Tumor Budding: Prognostic Value in Muscle-invasive Bladder Cancer

OBJETIVES To assess if tumor budding (TB) behaves as a poor prognostic factor in muscle-invasive bladder carcinoma (MIBC). TB is the presence of tumor cells isolated or in small groups of fewer than 5 cells located at the tumor invasion front. MATERIAL AND METHODS Retrospective study of 106 patients with MIBC who underwent radical cystectomy. A cytokeratin AE1/AE3 immunostaining was applied to identify and quantify TB by the hot-spot method. The variables evaluated were: age, gender, Tumour, Node, Metastasis Classification (TNM) stage, associated Carcinoma in situ, differentiation degree, tumor size, tumor location, lymphatic, venous or perineural invasion, p53, Ki67, molecular subtype (basal/luminal) and chemotherapy. Main variables were overall and cancer-specific survival. RESULTS The mean follow-up time was 47 +/- 46.45 months. The mean TB count was 32.3 +/- 25.9 buds. The ROC curve established 14 buds as the cut-off point: the median survival rate for the low-grade TB group (<= 14 buds) was 69.5 months, and for the high-grade TB group (>14 buds) was 18.5 months (P= .003). In the multivariate analysis, independent predictive variables regarding mortality were: age, TB, and TNM stage. Patients with more than 14 buds had 2.27 times more risk of mortality, 95%CI:1.19-4.34, P = .013. In addition, the risk of mortality rises progressively as the number of buds increases, at a rate of 2% per bud. CONCLUSION According to our results, TB becomes an independent predictor factor for cancer-specific mortality in MIBC, with a cut-off point of 14 buds. (C) 2019 Elsevier Inc.