Sporadic diffuse gastric cancer in Western populations and the mismatch between tumour biology and clinical care

Core Tip

Core Tip: Population growth and ageing may increase Western gastric cancer case numbers, while historical registry data suggest a changing relative contribution of diffuse disease. Sporadic diffuse cancer lacks a validated precursor and can evade diagnosis. Its enrichment for genomically stable biology, lower human epidermal growth factor receptor 2 positivity and less frequent mismatch-repair deficiency complicate systemic-treatment selection, while programmed death-ligand 1 expression remains variable. Histological subgroup analyses incompletely define treatment benefit, making individual biomarker testing and better therapeutic evidence essential. Peritoneal tropism adds a further challenge, requiring regional chemotherapy and surgery to be tested separately alongside systemic care. These connected gaps demand a subtype-specific response to the changing burden.