P2027 - Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis

Robert Schoeneich, MD¹, Rishi R. Patel, BS², Bohae R. Lee, MD¹, Madeline VanDerGraaf, MS¹, Matthew Gosse, MD¹, Rami El Abiad, MD¹, Avraham Levin, MD¹, Chandrikha Chandrasekharan, MBBS³, Hisakazu Hoshi, MD¹, Andrew M. Bellizzi, MD¹, Naomi H. Fei, MD, MS², Udhayvir S. Grewal, MD¹
1University of Iowa Hospitals & Clinics, Iowa City, IA; 2University of Iowa Carver College of Medicine, Iowa City, IA; 3University of Texas MD Anderson Cancer Center, Houston, TX

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, IRB-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 (VUS) 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 one 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), one (12.5%) had normal histology. Among 18 patients who deferred PTG, nine (50%) underwent ES with at least two EGDs, 7 (38.9%) had only one EGD, and 4 (22.2%) did not undergo any. After initial deferral, five of the 18 patients (27.8%) ultimately underwent TG (median time to gastrectomy 41 months), with four (80%) with a post-operative diagnosis of T1a SRCC and one (20%) with normal histology. Among nine patients who pursued ES (median follow-up 11 months), only one patient (11.1%) had developed invasive GC (T2).

Discussion: 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.

Disclosures:
Robert Schoeneich indicated no relevant financial relationships.
Rishi Patel indicated no relevant financial relationships.
Bohae Lee indicated no relevant financial relationships.
Madeline VanDerGraaf indicated no relevant financial relationships.
Matthew Gosse indicated no relevant financial relationships.
Rami El Abiad indicated no relevant financial relationships.
Avraham Levin indicated no relevant financial relationships.
Chandrikha Chandrasekharan indicated no relevant financial relationships.
Hisakazu Hoshi indicated no relevant financial relationships.
Andrew Bellizzi: AstraZeneca (Any division) – Prepared a lecture on low/pan HER2.
Naomi Fei indicated no relevant financial relationships.
Udhayvir Grewal indicated no relevant financial relationships.

Robert Schoeneich, MD¹, Rishi R. Patel, BS², Bohae R. Lee, MD¹, Madeline VanDerGraaf, MS¹, Matthew Gosse, MD¹, Rami El Abiad, MD¹, Avraham Levin, MD¹, Chandrikha Chandrasekharan, MBBS³, Hisakazu Hoshi, MD¹, Andrew M. Bellizzi, MD¹, Naomi H. Fei, MD, MS², Udhayvir S. Grewal, MD¹. P2027 - Care Patterns and Gastric Cancer-Related Outcomes in Patients With Pathogenic/Likely Pathogenic Germline CDH1 Variants: A 14-Year Single-Center Analysis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.