Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis

Robert Schoeneich; Rishi R Patel; Bohae R Lee; Paolo Disano; Matthew T Gao; Madeline VanDerGraaf; Matthew Gosse; Rami El Abiad; Avraham Levin; Chandrikha Chandrasekharan; Hisakazu Hoshi; Andrew M Bellizzi; Naomi H Fei; Udhayvir S Grewal

doi:10.1097/COC.0000000000001350

Back

Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis

Journal article

Peer reviewed

Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis

Robert Schoeneich, Rishi R Patel, Bohae R Lee, Paolo Disano, Matthew T Gao, Madeline VanDerGraaf, Matthew Gosse, Rami El Abiad, Avraham Levin, Chandrikha Chandrasekharan, …

American journal of clinical oncology

06/30/2026

DOI: 10.1097/COC.0000000000001350

PMID: 42397948

View Online

Abstract

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.

genetic counseling

diffuse hereditary gastric cancer

CDH1

prophylatic total gastrectomy

Details

Title: Subtitle: Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis
Creators: Robert Schoeneich - University of Iowa
Rishi R Patel - University Hospitals of Cleveland
Bohae R Lee - University of Iowa
Paolo Disano - University of Iowa
Matthew T Gao - University of Iowa
Madeline VanDerGraaf - University of Iowa
Matthew Gosse - Department of Pathology
Rami El Abiad - Divisions of Gastroenterology and Hepatology
Avraham Levin - Divisions of Gastroenterology and Hepatology
Chandrikha Chandrasekharan - The University of Texas MD Anderson Cancer Center
Hisakazu Hoshi - Department of Surgery
Andrew M Bellizzi - Department of Pathology
Naomi H Fei - University of Iowa
Udhayvir S Grewal - Emory University
Resource Type: Journal article
Publication Details: American journal of clinical oncology
DOI: 10.1097/COC.0000000000001350
PMID: 42397948
ISSN: 1537-453X
eISSN: 1537-453X
Publisher: Wolters Kluwer
Language: English
Electronic publication date: 06/30/2026
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Gastroenterology and Hepatology; Pathology; Surgery; Internal Medicine
Record Identifier: 9985179238202771

Metrics

1 Record Views