Lessons learned from 150 total gastrectomies for prevention of cancer

Background: Prophylactic total gastrectomy (PTG) is performed in carriers of CDH1 pathogenic and likely pathogenic (P/LP) variants and is becoming more frequent with broader use of germline genetic testing. There is an unmet need to standardize care and enhance outcomes in patients undergoing surgery for prevention of gastric cancer.

Methods: We performed a retrospective analysis of 150 individuals with germline CDH1 P/LP variants who underwent prophylactic total gastrectomy as part of a prospective natural history study from October 2017 to May 2023. All individuals received multidisciplinary, protocolized care before and after total gastrectomy.

Results: A total of 150 asymptomatic patients with germline CDH1 P/LP variants underwent prophylactic total gastrectomy with the aid of a multidisciplinary enhanced recovery after surgery pathway. We demonstrated that acute major morbidity (Clavien-Dindo Grade ≥3) was low (11.3%, 17/150) and the most common complication was anastomotic leak (7.3%, 11/150) in the setting of a comprehensive preoperative and postoperative care pathway. Nearly all (88%, 132/150) gastrectomy specimens harbored occult signet ring cell lesions on final pathology. There were no gastric cancer recurrences or gastric cancer-related deaths during the study period with a median overall follow-up of 36 months (IQR 24-48) from gastrectomy.

Conclusion: Prophylactic total gastrectomy can be performed with low surgical morbidity in a high-volume center. The delivery of patient-centered care by a multidisciplinary team and application of an enhanced recovery after surgery pathway may improve short-term outcomes. Interventions that can ameliorate the chronic morbidity associated with total gastrectomy, however, warrant further study.