Tumor budding in upper urinary tract urothelial carcinoma: a putative prognostic factor for extraurothelial recurrence and overall survival.

Tumor budding, defined as a single cancer cell or clusters of fewer than five cancer cells observed at the tumor invasion front, has been reported to be associated with poor prognosis in various types of cancers. However, limited information regarding the pathological and prognostic significance of tumor budding in upper urinary tract urothelial carcinoma (UUTUC) is available. We investigated 135 consecutive patients with newly diagnosed invasive UUTUCs (73 with renal pelvic cancers and 62 with ureteral cancers) treated with nephroureterectomy or partial ureterectomy between 1999 and 2018 in our hospital. Under a × 200 magnification, tumors with 10 or more budding foci were defined as "high tumor budding". The median follow-up period was 53.6 months. Among the 135 patients, 41 (30%; 16 with renal pelvic cancers and 25 with ureteral cancers) showed high tumor budding. High tumor budding was related to adjuvant chemotherapy status, higher pathological T stage, lymphovascular invasion, lymph node metastasis, tumor location, concomitant variant histology, and non-papillary gross finding. The multivariate Cox analysis revealed that LVI and high tumor budding were independent predictors for extraurothelial recurrence (P = 0.039 and 0.014, hazard ratio = 2.50 and 2.88, respectively), and high tumor budding was an independent predictor for overall survival (P = 0.024, hazard ratio = 2.33). Tumor budding can be easily introduced in clinical practice with no need for immunohistochemical analysis, may be an important clinicopathological factor of UUTUC, and is suggested to be useful as a novel predictive prognostic factor of patients with invasive UUTUC.