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Peer-reviewedCC BY-NC-ND 4.0Histopathology

The prognostic value of tumour budding for survival in stage II and III colorectal cancer: a systematic review and meta‐analysis

  • Yao Shu1
  • Heng Zhang1
  • Alessandro Lugli2
  • Femke Simmer1
  • Iris D. Nagtegaal1
  1. 1Department of Pathology Radboud University Medical Center Nijmegen Gelderland The Netherlands
  2. 2Institute for Tissue Medicine and Pathology University of Bern Bern Switzerland
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Abstract

Aims: Tumour budding (TB) has been recognized as an additional prognostic factor in the TNM (2017) and WHO (2019) classification systems. However, its prognostic impact in stages II and III colorectal cancer (CRC) remains inconsistently defined. This study aims to systematically evaluate the prognostic value of high‐grade TB in stage II–III CRC.

Methods and results: A systematic search of PubMed, Embase and Cochrane Library was conducted to identify studies reporting the association between high‐grade TB and survival outcomes in stage II–III CRC. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS), overall survival (OS) and cancer‐specific survival (CSS) were calculated using random‐effects models.

A total of 43 studies involving 17,831 patients were included. Univariable analysis showed that high‐grade TB was significantly associated with worse DFS (HR 2.53, 95% CI 2.14–3.00), OS (HR 2.40, 95% CI 1.69–3.42) and CSS (HR 3.37, 95% CI 2.19–5.19). Multivariable analysis confirmed the independent prognostic value of high‐grade TB for all three outcomes. Subgroup analysis stratified by TNM stage revealed that high‐grade TB consistently predicted adverse outcomes in both stage II and stage III disease.

Conclusions: This study confirms that high‐grade TB is an independent prognostic factor in stage II–III CRC, consistently associated with worse DFS, OS and CSS. Incorporating TB into routine histopathological assessment may improve risk stratification and help identify high‐risk patients, although its role in guiding therapeutic decisions requires further prospective validation.

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Cite

BibTeXRIS
BibTeX
@article{shu2026prognostic,
  title = {{The prognostic value of tumour budding for survival in stage II and III colorectal cancer: a systematic review and meta‐analysis}},
  author = {Yao Shu and Heng Zhang and Alessandro Lugli and Femke Simmer and Iris D. Nagtegaal},
  journal = {Histopathology},
  year = {2026},
  month = jun,
  doi = {10.1111/his.70225},
  url = {https://doi.org/10.1111/his.70225},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - The prognostic value of tumour budding for survival in stage II and III colorectal cancer: a systematic review and meta‐analysis
AU  - Yao Shu
AU  - Heng Zhang
AU  - Alessandro Lugli
AU  - Femke Simmer
AU  - Iris D. Nagtegaal
PY  - 2026
DA  - 2026/06/20
JO  - Histopathology
DO  - 10.1111/his.70225
UR  - https://doi.org/10.1111/his.70225
AB  - Aims: Tumour budding (TB) has been recognized as an additional prognostic factor in the TNM (2017) and WHO (2019) classification systems. However, its prognostic impact in stages II and III colorectal cancer (CRC) remains inconsistently defined. This study aims to systematically evaluate the prognostic value of high‐grade TB in stage II–III CRC.  Methods and results: A systematic search of PubMed, Embase and Cochrane Library was conducted to identify studies reporting the association between high‐grade TB and survival outcomes in stage II–III CRC. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS), overall survival (OS) and cancer‐specific survival (CSS) were calculated using random‐effects models.  A total of 43 studies involving 17,831 patients were included. Univariable analysis showed that high‐grade TB was significantly associated with worse DFS (HR 2.53, 95% CI 2.14–3.00), OS (HR 2.40, 95% CI 1.69–3.42) and CSS (HR 3.37, 95% CI 2.19–5.19). Multivariable analysis confirmed the independent prognostic value of high‐grade TB for all three outcomes. Subgroup analysis stratified by TNM stage revealed that high‐grade TB consistently predicted adverse outcomes in both stage II and stage III disease.  Conclusions: This study confirms that high‐grade TB is an independent prognostic factor in stage II–III CRC, consistently associated with worse DFS, OS and CSS. Incorporating TB into routine histopathological assessment may improve risk stratification and help identify high‐risk patients, although its role in guiding therapeutic decisions requires further prospective validation.
SN  - 0309-0167
SN  - 1365-2559
ER  -