Long-term Endoscopic Surveillance in Hereditary Diffuse Gastric Cancer Syndrome

Hereditary Diffuse Gastric Cancer (HDGC) syndrome arises from a germline variant in CDH1 and is characterized by a high risk of gastric signet-ring cell carcinoma. Total gastrectomy is the most definitive strategy for cancer risk reduction but carries high morbidity. Endoscopic surveillance is an alternative, but there are limited data on long-term outcomes with this approach. We sought to define the outcomes of long-term endoscopic surveillance in a HDGC cohort. We retrospectively analyzed the demographic, clinical, endoscopic, and histopathological records of 102 patients with pathogenic or likely pathogenic (P/LP) CDH1 variants at Massachusetts General Hospital. We defined short-term endoscopic surveillance as less than 3 years and long-term surveillance as 3 years or longer. The HDGC cohort included 68 female and 34 male patients, with a mean age at diagnosis of 42.1 years. Thirty-four patients opted for immediate risk-reducing gastrectomy and 40 pursued endoscopic surveillance. 20 individuals comprised the short-term surveillance group (median follow-up 1.4 years) and there were 20 individuals in the long-term surveillance group (median follow-up 5.1 years). There were two cases of advanced gastric cancer (>T1a) identified, and both occurred in the long-term surveillance group. Both were managed with gastrectomy and remain cancer-free. There were no gastric cancer-related deaths. In this series, long-term endoscopic surveillance identified advanced gastric cancers in HDGC at treatable stages without any gastric cancer-related mortality. These findings suggest endoscopic surveillance may be a reasonable long-term strategy in HDGC for select individuals.