Tumor budding, a novel prognostic indicator for predicting stage progression in T1 bladder cancers

Abstract

Tumor budding has been defined as an isolated single cancer cell or a cluster composed of fewer than five cancer cells scattered in the stroma. It is a strong predictor for lymph node metastasis in T1 colorectal cancer. We introduced this concept to T1 non‐muscle invasive bladder cancer and evaluated whether tumor budding could have a prognostic impact on the clinical outcome. We identified 121 consecutive patients with newly diagnosed T1 bladder cancer between 1994 and 2014 at Keio University Hospital. All slides were re‐reviewed by a dedicated uropathologist. Budding foci were counted under ×200 magnification. When the number of budding foci was 10 or more, tumor budding was defined as positive. The relationship between tumor budding and clinical outcomes was assessed using a multivariate analysis. The median follow‐up was 52 months. Tumor budding was positive in 21 patients (17.4%). Tumor budding was significantly associated with T1 substaging, tumor architecture and lymphovascular invasion. The 5‐year progression‐free survival rate in T1 bladder cancer patients with tumor budding was 53.8%, which was significantly lower than that in patients without tumor budding (88.4%, P = 0.001). A multivariate Cox regression analysis revealed that tumor budding was independently associated with stage progression (P = 0.002, hazard ratio = 4.90). In a subgroup of patients treated with bacillus Calmette‐Guérin instillation (n = 88), tumor budding was also independently associated with stage progression (P = 0.003, hazard ratio = 5.65). Tumor budding may be a novel indicator for predicting stage progression in T1 bladder cancer, and would likely be easily introduced in clinical practice.

Does evaluation of tumour budding in diagnostic biopsies have a clinical relevance? A systematic review

“…The ability of tumour budding to prognosticate nodal metastasis has also been reported in other cancers . Moreover, the prognostic impact of tumour budding for nodal metastasis, patient survival or both was prominent in the early stages of other cancers . These findings indicate that tumour budding is an important step in the development of metastasis.…”

“…2,29 Moreover, the prognostic impact of tumour budding for nodal metastasis, patient survival or both was prominent in the early stages of other cancers. [30][31][32] These findings indicate that tumour budding is an important step in the development of metastasis.…”

Tumor Budding, Micropapillary Pattern, and Polyploidy Giant Cancer Cells in Colorectal Cancer: Current Status and Future Prospects

“…The number of tumor buddings has negative correlations with the degree of tumor differentiation. There are more tumor buddings in minimally differentiated CRCs than in the highly differentiated and moderately differentiated CRCs [57, 62–65]. In clinical practice, Dukes staging system has been widely used for CRC classification for many years because it can effectively predict the disease prognosis.…”

Infiltrative lamina propria invasion pattern as an independent predictor for cancer‐specific and overall survival of instillation treatment‐naïve stage T1 high‐grade urothelial bladder cancer

“…In the present study on 322 T1-HG BC patients who all had a re-TUR before conservative management, we identified lamina propria invasion pattern, WHO 1973 grade and metric stage pT1 substaging as significant variables to predict clinical outcome for T1-HG BC patients in Kaplan-Meier analysis. 13,14 Taken together, the prognostic value of invasion border configuration in NMIBC is probably derived from differential activation of the EMT program, and could represent a powerful histomorphological surrogate for the grade of EMT activation. Together with associated CIS and grade 3 (after WHO classification 1973), which were independent predictors of PFS, this feature should lead at least to instillation treatment with BCG.…”