The impact of carcinoma in situ in ureteral margins during radical cystectomy: A case-controlled study

Background and objective: The presence of carcinoma in situ (Cis) in association with bladder cancer is associated with a poor prognosis. However, the prognosis associated with the presence of Cis in ureteral margins (CUM) during radical cystectomy has been poorly defined. To assess the prognosis associated with the presence of Cis in ureteral margins in patients with pM0 bladder cancer who have not undergone neoadjuvant chemotherapy.

Materials and methods: A retrospective case-control study was conducted between 2001 and 2016 using data from one academic center in France. From 1,450 radical cystectomies, 122 patients (case) who had CUM were matched according to age, sex, pTNM stage and urinary diversion method with a population sample of 122 patients (controls) who did not have Cis in ureteral margins during radical cystectomy. The survival analysis was performed by Kaplan-Meier using a (95%) CI. Multivariate Cox regression analysis was used to test the effect of CUM on cancer-specific survival. Recurrence-free survival was defined as a recurrence of urothelial carcinoma in the upper urinary tract.

Results and limitations: The mean follow-up period was 55.43 ± 39.6 months. The rate of Cis in the bladder in the CUM cases group was evaluated at 11.47%. The median overall and specific survival was inferior in the CUM cases group estimated at 43.3 [35.33-56.93] months, 52.43 [42.16-68.93] months respectively compared to the control group with a significant difference (P= 0.001, P= 0.0039). The cumulative probability of urothelial recurrence-free survival was decreased in the case group compared with the control group (63.9% vs. 92.6%, P = 0.0001). Multivariate analysis shown that urothelial recurrence was associated with CUM [(P <0.001), (HR adjusted =11.31), (95% CI): (3.38-37.77)] and the macroscopic appearance of the ureter (thickened, dilated) [(P= 0.003), (HR adjusted =4.62), (95% CI): (3.31-8.84)].

Conclusion: CUM is a poor prognostic factor that impacts cancer-specific survival and Recurrence-free survival. The presence of CUM has been independently associated with a significant increase in the risk of urothelial recurrence, and a decrease in both overall and specific survival. This supports the use of frozen section analysis to complete radical cystectomy without CUM.