Prognostic Value of Concomitant Carcinoma In Situ in the Radical Cystectomy Specimen: A Systematic Review and Meta-Analysis

Purpose: We investigated the prognostic impact of concomitant carcinoma in situ in radical cystectomy specimens. Materials and Methods: We performed a systematic review and meta-analysis using MEDLINE (R), Scopus (R), Web of Science (TM) and The Cochrane Library to identify eligible studies published until October 2017. Studies were eligible for analysis if they compared patients with concomitant carcinoma in situ in radical cystectomy specimens for bladder cancer to patients without concomitant carcinoma in situ to determine its value to prognosticate overall mortality, recurrence-free survival, cancer specific mortality and ureteral involvement using multivariable analysis. The protocol for this systematic review was registered in PROSPERO (Prospective Register of Systematic Reviews, CRD42018086539) and is available in full on the University of York website. Results: Overall 23 studies published between 2006 and 2017 including a total of 20,647 patients were selected for the systematic review and meta-analysis. Concomitant carcinoma in situ was reported in 39.4% of radical cystectomy specimens. In studies analyzing all patients the presence of concomitant carcinoma in situ was not associated with overall mortality (pooled HR 0.92, 0.77-1.10), recurrence-free survival (pooled HR 1.06, 0.99-1.13) or cancer specific mortality (pooled HR 1.00, 0.93-1.07). It was associated with ureteral involvement (pooled OR 4.51, 2.59-7.84). On subanalysis of studies restricted to patients with organ confined bladder cancer at radical cystectomy concomitant carcinoma in situ was associated with worse recurrence-free survival (pooled HR 1.57, 1.12-2.21) and cancer specific mortality (pooled HR 1.51, 1.001-2.280). Conclusions: Concomitant carcinoma in situ is significantly associated with ureteral involvement in patients treated with radical cystectomy. In patients with organ confined disease concomitant carcinoma in situ in the radical cystectomy specimen is a prognosticator of recurrence-free survival and cancer specific mortality.