Endoscopic Surveillance in Patients at Risk for Hereditary Diffuse Gastric Cancer

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In a prospective cohort study reported in The Lancet Oncology, Asif et al found that endoscopic surveillance may be an alternative to prophylactic total gastrectomy in patients at risk for hereditary diffuse gastric cancer due to germline CDH1 pathogenic variants.

Study Details

In the study, 270 patients (median age = 47 years) with germline CDH1 variants underwent endoscopic screening and surveillance between January 2017 and December 2021 at the National Institutes of Health as part of a natural history study of hereditary gastric cancers. Endoscopy was performed with nontargeted biopsies and at least one targeted biopsy and assessment of focal lesions. Screening was defined as the initial endoscopy, with all subsequent endoscopies considered surveillance; follow-up endoscopy was at 6 to 12 months. The primary aim was to assess the effectiveness of endoscopic surveillance for detection of gastric signet ring cell carcinoma.

Key Findings

Among the 270 patients, 213 (79%) had a family history of gastric cancer and 176 (65%) had a family history of breast cancer.

Median follow-up was 31.1 months (interquartile range = 17.1–42.1 months). A total of 467 endoscopies were performed as of data cutoff in April 2022. Among 38,803 gastric biopsy samples obtained, 1,163 (3%) were positive for invasive signet ring cell carcinoma.

Signet ring cell carcinoma was detected in 76 (63%) of 120 patients who had two or more surveillance endoscopies; of these, 74 had occult cancer detected and 2 had focal ulcerations corresponding to pT3N0 stage carcinoma.

A total of 98 (36%) of 270 patients proceeded to prophylactic total gastrectomy. Among 42 (43%) of the 98 patients who had prophylactic total gastrectomy after endoscopy with biopsy samples negative for cancer, multifocal stage IA gastric carcinoma was detected in 39 (93%).

No patients were diagnosed with stage III or IV gastric cancer during follow-up.

Two patients died during follow-up, one due to metastatic lobular breast cancer and the other due to underlying cerebrovascular disease.

The investigators concluded, “In our cohort, endoscopic cancer surveillance was an acceptable alternative to surgery in individuals with CDH1 variants who declined total gastrectomy. The low rate of incident tumors (> T1a) suggests that surveillance might be a rational alternative to surgery in individuals with CDH1 variants.”

Jeremy L. Davis, MD, of the Surgical Oncology Program, National Cancer Institute, is the corresponding author for The Lancet Oncology article. 

Disclosure: The study was funded by the Intramural Research Program of the National Institutes of Health. For full disclosures of the study authors, visit

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