Systematic Review on the Fate of the Remnant Urothelium after Radical Cystectomy

Abstract

Context: Urothelial carcinoma is considered a pan-urothelial disease. As such, the remnant urothelium in the upper urinary tract and urethra following radical cystectomy (RC) remains at risk for secondary urothelial tumors (SUTs).

Objective: To describe the incidence, diagnosis, treatment, and outcomes of patients with SUTs after RC.

Evidence acquisition: A systematic search was conducted using PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2016 reporting on malignant diseases of the urothelium after RC for bladder cancer. The search strategy separated between upper and lower tract urothelial tumors.

Evidence synthesis: Of a total of 1069 studies, 57 were considered for evidence synthesis. SUTs occured in approximately 4-10% of patients after RC. Carcinoma in situ of the bladder, a history of nonmuscle invasive bladder cancer, and tumor involvement of the distal ureter are the strongest risk factors for secondary upper tract tumors. Risk factors for secondary urethral tumors represent urothelial malignancy in the prostatic urethra/prostate and bladder neck (in women), nonorthotopic diversions, and positive findings on permanent sections. The majority of patients (84%) with SUTs, presented with urothelial recurrence without evidence of metastasis. Of those, 84.0% were treated with surgery, 10.5% with systemic chemotherapy and/or radiotherapy, and 5.6% with topical chemotherapy and/or immunotherapy. After a median follow-up of 91 mo (range: 26-155), 65.9% of patients died of disease and 21.5% died of other causes. Detection and treatment of SUTs at an asymptomatic stage can reduce the risks of cancer-specfific and overall mortality by 30%. A limitation of the study is that the available data were retrospective.

Conclusions: SUTs are rare oncological events and most patients have an adverse prognosis despite absence of distant disease at diagnosis. Therefore, surveillance of the remnant urothelium should be implemented for patients with histological features of panurothelial disease as it may improve timely detection and treatment.

Patient summary: Secondary tumors of the renal pelvis, ureters, and urethra occur in approximately 4-10% of patients after radical removal of the bladder for bladder cancer. These patients' prognoses are reduced, likely due to delayed diagnosis. Therefore, routine surveillance might be important to detect tumors at an early stage.

Keywords: Bladder cancer; Radical cystectomy; Recurrence; Remnant; Upper urinary tract; Urethra; Urothelium.