Variant histology in urothelial carcinoma: associated factors and survival impact after radical cystectomy.

Abstract

Purpose: To investigate the factors associated with variant histology (VH) and prognostic significance of VH in urothelial carcinoma (UC) among patients undergoing radical cystectomy (RC) with ileal conduit urinary diversion.

Methods: A retrospective analysis was conducted on 317 patients who underwent RC with ileal conduit diversion between 2019 and 2025. Patients were categorized based on the presence of VH in the final pathology. Demographic, clinical, perioperative, and pathological data were compared. Logistic regression was performed to identify factors associated with VH, while Kaplan-Meier and uni-multivariable Cox regression analyses evaluated overall survival (OS) and cancer-specific survival (CSS).

Results: VH was detected in 139 patients (43.8%), with squamous differentiation being the most prevalent variant, observed in 80 patients of the 317 patients who underwent RC with ileal conduit urinary diversion. Presence of hydronephrosis, clinical lymph node positivity and WBC > 7695 g/dl were defined as factors associated with VH in multivariate logistic regression analysis. Kaplan-Meier survival analysis illustrated a statistically significant reduction in OS and CSS among patients harboring VH compared to those with pure UC following RC and ileal conduit urinary diversion (53.8 vs. 36.8 months for OS and 68 vs. 53 months for CSS, log-rank test, p < 0.001). Multivariable Cox regression analysis revealed that presence of variant histology was associated with reduced OS (HR = 1.624; 95% CI = 1.094-2.411; p = 0.016) and CSS (HR = 1.945; 95% CI = 1.043-3.626; p = 0.036).

Conclusion: VH in UC is associated with advanced disease and poorer survival outcomes following RC. Certain preoperative factors-hydronephrosis, clinical lymphadenopathy, and elevated WBC-may be associated with the presence of VH. Early recognition of these features could guide individualized treatment strategies and improve prognostic assessment. However, the retrospective and single-center nature of this study may introduce selection and information bias, and the findings should be interpreted with caution until validated by prospective multicenter trials.