{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:33:44Z","timestamp":1783038824901,"version":"3.54.6"},"reference-count":37,"publisher":"Harborside Press, LLC","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>Gastric cancer is a significant global health concern, with <jats:italic>CDH1<\/jats:italic>-associated gastric cancer representing a small but important subset of cases. Historically, individuals with <jats:italic>CDH1<\/jats:italic> pathogenic germline variants were advised to undergo prophylactic total gastrectomy due to the high reported risk of gastric cancer and the limited sensitivity of upper endoscopy in detecting signet ring cell carcinoma (SRCC). However, emerging data suggest that the cumulative lifetime risk of advanced gastric cancer among <jats:italic>CDH1<\/jats:italic> germline pathogenic variant carriers is lower than previously thought, and early-stage SRCC detected on endoscopy does not necessarily indicate imminent\u2014or even eventual\u2014progression to advanced cancer. The near-universal presence of T1a SRCC in gastrectomy specimens from asymptomatic <jats:italic>CDH1<\/jats:italic> pathogenic variant carriers calls into question the reflexive recommendation for gastrectomy, including upon detection of SRCC during surveillance. Furthermore, the morbidity and quality-of-life impact associated with total gastrectomy require careful consideration. Active endoscopic surveillance has shown promise as an alternative management strategy for gastrectomy in patients lacking indicators of &gt;T1a SRCC, though current data are limited by short follow-up periods and selection bias. This review synthesizes recent findings on the natural history of <jats:italic>CDH1<\/jats:italic>-associated gastric cancer and evaluates the risks and benefits of gastrectomy versus active endoscopic surveillance, with the goal of helping clinicians provide personalized and evidence-based recommendations for patients with <jats:italic>CDH1<\/jats:italic> pathogenic variants.<\/jats:p>","DOI":"10.6004\/jnccn.2025.7006","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T12:46:38Z","timestamp":1744202798000},"source":"Crossref","is-referenced-by-count":5,"title":["Advancing the Evaluation and Management of CDH1-Associated Gastric Cancer"],"prefix":"10.6004","volume":"23","author":[{"given":"Benjamin A.","family":"Lerner","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Yale University, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Burke","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Kupfer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryson W.","family":"Katona","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Grady","sequence":"additional","affiliation":[{"name":"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, and Gastroenterology Division, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jewel J.","family":"Samadder","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Yurgelun","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Wisconsin, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Moreno Prats","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory E.","family":"Idos","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska, Lincoln, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AnnMarie","family":"Kieber-Emmons","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Llor","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Yale University, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","article-title":"Global cancer observatory: cancer today.","author":"Ferlay JE","unstructured":"Ferlay JE, Lam F, Laversanne M,  Global cancer observatory: cancer today. 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