Tumor Budding as a Risk Factor for Lymph Node Metastasis and Local Recurrence in pT1 Colorectal Cancer: A Systematic...

Implementation of population screening programs resulted in an increase in early colorectal cancer (CRC, pT1). For these small CRC, endoscopic local resection is the preferred treatment. However, the presence of lymph node metastasis (LNM) and risk of local recurrence might require additional surgery. Tumor budding (TB) is a well-known biomarker for adverse outcomes in pT1 CRC. This study aims to further explore the relationship between TB and in pT1 CRC and to clarify the relationship between TB and local recurrence, to provide more strategies for the selection of surgical treatment.

A systematic review was conducted using the MEDLINE and EMBASE databases to investigate the relationship between TB and LNM and local recurrence in pT1 CRC. Meta-analysis based on a random-effects model was performed to evaluate the relationship between TB and these 2 factors.

A total of 57 observational studies were included in the meta-analysis, with a total of 24,956 patients. High-grade TB was significantly associated with both LNM (risk ratio (RR) = 4.04, 95% confidence interval (CI), 3.52-4.64, I² = 56.11%, P < .001) and local recurrence (RR = 2.35, 95% CI, 1.21-4.54, I² = 26.18%, P = .01). Sensitivity analysis confirmed the robustness of our pooled results. Subgroup analysis also explored possible sources of heterogeneity. For LNM, geographical location (Asia: RR = 4.22, 95% CI, 3.64-4.89; Others: RR = 2.72, 95% CI, 2.08-3.57, P = .01) and year of publication (<2015: RR = 4.96, 95% CI, 4.01-6.15; ≥2015: RR = 3.58, 95% CI, 2.99-4.29, P = .02) showed significant differences in the subgroup analysis. We cannot rule out publication bias for LNM risk.

Our findings confirm that TB is a strong predictor of local recurrence, but in particular of LNM in pT1 CRC and offers effective guidance for selecting further surgical treatment strategies.