Prognostic risk stratification of pathological stage T3N0 bladder cancer after radical cystectomy

Purpose: Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk. Materials and Methods: The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised. Results: Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively. Conclusions: We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.