Cancer surveillance as an alternative to prophylactic total gastrectomy in hereditary diffuse gastric cancer: a prospective cohort study

• Published in: The lancet oncology 2023-04, Vol.24 (4), p.383-391
• Main Authors: Asif, Bilal, Sarvestani, Amber Leila, Gamble, Lauren A, Samaranayake, Sarah G, Famiglietti, Amber L, Fasaye, Grace-Ann, Quezado, Martha, Miettinen, Markku, Korman, Louis, Koh, Christopher, Heller, Theo, Davis, Jeremy L
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - surgery; Anesthesia; Asymptomatic; Biopsy; Breast cancer; Carcinoma, Signet Ring Cell - diagnosis; Carcinoma, Signet Ring Cell - epidemiology; Carcinoma, Signet Ring Cell - genetics; Cerebrovascular diseases; Cohort analysis; E-cadherin; Endoscopy; Family medical history; Female; Gastrectomy; Gastrectomy - adverse effects; Gastric cancer; Gastrointestinal surgery; Genetic Predisposition to Disease; Germ-Line Mutation; Health surveillance; Humans; Invasiveness; Male; Medical prognosis; Medical research; Metastases; Morbidity; Natural history; Patient safety; Phenotypes; Prospective Studies; Stomach Neoplasms - diagnosis; Stomach Neoplasms - epidemiology; Stomach Neoplasms - genetics; Surgery
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(23)00057-8

Loss of function variants in CDH1 are the most frequent cause of hereditary diffuse gastric cancer. Endoscopy is regarded as insufficient for early detection due to the infiltrative phenotype of diffuse-type cancers. Microscopic foci of invasive signet ring cells are pathognomonic of CDH1 and precede development of diffuse gastric cancer. We aimed to assess the safety and effectiveness of endoscopy for cancer interception in individuals with germline CDH1 variants, particularly in those who declined prophylactic total gastrectomy. In this prospective cohort study, we included asymptomatic patients aged 2 years or older with pathogenic or likely pathogenic germline CDH1 variants who underwent endoscopic screening and surveillance at the National Institutes of Health (Bethesda, MD, USA) as part of a natural history study of hereditary gastric cancers (NCT03030404). Endoscopy was done with non-targeted biopsies and one or more targeted biopsy and assessment of focal lesions. Endoscopy findings, pathological data, personal and family cancer history, and demographics were recorded. Procedural morbidity, gastric cancer detection by endoscopy and gastrectomy, and cancer-specific events were assessed. Screening was defined as the initial endoscopy and all subsequent endoscopies were considered surveillance; follow-up endoscopy was at 6 to 12 months. The primary aim was to determine effectiveness of endoscopic surveillance for detection of gastric signet ring cell carcinoma. Between Jan 25, 2017, and Dec 12, 2021, 270 patients (median age 46·6 years [IQR 36·5–59·8], 173 [64%] female participants, 97 [36%] male participants; 250 [93%] were non-Hispanic White, eight [3%] were multiracial, four [2%] were non-Hispanic Black, three [1%] were Hispanic, two [1%] were Asian, and one [