Expert endoscopic surveillance in <i>CDH1</i> pathogenic variant carriers seems safe, even after positive (pT1a) biopsies

Surveillance is increasingly considered an alternative to prophylactic total gastrectomy in asymptomatic carriers of <i>CDH1</i> pathogenic variants. There are three main reasons for this paradigm shift: (1) decreasing penetrance estimates for signet ring cell gastric cancer based on large, unselected case series, (2) increasing evidence for the indolent nature of pT1a (intramucosal) lesions and (3) recent improvements in the performances of endoscopic surveillance. We report on 20 carriers undergoing long-term surveillance with an annual upper gastrointestinal gastroscopy per Cambridge protocol. There were 8 women and 12 men, with a median age of 42 years (range 19-70). Thirteen (65%) carriers had a family history of gastric cancer. Mean follow-up duration was 62 months (range 17-128). The total number of endoscopies was 95, with a mean and median of 4.75 and 4, respectively. Ten pT1a signet ring cell carcinoma foci were identified in six patients; nine through random and one through targeted biopsies. There were no atypias or mitoses. All patients pursued surveillance regardless of biopsies. None developed aggressive (>pT1a) cancer. The longest follow-up after a positive biopsy was 82 months. Survival for the whole cohort was 100%. In conclusion, annual expert endoscopic surveillance appears safe, and pT1a lesions should not be seen as a formal indication for PTG. We emphasise the importance of providing patients with balanced, individualised and up-to-date information.