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

Abstract

The epidemiology of gastric cancer is changing in Western populations. Population growth and ageing are projected to increase absolute case numbers despite declining age-standardised incidence, while historical registry data suggest changes in the relative contribution of diffuse-type disease, subject to period and coding effects. These trends give renewed urgency to understanding a cancer whose biology challenges established care. This narrative minireview examines the resulting gaps in prevention, diagnosis, staging and treatment of sporadic diffuse-type gastric cancer. No validated precursor sequence supports subtype-specific surveillance, and infiltrative growth complicates detection. Treatment presents a further mismatch: Enrichment for genomically stable biology and lower frequencies of human epidermal growth factor receptor 2 positivity and mismatch-repair deficiency restrict some therapeutic opportunities, while variable programmed death-ligand 1 expression requires individual assessment. Systemic trials have transformed gastric cancer care, but their heterogeneous populations and exploratory histological analyses leave diffuse-specific benefit incompletely defined. Peritoneal tropism compounds these difficulties. DRAGON-01 supports an intraperitoneal paclitaxel-containing strategy in China, with port morbidity and uncertain Western applicability; PERISCOPE II found greater morbidity without survival benefit from early operative treatment. Progress therefore requires better precursor identification and staging, together with systemic-treatment research that integrates histology and biomarkers and tests regional chemotherapy separately from surgery.

Keywords: Diffuse-type gastric cancer; Poorly cohesive carcinoma; Gastric carcinogenesis; Gastric atrophy; Molecular biomarkers; Systemic therapy; Immunotherapy; Peritoneal metastasis; Staging laparoscopy

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.