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Prognostic Impact of Tumor Budding in Squamous Cell Carcinoma of the Lung: A Systematic Review and Meta-analysis.

INTRODUCTION
Tumor budding is an established prognostic factor in various solid tumors, including colorectal cancers and oral squamous cell carcinomas. However, its role is unclear and needs to be defined for squamous cell carcinoma of the lung (LSCC). Hence, we conducted a systematic review and meta-analysis investigating the prognostic role of tumor budding in LSCC.


METHODS
PubMed, Embase, and Scopus were searched for peer-reviewed literature investigating the association between tumor budding and survival outcomes or clinicopathologic variables in LSCC. The primary outcomes were pooled estimates for overall and recurrence-free survival with Hazard Ratio (HR) as the effect measure. The association between tumor budding and clinicopathologic parameters was also investigated.


RESULTS
Of 243 studies, nine were included comprising 2 546 patients. An increased risk of death [HR 1.76 95% CI 1.50-2.05 p < 0.00001] and recurrence [HR, 1.37; 95% CI, 1.12-1.68; p = 0.003] was evident in patients with high-grade tumor budding. Sensitivity and subgroup analyses revealed consistent results. Pathological stage-II, lymph node metastasis, lymphovascular, and pleural invasion were associated with high-grade tumor budding.


CONCLUSION
Tumor budding is a new and promising prognostic factor in patients with LSCC. However, pervasive heterogeneity and publication bias reduces the credibility of these findings and the applicability of tumor budding in clinical practice. Future studies are required to standardize reporting on tumor budding in LSCC.