Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome

Abstract

Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer surveillance in Lynch syndrome remains more controversial. Currently, upper gastrointestinal cancer surveillance guidelines for Lynch syndrome vary widely, and there is no consensus on who should undergo upper gastrointestinal cancer surveillance, how surveillance should be performed, the age at which to initiate surveillance, or how often individuals with Lynch syndrome should undergo upper gastrointestinal cancer surveillance. Fortunately, research groups around the world have been focusing on upper gastrointestinal cancer surveillance in Lynch syndrome, and recent evidence in this field has demonstrated that upper gastrointestinal cancer surveillance can be performed with identification of precancerous lesions as well as early-stage upper gastrointestinal cancers. In this manuscript, we review the upper gastrointestinal cancer risks in Lynch syndrome, differing guideline recommendations for surveillance, outcomes of upper gastrointestinal cancer surveillance, and controversies in the field, and we provide a framework based on our collective experience with which to incorporate upper gastrointestinal cancer surveillance into a risk management program for individuals with Lynch syndrome.

Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

“…LS due to a PV in MLH1 , MSH2 , MSH6 , PMS2 , or EPCAM is one of the most common gastric cancer predisposition syndromes, affecting 1 in 279 individuals 145 . Gastric cancer risk in LS can be up to 9 per cent, however, but varies by genotype, with PMS2 variants associated with lower gastric cancer risk than other variants 125 . Male sex, having an FDR with gastric cancer, and older age are also associated with a higher risk of gastric cancer in LS 146 .…”

“…Studies of gastric surveillance in LS from the USA 147–149 and Europe 125 , 150 have illustrated that surveillance leads to clinically actionable findings as well as early-stage gastric cancers. A recent meta-analysis of upper gastrointestinal surveillance demonstrated that the pooled event rate for detecting an upper gastrointestinal cancer was 0.9 per cent, a high-risk lesion was 4.2 per cent, and an actionable finding was 6.2 per cent 151 .…”

Endoscopic Surveillance in Patients with the Highest Risk of Gastric Cancer: Challenges and Solutions

“…Multiple professional societies have developed guidelines addressing management of gastric cancer risk in Lynch syndrome. 35,[41][42][43][44][45][46][47][48] However, significant heterogeneity exists at present between these guidelines regarding whether gastric surveillance should be performed, the age of initiation, and recommended interval for upper GI surveillance in Lynch syndrome, which has been well-summarized in a recent review by Kumar et al 49 In part, the variability of different guidelines has resulted from limited data demonstrating clinical effectiveness of gastric cancer surveillance in Lynch Cancer Management and Research 2022:14 https://doi.org/10.2147/CMAR.S277898 DovePress 2957 syndrome, as well as uncertainty regarding which high-risk individuals are most in need of surveillance. Fortunately, this is an area of ongoing active research, with recent studies of upper endoscopic surveillance in Lynch syndrome supporting surveillance as effective at detecting pre-cancerous lesions and early-stage gastric cancers.…”

“…It is the authors’ practice that all individuals with Lynch syndrome, regardless of the causative gene, initiate surveillance upper endoscopy at age 30 (or 2–5 years before the youngest age of diagnosis if there is a family history of gastric cancer under age 35), repeating every 2–3 years with consideration of shorter intervals with a family history of upper GI cancer or in the presence of precancerous lesions (incomplete or extensive gastric intestinal metaplasia, gastric/duodenal adenoma or Barrett’s esophagus with dysplasia). 49 NCCN recently adopted a similar approach by recommending upper GI surveillance starting between ages 30–40 and repeating every 2–4 years for all MLH1, MSH2/EPCAM , and MSH6 PV carriers with consideration of upper GI surveillance in PMS2 PV carriers. 35 Surveillance should also be performed with use of high definition, white light endoscopy, ideally performed at the time of surveillance colonoscopy, with inclusion of random biopsies of the proximal and distal stomach to evaluate for Helicobacter pylori , intestinal metaplasia and autoimmune gastritis.…”

“…Push enteroscopy may also be considered instead of standard upper endoscopy to improve the extent of small bowel visualization, however more study is needed addressing the yield in Lynch syndrome. 35 , 49 , 56 Future research in upper GI surveillance in Lynch syndrome needs to focus on whether upper GI surveillance leads to a survival benefit and is cost-effective, as well as understanding the mechanism of Lynch syndrome-associated gastric carcinogenesis.…”