A comparative study of endoscopic surveillance in hereditary diffuse gastric cancer according to CDH1 mutation status

Abstract

Background and aims Hereditary Diffuse Gastric Cancer (HDGC) accounts for 1% of gastric cancer cases. For patients with a germline CDH1 mutation, risk-reducing gastrectomy is recommended. However, for those delaying surgery or families with no causative mutation identified, regular endoscopy is advised. This study aimed to determine the yield of signet ring cell carcinoma (SRCC) foci in individuals with a CDH1 pathogenic variant compared to those without and how this varies with successive endoscopies. Methods Patients fulfilling HDGC criteria were recruited to a prospective longitudinal cohort study. Endoscopy was performed according to a strict protocol with visual inspection followed by focal lesion and random biopsies, to detect foci of SRCC. Survival analysis determined progression to finding of SRCC according to CDH1 mutation status. EORTC-QLQ-C30 and SF-36 questionnaires assessed quality-of-life at pre-surveillance and each endoscopy. Results 85 individuals fulfilling HDGC criteria underwent 201 endoscopies. 54 (63.5%) tested positive for CDH1 mutation. SRCC yield was 61.1% in CDH1 mutation carriers compared to 9.7% in non-carriers, and mutation positive patients had a 10-fold risk of SRCC on endoscopy compared to those with no mutation detected (p<0.0005). Yield of SRCC decreased substantially with subsequent endoscopies. Surveillance was associated with improved psychological health. Conclusions SRCC foci are prevalent in CDH1 mutation carriers and can be detected at endoscopy using a standardised, multiple biopsy protocol. Decreasing yield over time suggests that the frequency of endoscopy might be reduced. For patients with no CDH1 pathogenic variant detected, the cost:benefit ratio needs to be assessed in view of the low yield.