Background: Tumour budding (TB) is an established prognostic biomarker colorectal cancer reflecting an invasive growth pattern and associated with worse clinical outcomes. In gastroesophageal cancers, however, its role remains exploratory. This systematic review and meta-analysis build the existing evidence base to clarify the clinical relevance of TB as a biomarker in patients with gastric and oesophageal adenocarcinoma.
Methods: A systematic review was performed according to the PRISMA guidelines (PRISMA, 2020). The databases searched were CINAHL-Plus with full text (EBSCOhost), MEDLINE with full text (EBSCOhost), Pub Med and SCOPUS. We included all studies evaluating TB in gastric and oesophageal adenocarcinoma including all tumour stages, adenocarcinoma subtypes, and study designs that investigated the association of TB on outcomes (overall survival and relapse free survival) and histopathological features (T stage, nodal status, lymphovascular invasion and perineural invasion). The ROBINS-E risk of bias tool was used to evaluate the studies.
Results: The systematic review identified thirty-six eligible studies (n=7881 patients). Thirty studies evaluated tumour budding in gastric adenocarcinoma, five studies in oesopahgeal adenocarcinoma, and one study in gastro-oeosphageal junction adenocarcinoma. Eight studies on gastric adenocarcinoma used the definition of tumour budding based on the ITBCC guidelines of 2016. Thirteen studies evaluated the effect of high-grade tumour budding compared to low grade tumour budding on overall survival. The meta-analysis showed tumour budding was a statistically significant prognostic biomarker for overall survival in gastroesophageal adenocarcinoma with a pooled effect hazard ratio of 4.148 (95% CI 0.755-7.540, p value 0.021).
Conclusion: High tumour budding is significantly associated with poorer overall survival in patients with gastric adenocarcinoma compared to low tumour budding, supporting its role as a prognostic biomarker in this disease.