Prophylactic total gastrectomy in germline CDH1 carriers: results across 25 years from a systematic review and meta-analysis.

CDH1

Germline pathogenic CDH1 variants conferring a high risk of diffuse gastric cancer, for which prophylactic total gastrectomy is a risk-reducing strategy

Prophylactic total gastrectomy (PTG) is a risk-reducing strategy considered in people at high risk of diffuse gastric cancer associated with a germline pathogenic CDH1 variant. This systematic review (PubMed, Scopus), registered in PROSPERO, retained 21 of 302 identified studies, including 967 CDH1 carriers, and pooled the data with a random-effects generalised linear mixed model, with estimates calculated over three periods (2001-2010, 2011-2020 and 2021-2025). PTG was performed in 62.9% of carriers; in postoperative specimens, advanced diffuse gastric cancer (>pT1a) was detected in 1.1% and ≤pT1a lesions in 79%, and 58.9% of gastrectomies were reported from North America. The pooled proportion of gastrectomies fell from 83.2% (95% CI 61.0-94.0) in 2001-2010 to 71.0% (59.0-80.7) in 2011-2020 and 67.5% (48.9-81.8) in 2021-2025 (p for trend = 0.12), which the authors relate to recent genetic analyses reporting a lower diffuse gastric cancer risk in CDH1 carriers and to better endoscopic detection of early lesions.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The most useful figure for counselling is the make-up of the surgical specimens: 79% of lesions ≤pT1a and only 1.1% advanced cancers, which documents both how common early lesions are and how rare advanced cancers are in operated carriers. The text concludes that indications have been steadily decreasing, but the trend is not significant (p = 0.12) and the intervals overlap widely (61.0-94.0% in 2001-2010, 48.9-81.8% in 2021-2025): this is a signal, not a demonstration. The abstract reports neither a comparison with surveillance nor morbidity data, and attributing the decline to new risk estimates and endoscopy remains the authors' interpretation, so these data inform counselling without settling an individual choice.

Analysis by Dr Thibaut Benquey