S3105 Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis

Introduction: Gastric cancer (GC) is the fifth leading cause of cancer-related mortality worldwide. One to three percent of cases may result from hereditary cancer predisposition syndromes. Of these, pathogenic variants in CDH1 (resulting in diffuse gastric and lobular breast cancer syndrome) are among the most common. While prophylactic total gastrectomy (PTG) has long been considered a standard option, endoscopic surveillance (ES) is emerging as an effective organ-sparing approach. We sought to analyze care patterns and GC-related outcomes among these patients. Methods: In this single-center, institutional review board–approved, retrospective analysis, we identified and included patients with pathogenic or likely pathogenic (PLP) CDH1 germline variants who sought care at our institution (2011-2024). Patients harboring germline variants of uncertain significance in CDH1 were excluded. We abstracted data regarding baseline (patient and disease-focused) and treatment characteristics (PTG or ES). We then investigated outcomes for patients pursuing various care plans. Statistical analysis was performed using RStudio. Results: A total of 28 patients were included, of which, 8 (21%) underwent PTG (within 1 year of CDH1 testing, median time 5.5 months), 18 (64.3%) deferred PTG. Two patients (7.1%) were diagnosed with de novo metastatic disease. There was no significant difference in age at diagnosis (P = 0.40) or personal history of cancer (P = 0.84) between groups pursuing or deferring PTG. Of 8 patients who underwent PTG, 7 (87.5%) had a post-operative diagnosis of T1a/Tis signet ring cell carcinoma (SRCC), 1 (12.5%) had normal histology. Among 18 patients who deferred PTG, 9 (50%) underwent ES with at least 2 esophagogastroduodenoscopies, 7 (38.9%) had only 1 EGD, and 4 (22.2%) did not undergo any. After initial deferral, 5 of the 18 patients (27.8%) ultimately underwent PTG (median time to gastrectomy 41 months), with 4 (80%) with a post-operative diagnosis of T1a SRCC and 1 (20%) with normal histology. Among 9 patients who pursued ES (median follow-up 11 months), only 1 patient (11.1%) had developed invasive GC (T2). Conclusion: Among patients with PLP germline CDH1 variants, deferral of PTG was common. The incidence of invasive cancer among those who deferred PTG and/or pursued ES was low. Adherence to ES protocols was inconsistent in this real-world setting. Our findings underscore the practical challenges of ES and emphasize the need for refined strategies and biomarkers to guide decision-making in clinical practice.