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

Area of Science:

• Genetics
• Oncology
• Gastroenterology

Background:

• Hereditary diffuse gastric cancer (HDGC) is linked to CDH1 variants.
• Prophylactic total gastrectomy (PTG) is the traditional management.
• Cancer risk in CDH1 variant carriers is lower and more varied than previously thought.

Purpose of the Study:

• To evaluate real-world management patterns for patients with germline CDH1 pathogenic or likely pathogenic (P/LP) variants.
• To compare outcomes of prophylactic total gastrectomy (PTG) versus endoscopic surveillance (ES).
• To assess the risk of gastric cancer progression during surveillance.

Main Methods:

• Retrospective, single-center cohort study of adult patients with germline CDH1 P/LP variants (2011-2024).
• Patients categorized into early PTG or deferred surgery with ES groups.
• Primary outcomes: detection of signet ring cell carcinoma (SRCC) and invasive gastric cancer.

Main Results:

• 27 patients analyzed; 8 underwent early PTG, 18 deferred surgery.
• Early PTG patients mostly had Tis/T1a SRCC with no nodal involvement.
• Among those deferring PTG, surveillance varied; structured ES detected early-stage disease, but one patient progressed to T2 invasive disease.
• Delayed gastrectomy revealed predominantly T1a SRCC without nodal involvement.

Conclusions:

• Most detected gastric lesions in CDH1 variant carriers are early-stage and node-negative.
• Delayed gastrectomy appears safe for selected patients.
• Endoscopic surveillance carries risks of invasive progression, necessitating structured approaches and shared decision-making.