Tumor Budding: Prognostic Value in Muscle-invasive Bladder Cancer

Abstract

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. 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. 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." According to our results, TB becomes an independent predictor factor for cancer-specific mortality in MIBC, with a cut-off point of 14 "buds."