Mian B. Khalid, MD
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Gracia Viana-Rodriguez, MD
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Disha Sharma, MD
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Amber F. Gallanis, MD
Surgical Oncology Research Fellow
National Cancer Institute
Arlington, Virginia, United States
Christopher Koh, MHSc
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Sheila Kumar, MD, MS
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Theo Heller, MD
Professor
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Louis Y. Korman, MD
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Bethesda, Maryland, United States
Jeremy L. Davis, MD (he/him/his)
Professor of Surgery
Division of Surgical Oncology,
Department of Surgery,
University of Maryland School of Medicine
Baltimore, Maryland, United States
Rachael E. Belcher, MD (she/her/hers)
Research Fellow
University of Maryland School of Medicine
Baltimore, Maryland, United States
Hereditary diffuse gastric cancer is commonly caused by germline CDH1 loss-of-function variants. Individuals with pathogenic or likely pathogenic (P/LP) CDH1 variants are typically advised to undergo prophylactic total gastrectomy (PTG), even though most patients harbor indolent, early-stage signet ring cell (SRC) lesions. Endoscopic surveillance has emerged as an alternative management strategy. The primary goal of this study was to evaluate the outcomes of endoscopic surveillance.
Methods:
Patients with CDH1 P/LP variants who enrolled in a longitudinal cohort study and underwent surveillance esophagogastroduodenoscopy (EGD) were included. Non-targeted (random) mucosal biopsies were performed at all EGDs, and targeted biopsies were obtained using high-definition white light and narrow band imaging. Bivariate analyses and Kaplan–Meier survival estimates, including SRC-positive versus SRC-negative subgroups, were performed.
Results:
From January 2017 to September 2023, a total of 315 patients underwent 677 EGDs (median 2 per patient; IQR 1–3). Following initial endoscopy, 175 (55.6%) of 315 individuals elected to continue cancer surveillance with two or more endoscopies. Median follow up was 52.9 months (IQR 42.9-67). 107 (34%) proceeded to PTG, with a median time from initial EGD to PTG of 5.7 months (IQR 2.7-13.9). Targeted biopsies were performed in 72.7% of EGDs. 48% (84/175) of patients who underwent two or more endoscopies were diagnosed with SRC carcinoma. SRC yield was 25.1% for non-targeted, 1.6% for targeted, and 5.3% for combined biopsies. For patients undergoing active surveillance, the overall survival was 100% at 1 year, 99.4% at 3 years, and 97.1% at 5 years. Gastric cancer–specific survival was 100%. Survival did not differ by management strategy (p=0.77) or SRC detection (p=0.36).
Conclusions:
Endoscopic surveillance in CDH1 carriers was associated with excellent disease-specific survival, independent of SRC detection. With median follow-up approaching 5 years, these data support surveillance as a safe alternative to PTG in selected patients.