The impact of variant histological differentiation on extranodal extension and survival in node positive bladder cancer treated with radical cystectomy

Abstract

Objective: To investigate the impact of variant urothelial carcinoma of the bladder (UCB) histologies on extra nodal extension (ENE) and survival in lymph node (LN) positive bladder cancer patients undergoing radical cystectomy (RC).

Material and methods: We meticulously reviewed all bladder specimens for presence of variant UCB histologies and LN specimen for presence and extent of ENE in 517 UCB patients treated with RC. Descriptive statistics, the Kaplan Meier method and multivariable Cox regression models evaluated the association between variant UCB histology, ENE and survival metrics including disease recurrence-free, cancer-specific, and overall survival, respectively.

Results: Overall, 138 patients had LN metastasis (27%), with a median number of 15 (IQR 9; 18) LNs removed. Among LN positive patients, 43 (31%) had ENE with a median length of 10 mm. Variant histology was present in 96 patients (18.6%) with squamous cell (12.0%) and sarcomatoid (2.5%) differentiation being the most common. In all patients, the presence of variant histology was neither associated with presence of LN metastasis nor ENE (all p-values = n.s.). In Kaplan-Meier analyses the presence of LN metastases and ENE in LN positive patients was significantly associated with disease recurrence and cancer-specific mortality, respectively (all p < 0.001). The presence of variant histology did not influence these outcomes (p = n.s.). In multivariable analyses, adjusted for standard UCB prognosticators, ENE, but not variant histology, independently predicted disease recurrence-free (hazard ratio (HR) 3.88, 95% confidence intervall (CI) 2.24-6.71, p < 0.001), cancer-specific (HR 4.60; 95% CI, 2.57-8.23, p < 0.001), and overall survival (HR 3.51; 95% CI, 2.10-5.86, p < 0.001).

Conclusion: Variant UCB histologies do not seem to increase the incidence of LN metastasis or ENE. This study confirms ENE being a powerful predictor for outcomes in node positive UCB patients - regardless of variant histological differentiation. Our findings warrant validation in larger cohort setting.

Keywords: Extra nodal extension; Histology; Lymph node metastasis; Radical cystectomy; Urinary bladder cancer; Urothelial carcinoma.