Is an Esophagogastroduodenoscopy (EGD) recommended for individuals with Lynch syndrome?

EGD Surveillance in Lynch Syndrome

EGD surveillance should be considered for selected individuals with Lynch syndrome, particularly those with MLH1, MSH2, or EPCAM mutations, starting at age 30-35 years and repeated every 2-3 years, with stronger consideration for those of Asian descent or with family history of gastric cancer. 1

Evidence-Based Rationale

Risk Stratification by Gene Mutation

The lifetime risk of gastric cancer varies dramatically by population and genetic mutation:

• High-risk mutations (MLH1, MSH2, EPCAM): Gastric cancer risk reaches 3-5% by age 70-75, with duodenal cancer risk of 5-6% 2
• Low-risk mutations (MSH6, PMS2): Gastric cancer risk remains ≤1% and duodenal cancer risk 1-2% by age 75 2
• Geographic variation: Risk ranges from 2-4% in Western populations to 30% in Korean populations 1

Surveillance Effectiveness

Recent high-quality research demonstrates meaningful detection rates:

• Cancer detection: 1.5% of asymptomatic Lynch syndrome patients had upper GI cancers detected during surveillance, all at early stage 3
• Early-stage detection: 71% of duodenal cancers were detected at early stage in surveillance groups versus only 29% in non-surveillance groups (p=0.021) 4
• Clinically actionable findings: Approximately 17.6% of patients had findings requiring intervention (neoplasia, Barrett's esophagus, H. pylori, or large hyperplastic polyps) 3
• Meta-analysis pooled rates: 0.9% cancer detection, 4.2% high-risk lesions, and 6.2% clinically actionable findings per screening episode 5

Current Guideline Recommendations

NCCN Guidelines (2016) state there is no clear evidence to support routine screening for gastric, duodenal, and small bowel cancer in all Lynch syndrome patients, but recommend physicians may consider EGD extended to the distal duodenum or jejunum every 3-5 years starting at age 30-35 for: 1

• Selected individuals or families with gastric cancer history
• Those of Asian descent
• Carriers of MLH1, MSH2, or EPCAM mutations

US Multi-Society Task Force (2014) recommends screening should be considered by EGD of the antrum at age 30-35 years with treatment of H. pylori when found, with subsequent surveillance every 2-3 years based on individual risk factors 1

AGA Guidelines (2015) do not specifically address upper endoscopy surveillance, focusing primarily on colonoscopy 1

Practical Implementation Algorithm

Who Should Undergo EGD Surveillance:

Strongly consider for:

• MLH1, MSH2, or EPCAM mutation carriers of Asian descent 1
• Any Lynch syndrome patient with family history of gastric or duodenal cancer 1
• Males (stronger predisposition to gastric cancer) 1

May consider for:

• All MLH1, MSH2, or EPCAM mutation carriers starting age 30-35 1

Generally not recommended for:

• MSH6 or PMS2 mutation carriers without additional risk factors (very low risk before age 50) 2
• Any Lynch syndrome patient under age 25-30 (cumulative incidence ≤1% before age 50) 2

Surveillance Protocol:

• Starting age: 30-35 years 1
• Interval: Every 2-3 years (NCCN suggests 3-5 years, but Multi-Society Task Force recommends 2-3 years) 1
• Extent: Extended to distal duodenum or into jejunum, not just standard EGD 1
• H. pylori management: Test and treat if positive given increased gastric cancer risk 1

Surveillance Findings Requiring Action:

• Any adenoma or dysplasia: Increased surveillance frequency 3
• Barrett's esophagus: Standard Barrett's surveillance protocols 3
• Hyperplastic polyps >5mm: Follow-up surveillance 3
• H. pylori infection: Eradication therapy 1

Critical Pitfalls to Avoid

Do not dismiss the value of baseline EGD: 27.7% of clinically actionable findings were identified on the first examination, with the remainder detected over an average of 3.5 years of follow-up 3

Do not use standard EGD technique: Examination must be extended to the distal duodenum or jejunum, as approximately 50% of small bowel cancers in Lynch syndrome are duodenal 1, 4

Do not delay surveillance based on lack of family history: Family and personal tumor history did not correlate with duodenal cancer diagnosis, and 10% of cases occurred before age 35 4

Do not assume low-risk mutations eliminate all risk: While MSH6 and PMS2 carriers have substantially lower risk, surveillance may still be considered based on family history or other risk factors 2

Do not extend intervals beyond 3 years: Two interval cancers were detected at 1.7 and 2.7 years after prior normal EGD, suggesting that longer intervals may miss cancers 6

Nuances and Divergent Evidence

The evidence base shows some inconsistency in recommendations:

• Interval controversy: NCCN suggests 3-5 years 1, while the Multi-Society Task Force recommends 2-3 years 1, and research data suggest interval cancers can occur within 2-3 years 6
• Age to start: Most guidelines converge on 30-35 years, but one study suggests starting no later than age 25 given that 10% of duodenal cancers occurred before age 35 4
• Gene-specific recommendations: Recent data clearly show MSH6 and PMS2 carriers have much lower risk 2, but older guidelines do not differentiate surveillance by specific mutation

The strongest and most recent evidence from 2024 2 demonstrates that risk before age 50 is very low (≤1%) for all Lynch syndrome patients, suggesting that earlier surveillance (before age 30) is not warranted, while surveillance becomes more justified after age 50-60 for high-risk mutation carriers.