The prognostic value of tumor budding in patients who had surgery for rectal cancer with and without neoadjuvant therapy.

Background: The aim of this study was to investigate the prognostic value of tumor budding (TB) in rectal cancer patients. TB in the specimens of patients who received neoadjuvant chemoradiotherapy was specifically analyzed.

Methods: This study was conducted on rectal cancer patients treated at Dokuz Eylul University Hospital, Turkey, between January 2000 and June 2010. Prospectively recorded clinicopathological data and the oncological outcomes of patients who received neoadjuvant chemoradiotherapy (CRT) (n = 117) and also patients who did not receive it (n = 113) were analyzed. TB was defined as an isolated single cancer cell or a cluster of cells composed of less than 5 cells of a "budding focus". Budding intensity was scored as follows: none (0), mild (1-5 buds), moderate (6-10 buds), and severe (> 10 buds). Two tumor budding intesity groups were created, TB-1 (none, few) and TB-2 (moderate, severe) for statistical analysis.

Results: The median follow-up time was 40.12 ± 27.5 months. The 5-year overall and disease-free survival (DFS) rates were 66% and 62%, respectively. Multivariate analysis of overall survival in all patients showed that TB intensity (HR 2.64; 95% CI 1.46-4.77) and radial margin status (HR 2.16; 95% CI 1.18-3.96) were independent predictors of decreased overall survival. In patients who received CRT, TB (HR 4.87; 95% CI 2.10-11.28) and distant metastasis (HR 4.31; 95% CI 1.81-10.22) were predictive of survival while in patients who did not receive CRT, TB (HR 4.28; 95% CI 1.60-11.49), distant metastasis (HR 2.33; 95% CI 1.19-4.60), radial margin status (HR 2.53; 95% CI 1.09-5.91), and venous invasion (HR 4.48; 95% CI 2.14-9.39) were significantly independent predictors of survival. In multivariate analysis of all patients decreased DFS was correlated with lymph node involvement (HR 2.78; 95% CI 1.60-4.87), venous invasion (HR 1.76; 95% CI 1.00-3.09), and with radial margin status (HR 2.31; 95% CI 1.27-4.22). In multivariate analysis in the CRT group, decreased DFS was significantly associated with lymph node involvement (HR 4.39; 95% CI 1.70-11.33) and radial margin status (HR 2.56; 95% CI 1.12-5.90) while only lymph node involvement (HR 2.33; 95% CI 1.16-4.66) was a significant predictor of decreased DFS in patients who did not receive CRT.

Conclusions: TB has prognostic value as important as lymph node involvement and radial margin status and it may be a helpful prognostic indicator even after CRT. TB should be included in the TNM classification and may be used in planning adjuvant therapy.