Oncological outcomes of concomitant carcinoma in situ at radical cystectomy in pure urothelial bladder cancer and in histological variants.

Introduction: The presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants.

Methods: We evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage.

Results: Median age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease). Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomy Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants.

Conclusion: Concomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.