Prognostic and Predictive Value of Tumor Budding in Colorectal Cancer

ABSTRACT Background: Tumor budding (TB) is an adverse prognostic factor in colorectal cancer (CRC). International consensus on a standardized assessment method has led to its wider reporting. However, uncertainty regarding its clinical value persists. This study aimed to (1) confirm the prognostic significance of TB, particularly in stage II CRC; (2) determine optimum thresholds for TB risk grouping; and (3) determine whether TB influences responsiveness to chemotherapy. Methods: TB was assessed in CRC sections from 1575 QUASAR trial patients randomized between adjuvant chemotherapy and observation. Optimal risk group cutoffs were determined by maximum likelihood methods, with their influence on recurrence and mortality investigated in stratified logrank analyses on ‘exploratory’ (n=504), ‘hypothesis testing’ (n=478) and ‘final’ (n=593) datasets. Results: The optimal threshold for high grade TB (HGTB) was 10+ buds/1.23 mm2. HGTB tumors had significantly worse outcome than those with lower TB: 10-year recurrence 36% vs 22% (risk ratio [RR]=2.00 [95%CI 1.62–2.45], 2p Conclusions: TB is a strong independent predictor of recurrence. Chemotherapy efficacy is comparable in patients with higher and lower TB, hence absolute reductions in recurrence and death with chemotherapy should be about twice as large in patients with 10+ than