphoma are at a greater risk than the general population of developing adenocarcinoma of the stomach. Individuals with certain disorders including pernicious anemia, combined variable immunodeficiency, or Menetrier disease (hypertrophic gastropathy) are also at an increased risk of stomach cancer. There are noncancerous (benign), small growths (polyps) commonly found in the stomach. Many people have these polyps. A specific type of polyp called an adenoma can change and become cancerous.
People who have had previous surgery on the stomach, such as for ulcers, are at an increased risk as well. Some studies suggest that a person’s diet can influence stomach cancer risk and that a diet high in salt and foods smoked or pickled in salt including certain meats or salted fish can increase the risk of stomach cancer. There are studies showing that a diet high in fried food, processed meats, and fish can increase the risk of stomach cancer. There are also studies that have shown that eating fruits and vegetables may help to prevent stomach cancer.
The rate of stomach cancer is doubled in people who smoke. Smoking particularly increases the risk of stomach cancer near the esophagus. There is also an increased risk in people who work in certain industries where they are exposed to toxic materials including coal, metal, rubber industries (occupational exposure). Although the reason why is not known, people with type A blood also have a slightly increased risk of stomach cancer. Other potential factors have been suggested including obesity, alcohol consumption, and infection with Epstein-Barr virus, but the evidence is contradictory and such associations remain unproven.
Gastroesophageal junction cancer can be associated with gastroesophageal reflux (GERD). GERD is a condition in which the contents of the stomach flow backward into the lower part of the esophagus.
There are about 28,000 people diagnosed with stomach cancer in the United States each year. It affects men more often than it does women, and about 75% of people are over the age of 50. Most people are diagnosed between 60-80 years of age. By some estimates, stomach cancer is the second most common cancer worldwide. Stomach cancer can affect people of all races and ethnic groups but occurs with greater frequency in individuals of African or Hispanic heritage and Native Americans. Worldwide, stomach cancer is more common in East Asia, Eastern Europe, and South America.
A diagnosis of stomach cancer is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Because stomach cancer does not usually cause symptoms in the early stages of the disease, it is often not diagnosed until the disease is advanced. There is no screening program for stomach cancer in the United States or Europe, although there are programs in other countries including Japan and Korea.
Clinical Testing and Workup
A complete blood count is a standard blood test. This test can be ordered if stomach or gastrointestinal cancer is suspected to detect low levels of circulating red blood cells (anemia), which can occur due to blood loss. Another test that can be ordered is a fecal occult blood test. This test examines the stool for the presence of blood that is not visible to the naked eye.
Doctors may order an upper endoscopy examination in individuals suspected of stomach cancer. This examination allows doctors to view the upper portion of the digestive tract including the esophagus, stomach, and the duodenum. During this examination, doctors will run a thin, flexible tube down a person’s throat. This tube has a tiny camera attached to it that allows doctors to visually inspect these areas. If an abnormal growth or abnormal tissue is seen, doctors can pass instruments through the tube that allow them to remove a sample of tissue.
Any tissue samples that are taken are then viewed under a microscope. The surgical removal and microscopic examination of a tissue sample is called a biopsy. This biopsy sample is then studied by a pathologist, who is a specialist trained in examining tissues and cells to find disease and determine what disease is present.
Doctors may also order advancing imaging (x-ray) techniques, specially computed tomography along with endoscopic ultrasonography. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Doctors will examine the chest and abdomen to determine whether stomach cancer has spread (metastasized) to these sites.
An endoscopic ultrasonography is performed to determine the depth and exact location of the tumor and determine whether the cancer has spread into the wall of the stomach or is affecting any of the nearby lymph nodes. Ultrasounds use high-frequency radio waves to create a picture or image (sonogram) of specific structures like internal organs. The radio waves bounce off of (echo) internal structures within the body and the echoes are recorded to create a sonogram.
Sometimes, a double-contrast gastrointestinal series may be recommended. This examination uses x-rays along with a barium swallow. Barium is a chalky, white, metallic element. An affected individual will swallow a solution containing barium, which coats the esophagus, stomach, and small intestines. X-rays cannot pass through barium so the x-ray file will be able to outline structures or tissues in these areas. This will help doctors determine the presence and extent of the disease.
In some instances, doctors may recommend laparoscopy or laparotomy to obtain biopsy samples and help stage the cancer. Laparoscopy involves examination of the abdominal cavity with an illuminated viewing tube (laparoscope) inserted through incisions in the abdominal wall. Laparotomy is a surgical procedure in which the abdomen is opened, organs are carefully examined to detect signs of disease, and samples of tissue are removed for microscopic examination. Sometimes, fluid samples are taken and studied. This can include fluid from the abdomen when ascites is present.
Staging
When an individual is diagnosed with stomach cancer, assessment is also required to determine the extent or “stage” of the disease. Staging is important to help characterize the potential disease course and determine appropriate treatment approaches. A variety of diagnostic tests may be used in staging stomach carcinoma (e.g., blood tests, CT scanning,). Stomach cancer can be staged by the American Joint Committee on Cancer (AJCC)/the Union for International Cancer Control (UICC) system, which is based on the Tumor, Node, Metastasis (TNM) classification system. Information on this staging system for stomach cancer is available from the American Cancer Society at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/staging.html
Treatment
The therapeutic management of individuals with stomach cancer may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of diseases of the digestive system (gastroenterologists), physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who specialize in the diagnosis and treatment of cancer with surgery (surgical oncologists), physicians who specialize in the use of radiation therapy for treatment of cancer (radiation oncologists), oncology nurses, psychiatrists, nutritionists, and other healthcare specialists. Psychosocial support for the entire family is essential as well.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; specific stomach cancer subtype; whether the cancer has spread; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.
Surgery is a main therapeutic option for stomach cancer. The exact surgery and extent of surgery depends upon the type and stage of the cancer. Surgery can include endoscopic resection, in which the cancer has not spread to nearby lymph nodes. Surgeons run a thin, flexible tube down the throat to the stomach. They are able to guide tools down the tube that allow them to surgically remove the tumor and any affected tissue from the stomach wall. Gastric cancer diagnosed in the United States is rarely thin and small enough to allow for endoscopic resection. In addition, this technique is dependent upon the expertise of the physician performing the procedure.
For most patients with gastric cancer confined to the stomach and adjacent lymph nodes, surgeons need to remove some of the stomach along with the tumor. This is called a subtotal (partial) gastrectomy. If the cancer is in the upper part of the stomach, sometimes some of the esophagus may also need to be removed. If the cancer is in the lower part of the stomach, sometimes some of the upper portion of the lower intestines called the duodenum may need to be removed.
Sometimes, surgeons must remove the entire stomach and some of the surrounding tissue. This is called a total gastrectomy. It is most often recommended when cancer has spread throughout the stomach. During this surgery the end of the esophagus is connected directly to the duodenum to allow the passage of food.
A common part of the surgery to remove part or all of the stomach is to remove adjacent lymph nodes. This part of surgery may be referred to as lymph node dissection or lymphadenopathy.
Sometimes chemotherapy or radiation therapy may be before or after surgery. This is called neoadjuvant or adjuvant therapy. When used along with surgery, chemotherapy may be given before surgery (neoadjuvant) to shrink a tumor or following surgery (adjuvant) to eliminate any remaining cancer cells and lessen the risk of a recurrence. Sometimes, chemotherapy may be given before and after surgery (perioperative). Different combinations of medications may be used; this is called a chemotherapy regimen. When chemotherapy is given, the specific chemotherapy regimen used can vary. Different medical centers may have their own preferences as to the best way to approach treatment and what chemotherapeutic regimen is best for each individual.
5FU/leucovorin and oxaliplatin are often used as the first therapy for the treatment of stomach cancer that is locally advanced or has spread to other parts of the body. Docetaxel (Taxotere) is approved for adenocarcinoma of the stomach or gastroesophageal junction that is advanced in people who have not been treated with chemotherapy for advanced disease.
Radiation therapy may also be used as an adjuvant therapy. Radiation therapy is the use of high doses of radiation to kill cancer cells and shrink tumors. Radiation therapy preferentially destroys or injures rapidly-dividing cells, primarily cancerous cells. Radiation is passed through affected tissue to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages the cells’ genetic material, preventing or slowing their growth and replication. Radiation therapy is sometimes given at the same time as chemotherapy (chemoradiotherapy). For example, when treating cancer of the gastroesophageal junction chemoradiotherapy is often given following surgery.
The eradication of H. pylori infection with antibacterial medications is important.
TARGETED THERAPIES
Targeted therapies target a specific molecule, protein or substance in order to block the growth and spread of cancer rather than destroy cancer cells (cytotoxic treatments) like chemotherapy or radiation therapy. Targeted therapies are less likely to damage healthy cells. There are a few targeted therapies that have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of stomach cancer.
In 2010, the FDA approved Herceptin (trastuzumab) along with chemotherapy for the treatment of stomach or gastroesophageal cancer (adenocarcinomas) that produce too much HER2 protein and has spread (metastasized). Affected individuals must have not yet received other treatment for metastatic disease.
In 2015, the FDA approved Cyramza (ramucirumab) for the treatment of advanced stomach cancer or gastroesophageal junction cancer that has not responded to other treatments.
In 2017, the FDA granted accelerated approval of Keytruda (pembrolizumab) for the treatment of stomach cancer or gastroesophageal junction cancer that is recurrent and locally advanced or has spread (metastatic). It is approved for affected individuals whose cancer has the PD-1 protein and has worsened despite two or more other therapies. Pembrolizumab is a type of new therapy called immunotherapy. This type of treatment aims to enhance the body’s innate ability to fight cancer cells using the immune system. For example, the most common form of immunotherapy called PD-1 or PD-L1 blockade releases the “brakes” on the immune system that some cancers use to try to evade the immune cells.
Most recently, in 2021, the FDA approved Opdivo (nivolumab) in combination with certain types of chemotherapy for the initial treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma. This is the first FDA-approved immunotherapy for the first-line treatment of gastric cancer.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Allum W, Lordick F, Alsina M, et al. ECCO essential requirements for quality cancer care: oesophageal and gastric cancer. Crit Rev Oncol Hematol. 2018;122:179-193. https://www.ncbi.nlm.nih.gov/pubmed/29458786
Noto JM, Peek RM Jr. The gastric microbiome, its interaction with Helicobacter pylori, and its potential role in the progression to stomach cancer. PLoS Pathog. 2017;13:e1006573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629027/
Goode EF, Smyth EC. Immunotherapy for gastroesophageal cancer. J Clin Med. 2016;5:84. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086586/
Kilic L, Ordu C, Yildiz I, et al. Current adjuvant treatment modalities for gastric cancer: from history to the future. World J Gastrointest Oncol. 2016;8:349-449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865711/
Petrovchich I, Ford JM. Genetic predisposition to gastric cancer. Semin Oncol. 2016;43:554-559. https://www.ncbi.nlm.nih.gov/pubmed/27899187
Sitas F. Twenty five years since the first prospective study by Forman et al. (1991) on Helicobacter pylori and stomach cancer risk. Cancer Epidemiol. 2016;41:159-164. https://www.ncbi.nlm.nih.gov/pubmed/26922171
Sehdev A, Catenacci DV. Gastroesophageal cancer: focus on epidemiology, classification, and staging. Discov Med. 2013;16:103-11. https://www.ncbi.nlm.nih.gov/pubmed/23998446
INTERNET
National Cancer Institute. Gastric Cancer Treatment (PDQ®) – Patient Version. August 16, 2018. Available at: https://www.cancer.gov/types/stomach/patient/stomach-treatment-pdq Accessed On: August 24, 2018.
Livstone EM. Stomach Cancer. Merck Manual Online Professional Version website. Updated October 2017. Available at: https://www.merckmanuals.com/professional/gastrointestinal-disorders/tumors-of-the-gi-tract/stomach-cancer Accessed August 24, 2018.
Mayo Clinic for Medical Education and Research. Cervical Dystonia. May 19, 2018. Available at: https://www.mayoclinic.org/diseases-conditions/stomach-cancer/symptoms-causes/syc-20352438 Accessed On: August 24, 2018.
American Cancer Society. Stomach Cancer. Available at: https://www.cancer.org/cancer/stomach-cancer.html Accessed On: August 24, 2018.
Cabebe EC. Gastric Cancer. Emedicine Journal, April 30, 2018. Available at: https://emedicine.medscape.com/article/278744-overview Accessed on: August 24, 2018.
European Society for Medical Oncology. Stomach Cancer. V.2012.1. Available at: https://www.esmo.org/content/download/6635/115239/file/EN-Stomach-Cancer-Guide-for-Patients.pdf Accessed August 24, 2018.
Mansfield PF. Clinical features, diagnosis, and staging of gastric cancer. UpToDate, Inc. 2017 Nov 14. Available at: https://www.uptodate.com/contents/clinical-features-diagnosis-and-staging-of-gastric-cancer Accessed on: August 27, 2018.
Morgan D. Early gastric cancer: treatment, natural history, and prognosis. UpToDate, Inc. 2018 Nov 24. Available at: https://www.uptodate.com/contents/early-gastric-cancer-treatment-natural-history-and-prognosis Accessed on: August 27, 2018.
Chan AOO, Wong B. Risk factors for gastric cancer. UpToDate, Inc. 2016 Sep 26. Available at: https://www.uptodate.com/contents/risk-factors-for-gastric-cancer Accessed on: August 27, 2018.
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