Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1...

Hereditary diffuse gastric cancer (HDGC) due to germline CDH1 pathogenic or likely pathogenic (P/LP) variants has traditionally been managed with prophylactic total gastrectomy (PTG), although contemporary data suggest a lower and more heterogeneous cancer risk. Real-world management patterns remain incompletely defined.

We conducted a retrospective, single-center cohort study of adult patients with germline CDH1 P/LP variants managed between 2011 and 2024. Patients were categorized as undergoing PTG within 1 year of diagnosis or deferring surgery with endoscopic surveillance (ES). Primary outcomes included the detection of signet ring cell carcinoma (SRCC) and invasive gastric cancer.

A total of 27 patients were identified (median age: 48 y; 81.5% female). Eight (29.6%) underwent early PTG, while 18 (66.7%) initially deferred surgery; 1 presented with de novo metastatic gastric cancer. Among PTG patients, 7 of 8 (87.5%) had Tis/T1a SRCC, and none had nodal involvement. Among those deferring PTG, surveillance was heterogeneous: 8 (44.4%) underwent structured ES, 6 (33.3%) had a single endoscopy, and 4 (22.2%) had no surveillance. Within structured ES, 1 patient (12.5%) developed invasive T2 disease, while the others had Tis/T1a SRCC or normal histology. Delayed gastrectomy (27.8%) revealed predominantly T1a SRCC without nodal involvement.

Most detected lesions were early-stage and node-negative, and delayed gastrectomy did not appear to compromise pathologic outcomes in selected patients. However, invasive progression during surveillance underscores that ES is not without risk. These findings support a risk-adapted, patient-centered approach to CDH1 management with emphasis on structured surveillance and shared decision-making.