Decreasing diffuse gastric cancer risk in individuals with germline CDH1 pathogenic variants. What about prophylactic total gastrectomy?

We read with interest the recent original paper by Benusiglio et al.1 The authors reported a series of 20 individuals at high risk for diffuse gastric cancer (DGC) with a documented germline CDH1 pathogenic variant. These individuals refused or were not eligible for prophylactic total gastrectomy (PTG) and opted for endoscopic surveillance every 6 or 12 months, in accordance with the Cambridge protocol. pT1a signet-ring cell carcinoma (SRCC) foci were identified in 6/20 patients during a mean follow-up of 62 months. However, none of these subjects developed an advanced DGC beyond >pT1a. Other studies reported similar results, but with a short follow-up.2 3

In 2015, Hansford et al reported that in individuals fulfilling the International Gastric Cancer Linkage Consortium 2010 criteria with germline CDH1 pathogenic variants, the cumulative lifetime gastric cancer (GC) risk at 80 years of age was…