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. Though 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 CRC cohort. 379 patients with resected Stage I-IV colorectal cancer were entered into the study. Tumor budding was scored by two pathologists according to the ITBCC recommendations on hematoxylin and eosin-stained slides and scored as BD1 (low-), BD2 (intermediate-) 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 (HR 1.023 (95%CI: 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.