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 ther 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.

Response to Re: Role of routine computed tomography scan in the oncological follow up of patients treated by radical cystectomy for bladder cancer

“…In our cohort, likely due to a statistically underpowered analysis inherent to the limited number of recurrences in the remnant urothelium ( n = 15), we found no predictive factors of urethral or ureteral recurrence despite assessing the predictors usually reported in previous series (including carcinoma in situ , tumor multifocality, positive ureteral or urethral margin, prostatic stromal involvement etc.) . In the same way, we did not find any statistically significant differences between patients with ileal conduit versus orthotopic neobladder in terms of urethral recurrence rates (5.5% vs 4.3%; P = 0.78).…”

“…The main concerns the author raises deal with recurrences in the remnant urothelium. As he emphasizes, several risk factors of urethral and ureteral recurrence after radical cystectomy have been suggested in the past few years . In our cohort, likely due to a statistically underpowered analysis inherent to the limited number of recurrences in the remnant urothelium ( n = 15), we found no predictive factors of urethral or ureteral recurrence despite assessing the predictors usually reported in previous series (including carcinoma in situ , tumor multifocality, positive ureteral or urethral margin, prostatic stromal involvement etc.)…”

“…However, as secondary urothelial tumors are one of the rarest “recurrences” after radical cystectomy, for which diagnosis in the non‐invasive or early invasive stages might be associated with beneficial long‐term prognosis, we concur with Besiroglu that the early detection of these recurrences should be prioritized . In that regard, and despite doubt regarding the role of risk‐stratified oncological follow‐up protocols, as they might be associated with poor compliance from the medical community, the use of dedicated follow‐up protocols in patients with risk factors of recurrence in the remnant urothelium could be an interesting option.…”

Risk factors, follow-up, and treatment of urethral recurrence following radical cystectomy and urinary diversion for bladder cancer: a meta-analysis of 9498 patients

“…Radical cystectomy (RC) with urinary diversion is a crucial urological procedure for the treatment of muscle-invasive bladder cancer (BCa) [ 1 – 3 ]. Furthermore, RC is an important therapeutic option for patients diagnosed with high-risk non–muscle-invasive BCa, recurrent non–muscle-invasive BCa, recurrent carcinoma in situ (CIS) following intravesical perfusion with bacillus Calmette-Guerin (BCG), or superficial carcinomas refractory to transurethral resection (TUR) and intravesical therapy [ 4 ].…”

Prognostic factors and outcomes of primary transitional cell carcinoma of the ureter: a population-based study

“…More men (2.7/100,000) than women (1.1/100.000) are likely to be affected. Primary transitional cell carcinoma of the ureter is an aggressive disease with a high progression rate, as over half of cases are invasive and approximately one-quarter of them have a regional metastasis at diagnosis compared to 15% and 20% for all bladder tumors [ 3 – 5 ]. Most patients with this disease have a single ureter affected, and the disease affects both ureters in only 2–4% of patients.…”