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 among patients undergoing surgery for the prevention of gastric cancer.

Methods: This was a retrospective analysis of 150 individuals with germline CDH1 P/LP variants who underwent PTG 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 PTG with the aid of a multidisciplinary enhanced recovery after surgery (ERAS) pathway. This study demonstrated that acute major morbidity (Clavien-Dindo grade of ≥3) was low (17/150 [11.3%]) and that the most common complication was anastomotic leak (11/150 [7.3%]) in the setting of a comprehensive preoperative and postoperative care pathway. Nearly all gastrectomy specimens (132/150 [88.0%]) 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: PTG can be performed with low surgical morbidity in a high-volume center. The delivery of patient-centered care by a multidisciplinary team and the application of an ERAS pathway may improve short-term outcomes. However, interventions that can reduce chronic morbidity associated with total gastrectomy warrant further study.