Gastric Cancer Guidelines 

Updated: Apr 13, 2016
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Screening

Gastric cancer is the third leading cause of cancer death worldwide, with the highest rates reported in East Asia, South America and Eastern Europe. The lowest reported incidence is in North America. It is relatively uncommon in the United States, with an estimated 26,370 new cases and 10,730 deaths in 2016. [1]

Although early-detection screening is routine in areas with high disease rates such as Japan and Korea, no major US organization recommends general population screening for gastric cancer. According to the National Cancer Institute (NCI) PDQ cancer information summary for stomach (gastric) cancer screening, there is no evidence that screening would result in a decrease in mortality in areas with relatively low incidence of the disease, such as the US. [2]

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Prevention

Environmental risk factors for gastric cancer include the following:

  • Smoking
  • Diets high in salt, smoked foods, salted fish and meat, and pickled vegetables [1]
  • Helicobacter pylori infection
  • Previous gastric surgery
  • Pernicious anemia
  • Adenomatous polyps
  • Chronic atrophic gastritis
  • Radiation exposure

The National Cancer Institute (NCI) concludes that evidence suggests smoking prevention or cessation would result in a decreased risk of gastric cancer. However, the impact on risk reduction of dietary changes to decrease salt and increase consumption of fruits, vegetables, and whole grains is uncertain. [3]

Management of precancerous conditions

In 2012, the European Society of Gastrointestinal Endoscopy, a group of European gastrological societies (the European Society of Gastrointestinal Endoscopy, the European Helicobacter Study Group, the European Society of Pathology and the Sociedade Portuguesa de Endoscopia Digestiva), published guidelines for the management for precancerous conditions and lesions in the stomach. These guidelines emphasize the increased cancer risk in patients with chronic gastritis, atrophy, intestinal metaplasia, or dysplasia and focus on treatment and surveillance, but do not address general-population screening for these conditions. [4]

The major recommendations include the following [4] :

  • Magnification chromoendoscopy or narrow-band imaging (NBI) endoscopy with or without magnification may be offered for improved diagnosis of pre-neoplastic gastric conditions/lesions
  • At least four biopsies of the proximal and distal stomach, on the lesser and greater curvature, are needed for adequate assessment of premalignant gastric conditions
  • Patients with extensive atrophy and/or extensive intestinal metaplasia should be offered endoscopic surveillance every 3 years
  • Patients with mild to moderate atrophy/intestinal metaplasia only in antrum do not need follow-up
  • If H pylori infection is present, eradication should be offered to prevent high grade dysplasia or carcinoma
  • The use of cyclooxygenase-2 (COX-2) inhibitors or dietary supplementation with antioxidants (ascorbic acid and beta-carotene) are not endorsed as approaches to decrease the risk of progression of gastric precancerous lesions
  • Patients with dysplasia without a visible endoscopic lesion should be closely followed up; those with high grade immediately and 6 to 12 months thereafter; those with low grade, within 12 months
  • Those with dysplasia or cancer within an endoscopically visible lesion should undergo staging and resection.

Helicobacter pylori Infection

H pylori is the most common proven risk factor for non-cardiac gastric cancer. Guidelines for the management of H pylori infection have been issued by the following organizations:

  • American College of Gastroenterology (ACOG)
  • European Helicobacter Study Group

The 2007 ACOG guidelines include the following recommendations [5] :

  • Though there is some evidence to suggest that curing H pylori infection may prevent progression of intestinal metaplasia to gastric adenocarcinoma, whether that can reduce the risk of developing gastric adenocarcinoma remains unknown
  • Testing for H pylori infection is indicated in patients with active peptic ulcer disease, a past history of documented peptic ulcer, or gastric mucosa-associated lymphoid tissue (MALT) lymphoma, after endoscopic resection of early gastric cancer, and uninvestigated dyspepsia
  • In the United States, proton pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole; or a PPI, bismuth, tetracycline, and metronidazole for 10–14 days are accepted first-line treatments for H pylori
  • Eradication rates with a PPI, clarithromycin, and amoxicillin are decreasing worldwide; 14-day courses of therapy are more effective than 7-day regimens

The 2012 European Helicobacter Study Group guidelines note that there is strong evidence that H pylori eradication reduces the risk of gastric cancer, and that the risk of gastric cancer can be reduced more effectively by eradication before the development of preneoplastic conditions. The guidelines recommend that H pylori eradication to prevent gastric cancer be considered in the following [5] :

  • First-degree relatives of family members with a diagnosis of gastric cancer
  • Individuals with previously treated gastric neoplasia
  • Individuals with severe pan-gastritis, corpus-predominant gastritis, or severe atrophy
  • Individuals with chronic gastric acid inhibition for more than 1 year
  • Individuals with other environmental risk factors for gastric cancer (eg, heavy smoking; high exposure to dust, coal, quartz, cement; work in quarries) 

The guidelines recommend that antibiotic combination treatment be chosen according to local H pylori antibiotic resistance patterns. Endoscopic follow-up is recommended for the following preneoplastic high-risk conditions [5] :

  • Pernicious anemia with histological confirmation of type A autoimmune atrophic gastritis
  • Histological and/or serological signs of subtotal or total atrophic gastritis with hypo- or achlorhydria
  • Gastric adenoma

Recommended follow-up intervals are as follows [5] :

  • Patients with moderate to severe atrophy: Every 2–3 years
  • Patients with dysplasia: Every 3–6 months
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Hereditary Cancer Predisposition Syndromes

Hereditary syndromes with a predisposition for stomach cancer include the following:

  • Hereditary diffuse gastric cancer (HDGC)
  • Lynch syndrome (hereditary nonpolyposis colorectal cancer)
  • Familial adenomatous polyposis (FAP)
  • Juvenile polyposis syndrome
  • Peutz-Jeghers syndrome

The following organizations have released guidelines for the evaluation and management of hereditary cancer predisposition syndromes:

  • National Cancer Center Network (NCCN) [6]
  • International Gastric Cancer Linkage Consortium [7]
  • U.S. Multi-Society Task Force on Colorectal Cancer [8]

Hereditary Diffuse Gastric Cancer

HDGC is the most common genetic predisposing syndrome for gastric cancer, with germline truncating mutations of the E-cadherin gene (CDH1) detected in 30-50% of diffuse-type gastric cancers. Families that harbor these mutations have an autosomal dominant pattern of inheritance with a very high penetrance. NCCN guidelines recommendations for CDH1 mutation carriers include the following [6] :

  • The efficacy of endoscopic surveillance has not been established
  • Prophylactic gastrectomy (without a D2 lymph node dissection) between the ages of 18 and 40 for asymptomatic carriers with a family history of HDGC
  • Prophylactic gastrectomy is not recommended before age 18 except in carriers with family members diagnosed with gastric cancer before age 25
  • For individuals who decline prophylactic gastrectomy, upper endoscopy with multiple random biopsies should be considered
  • Women with CDH1 mutations are at increased risk for breast cancer and should be followed similar to BRCA1/ BRCA2 mutation carriers

In 2010, the International Gastric Cancer Linkage Consortium published consensus guidelines for the clinical management of HDGC which are generally in agreement with the NCCN recommendations. [7] The recommendations were also endorsed in the joint guidelines for diagnosis and management of gastric cancer published by the European Society for Medical Oncology(ESM), European Socieity of Surgical Oncology (ESSO) and European Society of Therapeutic Radiation Oncology (ESTRO) in 2013. [8]

Additional recommendation include the following [7] :

  • For those individuals with clinical features suggestive of HDGC but without a germline CDH1 mutation, intensive endoscopic surveillance should also be offered
  • For select carriers with a family history of colon cancer, enhanced screening should be considered with colonoscopy beginning at age 40 or 10 years younger than the youngest age of diagnosis of colon cancer in a family member, whichever is younger, and repeated at intervals of 3–5 years.

Lynch Syndrome (hereditary non-polyposis colorectal cancer)

Although the NCCN guidelines note that gastric cancer is the second most common extracolonic cancer (after endometrial cancer) in patients with Lynch syndrome, they do not find clear evidence to support screening for gastric, duodenal or small bowel cancer. In selected individuals or families of Asian descent, esophagogastroduodenoscopy (EGD) with extended duodenoscopy (to distal duodenum or into the jejunum) every 3-5 years beginning at age 30-35 can be considered. [9]

In 2014, the US Multi-Society Task Force on Colorectal Cancer, which included the American College of Gastroenterology, the American Gastroenterological Association Institute, and the American Society for Gastrointestinal Endoscopy, released consensus guidelines for the genetic evaluation and management of Lynch syndrome. With regard to gastric cancer, the task force recommendations were as follows [10] :

  • Consider screening by esophagogastroduodenoscopy (EGD) with biopsy of the gastric antrum in individuals at risk for or diagnosed with Lynch syndrome at age 30−35 years
  • Treat H pylori infection when found
  • Continue surveillance every 2−3 years, based on individual patient risk factors
  • In view of the relatively low risk of gastric cancer and the lack of established benefit, the 2013 revised guidelines from the Mallorca group for European experts does not recommend surveillance for gastric cancer but does recommend screening individuals with Lynch syndrome for the presence of H pylori infection and subsequent eradication if detected. [11]

Familial Adenomatous Polyposis

The NCCN guidelines recommend examining the stomach at the time of duodenoscopy. Special screening or surgery should only be considered for fundic gland polyps with high-grade dysplasia. Non-fundic gland polyps should be managed endoscopically; polyps with high-grade dysplasia that cannot be removed, or invasive cancer detected on biopsy should be referred for gastrectomy. [9]

Juvenile Polyposis Syndrome and Peutz-Jeghers Syndrome

For both juvenile polyposis syndrome and Peutz-Jeghers syndrome, NCCN guidelines recommend EGD surveillance be considered. For individuals with juvenile polyposis syndrome initial screening should begin at age 15 and performed annually thereafter if polyps are found; if no polyps are found, the test should be repeated every 2-3 years. For Peutz-Jeghers syndrome, screening should begin in late teens and repeated every 2-3 years. [9]

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Diagnosis

NCCN recommendations for diagnosis of gastric cancer are as follows [6] :

  • Endoscopy is the primary procedure for diagnosis, surveillance, and staging of gastric cancer
  • Endoscopic ultrasound (EUS) is preferred in patients with no evidence of M1 disease
  • Multiple biopsies should be performed, especially with ulcerated lesions
  • Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of small lesions (eg, focal nodules ≤2 cm) can be safely performed to provide a larger specimen that may contribute to accurate staging of early-stage cancers; in addition, such excisional biopsies are potentially therapeutic

The European Society for Medical Oncology/ European Society of Surgical Oncology/ European Society for Therapeutic Radiology and Oncology (ESMO-ESSO-ESTRO) guidelines provide similar recommendations. [8]

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Staging

Two major staging systems are commonly used in gastric cancer, as follows:

  • The tumor-node-metastasis (TNM) system, developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) [12]
  • The Japanese Research Society staging, based on where the lymph nodes with cancer are located in the stomach. [13]

Both the NCCN and ESMO use the TNM system for staging. [6, 8] For further information, see Gastric Cancer Staging.

 

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Treatment

National Comprehensive Cancer Network (NCCN) guidelines for treatment of early-stage (Tis, or T1) gastric cancer are as follows [6] :

  • Endoscopic mucosal resection or surgery are the standard treatment options
  • Complete surgical resection offers the potential for long-term survival
  • No further treatment is necessary if there is no residual disease

The NCCN guidelines for treatment of stage IB to IIIC gastric cancer are as follows [6] :

  • For medically fit patients with potentially resectable tumors, preoperative chemotherapy (category 1 recommendation) or chemoradiotherapy followed by surgery is appropriate
  • Postoperative chemoradiation or chemotherapy is indicated for patients who have undergone primary D2 lymph node dissection
  • For patients with unresectable tumors, treatment with fluoropyrimidine- or taxane-based chemoradiotherapy (category 1 recommendation) or chemotherapy is acceptable.

For metastatic gastric cancer, the NCCN recommends palliative chemotherapy or entry into a clinical trial.

For description of chemotherapy and chemoradiotherapy regimens, see Gastric Cancer Treatment Protocols.

The European Society for Medical Oncology/ European Society of Surgical Oncology/ European Society for Therapeutic Radiology and Oncology (ESMO-ESSO-ESTRO) recommendations for treatment are as follows [8] :

  • Multidisciplinary treatment planning is mandatory; the management team should include surgeons, medical and radiation oncologists, gastroenterologists, radiologists, and pathologists plus, if available, dieticians and nurse specialists
  • T1a gastric cancers may be amenable to endoscopic resection if they are well-differentiated, ≤2 cm, confined to the mucosa, and not ulcerated
  • With T1 tumors that do not meet the criteria for endoscopic therapy, lymph node dissection during open surgery can be limited to perigastric nodes and include local N2 nodes
  • The preferred treatment for operable gastric cancers beyond stage T1N0 is surgery with both preoperative and postoperative chemotherapy
  • For patients with stage IB disease or higher who do not receive preoperative chemotherapy, the treatment options include either chemoradiotherapy or chemotherapy in the adjuvant setting
  • Radical gastrectomy is indicated for resectable stage IB–III disease, although subtotal gastrectomy may be performed if a macroscopic proximal margin of 5 cm can be achieved between the tumor and the esophagogastric junction (8 cm for diffuse-type cancers)
  • For medically fit patients, D2 lymph node dissection should be standard
  • For inoperable or metastatic gastric cancer, treatment is with palliative chemotherapy, or best supportive care if the patient is unfit for treatment
  • In HER-2 negative disease, combination regimens based upon a platinum–fluoropyrimidine doublet are generally used; triplet regimens are controversial, but the addition of an anthracycline (eg, epirubicin) has demonstrated benefit
  • In HER-2 positive disease, recommended chemotherapy is with trastuzumab plus cisplatin and either 5-fluorouracil or capecitabine
  • Second-line chemotherapy options include irinotecan and docetaxel or paclitaxel
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