Predictors of early cancer burden in CDH1 pathogenic variant carriers: a UK single-centre cohort study.

Germline CDH1 variants

Hereditary diffuse gastric cancer with germline CDH1 variants carries a high risk of signet ring cell carcinoma (SRCC), with limited data to choose between endoscopic surveillance and prophylactic total gastrectomy. This single-centre cohort study (Cambridge, 2005-2024) analysed 53 patients who underwent surgery after endoscopic evaluation and 93 under longitudinal surveillance. In the surgical cohort, 89% had early-stage cancer (pT1aN0M0), with SRCC foci ranging from 0 to 273 (median 14). The number of positive targeted and random biopsies independently predicted SRCC burden at gastrectomy (P < 0.001), whereas age, CDH1 variant type and number of affected relatives were not. Under surveillance, positive biopsy counts remained stable over time, supporting the safety of endoscopic monitoring and extended intervals.

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

These data offer tangible support for deferring prophylactic total gastrectomy in CDH1 carriers with few lesions, a major and irreversible operation. The correlation between systematic biopsies and final tumour burden reinforces the value of endoscopic surveillance under the Cambridge protocol. The prognostic significance of a high SRCC burden must be clarified before generalising these extended intervals.

Analysis by Dr Thibaut Benquey