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Review
. 2025 May 27;4(9):100713.
doi: 10.1016/j.gastha.2025.100713. eCollection 2025.

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

Heng Zhang  1 , Femke Simmer  1 , Alessandro Lugli  2 , Iris D Nagtegaal  1
Affiliations
Review

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

Heng Zhang et al. Gastro Hep Adv. .

Abstract

Background and aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Local Recurrence; Lymph Node Metastasis; Tumor Budding; pT1 Colorectal Cancer.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Flow chart of selection process.
Figure 2
Figure 2
Forest plot with RR of risk of TB in relation to LNM.
Figure 3
Figure 3
Forest plot with RR of risk of TB in relation to local RE. Local RE, local recurrence.
Figure A1
Figure A1
Sensitivity analysis between TB and LNM.
Figure A2
Figure A2
Sensitivity analysis between TB and local RE. Local RE, local recurrence.
Figure A3
Figure A3
Funnel plot between tumor TB and LNM.
Figure A4
Figure A4
Funnel plot obtained with the trim and fill method for the analysis of TB and LNM.
Figure A5
Figure A5
Funnel plot between TB and local RE. Local RE, local recurrence.
See this image and copyright information in PMC

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