The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis

Abstract Background: Upper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Urine cytology is a common clinical method for the early diagnosis of urologic neoplasms. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in Northeast China are rare. Methods: In this retrospective case-control study, we first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 142 patients with UUT-UC after radical nephroureterectomy (RNU). A nomogram model was established and we evaluated its effectiveness. Subsequently, after searching several databases, including PubMed, Embase, and Ovid, we quantitatively combined our results with the published data in a meta-analysis. Results: Our case-control study demonstrated that patients with muscle-invasive tumors (T2-T4) were more prone to preoperative positive urine cytology than those with non-muscle-invasive tumors (Tis-T1), suggesting that preoperative positive urine cytology may be associated with the aggressive form of UUT-UC. Kaplan-Meier curves demonstrated that the patients with positive urine cytology had significantly poorer intravesical recurrence-free survival (IV-RFS). Additionally, preoperative urine cytology (hazard ratio, HR=3.24) and lymph node status (HR=2.67) were validated as significant independent predictors of intravesical recurrence by multivariate analysis. Nomogram, calibration plots, AUC values and the C-index demonstrated that the predictive accuracy was significantly improved when preoperative urine cytology was combined. Subsequently, adding to our study, 11 eligible articles from 2010 to 2016 containing 2942 patients were sifted out for our meta-analysis. Overall analysis showed that preoperative positive urine cytology was associated with a 56% increased risk of intravesical recurrence (HR=1.56). In the subgroup analysis by region, study type, and sample size, the pooled HR was statistically significant for the Japan subgroup (HR=1.45), China subgroup (HR=1.66), cohort study subgroup (HR=1.44), and case-control study subgroup (HR=1.77), the subgroup with sample size greater than or equal to 100 (HR=1.42), and the subgroup with sample size less than 100 (HR=2.95). Conclusions: Preoperative urine cytology significantly correlated with intravesical recurrence in patients with UUT-UC after RNU, although these results need to be interpreted with caution. Large, prospective trials are required to further confirm its prognostic significance.