Tumor budding is a strong predictor of disease-free survival in stage II colorectal cancer: Validation study based on the International Tumor Budding Consensus Conference (ITBCC) recommendations.

Abstract

594 Background: Tumor budding, defined as single tumor cells or small clusters of four or less tumor cells at the invasive front, has been shown to be a strong and independent prognostic factor in colorectal cancer (CRC). However, widespread reporting of tumor budding has been held back largely due to a lack of consensus on scoring methods. 23 experts from the United States, Canada, Japan and Europe participated at the International Tumor Budding Consensus Conference (ITBCC), held in April 2016 in Bern, Switzerland, and agreed on a set of recommendations for assessing and reporting tumor budding in CRC. The aim of this study was to validate the method proposed by ITBCC in the clinically relevant scenario of Stage II CRC. Methods: In 151 Stage II CRC patients, tumor budding was assessed on scanned H&E-stained slides in a single hot spot measuring 0.785mm2. Cutoffs as defined by ITBCC were used: Low (Bd1): 0-4 buds, intermediate (Bd2): 5-9 buds, high (Bd3): ≥ 10 buds. Statistical analysis for associations with clinicopathological features, disease free survival (DFS) and overall survival (OS) was performed. Results: The average number of buds/hotspot was 6.8 (median 5.0). 43.1% of cases were Bd1, 27.2% Bd2 and 29.8% Bd3. Tumor budding as a continuous variable was associated with extramural venous invasion (EMVI) (p = 0.05). Tumor budding was associated with poorer OS in univariate analysis (p = 0.0386, HR 1.048, 95%CI 1.002-1.095). For 3- and 5- year DFS, Bd3 was associated with significantly worse survival in comparison with Bd1/2 (p = 0.0031 and p = 0.0025, respectively). In multivariate analysis adjusting for pT, tumor grade and EMVI, tumor budding retained its adverse prognostic effect for DFS (p = 0.006, HR 3.293, 95%CI 1.66-6.53). Conclusions: This study provides promising data on tumor budding assessed by the ITBCC method in the Stage II scenario. Especially Bd3 shows a detrimental adverse impact on DFS in comparison to Bd1/Bd2. Based on the ITBCC, tumor budding has the potential to strongly affect the management of Stage II CRC patients and should be therefore included in reporting guidelines and staging systems in CRC.