Validation of the International Tumor Budding Consensus Conference 2016 recommendations on tumor budding in stage I-IV colorectal cancer.

Tumor budding is a robust prognostic parameter in colorectal cancer and can be used as an additional factor to guide patient management. Although backed by large bodies of data, a standardized scoring method is essential for integrating tumor budding in reporting protocols. The International Tumor Budding Consensus Conference (ITBCC) 2016 has proposed such a scoring system. The aim of this study is to validate the ITBCC method of tumor budding assessment on a well-characterized colorectal cancer cohort. Three hundred seventy-nine patients with resected stage I-IV colorectal cancer were entered into the study. Tumor budding was scored by 2 pathologists according to the ITBCC recommendations on hematoxylin and eosin-stained slides and scored as BD1 (low grade), BD2 (intermediate grade), and BD3 (high grade). Analysis was performed using a 3-tier approach, a 2-tier approach (BD1 + 2 versus BD3) and budding as a continuous variable. High-grade tumor budding was associated with adverse clinicopathological features including higher pT, higher pN stage, and higher TNM stage (all P < .001) and poorer overall survival on univariate analysis (P = .0251 for BD1/2/3, P = .0106 for BD1 + 2 versus BD3, and P = .0195 for continuous scores; hazard ratio, 1.023 [95% confidence interval, 1.004-1.043 per bud]). In stage II cancers, BD3 was associated with poorer disease-free survival (P < .01). Tumor budding assessed by the method proposed by the ITBCC is applicable to colorectal cancer resection specimens and can be used for widespread reporting in routine.