Tumor budding as a predictive factor of lymph node metastases and survival in endometrial cancer patients: A systematic review and meta-analysis.

BACKGROUND

Tumor budding (TB), defined as isolated single cells or small clusters at the invasive front, has emerged as an adverse prognostic marker in several solid tumors. Its prognostic value in endometrial carcinoma (EC), however, remains uncertain.

METHODS

We conducted a systematic review and meta-analysis (PROSPERO registration: CRD420251066731) of studies evaluating the association between TB and survival outcomes and lymph node positivity in EC. Comprehensive searches of CENTRAL, MEDLINE, PubMed, Scopus, and Google Scholar identified eligible observational studies.

RESULTS

Ten studies comprising 1307 patients were included. TB was significantly associated with reduced progression-free survival (hazard ratio [HR] 2.44, 95% confidence interval [CI] 1.53-3.89) and overall survival (HR 1.89, 95% CI 1.21-2.96). Sensitivity analyses revealed attenuation of these associations after accounting for small-study effects, although trim-and-fill estimates remained statistically significant for progression-free survival. Evidence for an association between TB and lymph node metastasis was inconsistent and not robust after correction for potential bias.

CONCLUSION

Tumor budding is associated with adverse survival outcomes in EC, highlighting its potential as a histopathological biomarker of aggressive disease. However, heterogeneity in assessment methods and limited integration with molecular classification constrain its current clinical applicability. Standardized evaluation and validation in large, molecularly stratified cohorts are essential to establish TB as an independent prognostic factor and to define its role in guiding adjuvant treatment decisions.