Significance of Positive Urine Cytology on Progression and Cancer-Specific Mortality of Non-Muscle-Invasive Bladder Cancer

This prospective study, consisting of 326 patients with non-muscle-invasive bladder cancer (NMIBC) who underwent 597 tumor resections, demonstrated that a voided urine cytology result that is positive for atypical cells is a predictor of disease progression, independent of histological grade. Time-dependent covariate Cox models appear more sensitive in detecting risk factors for NMIBC progression than conventional time-fixed models. Voided urine cytology may be useful for NMIBC risk stratification. Background: Positive results from voided urine cytology (VUC) indicate the fragility of the intercellular adhesion of bladder cancer cells, a critical biological process for invasion and metastasis, along with the presence of atypical cells. Few studies have focused on the prognostic role of VUC in non-muscle-invasive bladder cancer (NMIBC). Methods: Between 2000 and 2010, 326 patients diagnosed pathologically with Ta or T1 bladder urothelial carcinoma underwent 597 transurethral resections of bladder tumor (TURBTs). Clinicopathological data were prospectively collected at each TURBT. Reports of cells of class IIIb or greater were considered positive VUC results. Muscle-invasive or metastatic recurrences were considered progression. Risk factors for progression and cancer-specific mortality (CSM) were determined using time-fixed and time-dependent Cox models. Variables at the study entry and at each TURBT were used for time-fixed and time-dependent models, respectively. Results: The 5-year cumulative progression and CSM rates were, respectively, 7% and 5% (median follow-up, 46 months). The 5-year cumulative progression and CSM rates for patients with positive VUC were 20% and 15%, respectively, compared with 2% (P < .0001) and 2% (P = .0002), respectively, for patients with negative VUC results. A positive VUC result was a significant and independent risk factor for progression and CSM in the time-fixed and time-dependent models. In time-dependent models, 7 predictors for progression or CSM were identified (positive VUC results, T1 disease, lack of intravesical instillation, higher prior recurrence rate, higher histological grade, male gender, and advanced age), whereas 3 predictors were identified in time-fixed models (positive VUC, T1 disease, and higher prior recurrence rate). VUC results consistently outperformed histological grade as a prognostic predictor. Conclusion: Positive VUC results predict the progression and CSM of NMIBC, independent of and outperforming histological grade.