What surveillance is recommended for individuals with a strong family history of gastric cancer?

Surveillance for Family History of Gastric Cancer

For individuals with a strong family history of gastric cancer, surveillance recommendations depend critically on whether hereditary diffuse gastric cancer (HDGC) is present: if HDGC criteria are met, genetic testing for CDH1 mutations is mandatory, with prophylactic total gastrectomy recommended between ages 20-30 for mutation carriers; for non-hereditary familial gastric cancer, screening EGD every 3-5 years is recommended starting at age 40-50 (or 10 years before the youngest affected relative's diagnosis), with mandatory H. pylori eradication if present. 1, 2

Step 1: Determine if HDGC Criteria Are Met

First, assess whether the family meets International Gastric Cancer Linkage Consortium (IGCLC) criteria for HDGC genetic testing: 1

• Two or more documented cases of gastric cancer at any age in first- or second-degree relatives, with at least one confirmed diffuse gastric cancer 1
• Personal history of diffuse gastric cancer before age 40 years 1
• Personal or family history of diffuse gastric cancer AND lobular breast cancer, with one diagnosed before age 50 1

If any criterion is met, proceed immediately to CDH1 genetic testing (including both DNA sequencing and large rearrangement analysis). 1

Step 2: Management for Confirmed CDH1 Mutation Carriers

For pathogenic CDH1 mutation carriers, prophylactic total gastrectomy between ages 20-30 is the definitive recommendation to prevent mortality from diffuse gastric cancer (70% lifetime risk in men, 56% in women by age 80). 1, 2

If Gastrectomy Is Declined or Delayed:

• Annual endoscopy surveillance with a minimum of 28-30 random biopsies (3-5 cardia, 5 fundus, 10 body, 5 transition zone, 5 antrum) 1, 2
• Surveillance must be performed at expert centers familiar with HDGC 1
• Any malignant lesion detected on biopsy mandates immediate curative total gastrectomy, regardless of age 1

Critical caveat: Endoscopic surveillance is imperfect—cancer foci are often endoscopically invisible and may be missed despite adherence to biopsy protocols. 3 Patients must understand this limitation when choosing surveillance over prophylactic gastrectomy. 1

Additional Surveillance for CDH1 Carriers:

• Annual breast MRI starting at age 30 for female mutation carriers (42% lifetime risk of lobular breast cancer) 1
• Annual mammography from age 40 (may consider from age 35-40 on case-by-case basis) 1

Step 3: Management for Familial Intestinal Gastric Cancer (Non-HDGC)

For families with intestinal-type gastric cancer clustering without polyposis or CDH1 mutations, no robust surveillance recommendations exist, but a pragmatic approach is warranted: 1

• Screen with EGD every 3-5 years starting at age 40-50, or 10 years before the youngest affected relative's age at diagnosis 2, 4, 5
• Mandatory H. pylori testing and eradication in all family members (synergistic effect with family history increases gastric cancer risk) 1, 2, 4
• Consider initiating H. pylori eradication at age 20 before precancerous lesions develop 4
• If atrophic gastritis or intestinal metaplasia is detected, shorten surveillance interval to every 1-2 years 4, 6

High-Quality Screening EGD Must Include:

• Systematic gastric biopsies if atrophy or metaplasia is suspected 2
• Targeted biopsies of any visual abnormalities 2
• Image-enhanced endoscopy techniques when available 2

Step 4: Special Considerations for Polyposis Syndromes

For familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): 1

• Upper endoscopy surveillance starting at age 25-30 years 1
• Continue surveillance every 1-5 years based on Spigelman stage for duodenal polyps 1
• Individualized management for GAPPS, including endoscopic surveillance with random biopsies or polypectomies, and eventual prophylactic gastrectomy 1

Common Pitfalls to Avoid

Do not apply HDGC protocols to all family history cases—HDGC requires distinct genetic testing and management. 2 Most familial gastric cancer is non-hereditary intestinal type. 1

Do not rely on endoscopy alone in CDH1 carriers—surveillance has significant limitations, and prophylactic gastrectomy remains the gold standard for mortality reduction. 1, 3

Do not neglect H. pylori eradication—this is the single most modifiable risk factor in familial gastric cancer and must be addressed in all family members. 1, 2, 4

Consider ethnicity and immigrant status—individuals from high-incidence regions (East Asia, Eastern Europe, South America) warrant more aggressive screening even with limited family history. 2, 5

Algorithm Summary

1. Assess IGCLC criteria → If met, order CDH1 genetic testing 1, 2
2. If CDH1 positive → Prophylactic gastrectomy age 20-30 OR annual endoscopy with 28-30 biopsies 1, 2
3. If CDH1 negative or familial intestinal type → EGD every 3-5 years starting age 40-50 (or 10 years before youngest affected relative) + H. pylori eradication 2, 4, 5
4. If atrophy/metaplasia detected → Shorten interval to 1-2 years 4, 6
5. If polyposis syndrome → Start surveillance age 25-30, interval based on polyp burden 1