CONTEXT: Surveillance of the urethra and management of urethral recurrence (UR) after radical cystectomy (RC) is an area with poor evidence. OBJECTIVE: We aimed to summarize the available evidence and provide clinicians with practical recommendations on how to prevent and manage UR after RC for bladder cancer. EVIDENCE ACQUISITION: The MEDLINE and EMBASE databases were searched during September 2021 for studies evaluating UR after RC. The primary endpoint was oncologic outcomes for patients who experienced UR depending on different surveillance and management approaches. EVIDENCE SYNTHESIS: Forty-three studies were included in the quantitative synthesis. According to the currently available literature, a tight-knitted surveillance protocol should be implemented for males treated with RC and nonorthotopic neobladder diversion as well as patients with prostatic involvement, tumor multifocality, bladder neck involvement, and concomitant carcinoma in situ. A survival benefit of a prophylactic urethrectomy has been reported only in patients at very high risk for UR based on clinical factors. Surveillance protocols were highly heterogeneous and poorly documented among included studies. Patients whose UR was diagnosed based on clinical symptoms had a poor prognosis. Only limited data were available on the comparative effectiveness of watchful waiting after RC versus clinical symptom screening as part of a follow-up strategy. However, the use of regular cytology and/or urethroscopy seems useful in select patients at high risk for UR. Despite limited data on the optimal management of UR, urethra-sparing approaches (transurethral resection of UR) seem to be an option for Ta (only) recurrences; a salvage urethrectomy with or without chemotherapy should be the standard for all others. CONCLUSIONS: Based on the currently available literature, we have proposed an algorithm to guide the decision-making process to help identify and treat UR after RC. Given the lack of evidence on how to deal with UR and surveil patients at risk for UR, this study may invigorate research in this area of unmet need. PATIENT SUMMARY: Early diagnosis and tailored management of urethral recurrence could help improve oncologic outcomes in these patients.
CONTEXT: During the past decade, several urinary biomarker tests (UBTs) for bladder cancer have been developed and made commercially available. However, none of these is recommended by international guidelines so far. OBJECTIVE: To assess the diagnostic estimates of novel commercially available UBTs for diagnosis and surveillance of non-muscle-invasive bladder cancer (NMIBC) using diagnostic test accuracy (DTA) and network meta-analysis (NMA). EVIDENCE ACQUISITION: PubMed, Web of Science, and Scopus were searched up to April 2021 to identify studies addressing the diagnostic values of UBTs: Xpert bladder cancer, Adxbladder, Bladder EpiCheck, Uromonitor and Cxbladder Monitor, and Triage and Detect. The primary endpoint was to assess the pooled diagnostic values for disease recurrence in NMIBC patients using a DTA meta-analysis and to compare them with cytology using an NMA. The secondary endpoints were the diagnostic values for high-grade (HG) recurrence as well as for the initial detection of bladder cancer. EVIDENCE SYNTHESIS: Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. In most of the studies, there was an unclear risk of bias. For NMIBC surveillance, novel UBTs demonstrated promising pooled diagnostic values with sensitivities up to 93%, specificities up to 84%, positive predictive values up to 67%, and negative predictive value up to 99%. Pooled estimates for the diagnosis of HG recurrence were similar to those for the diagnosis of any-grade recurrence. The analysis of the number of cystoscopies potentially avoided during the follow-up of 1000 patients showed that UBTs might be efficient in reducing the number of avoidable interventions with up to 740 cystoscopies. The NMA revealed that diagnostic values (except specificity) of the novel UBTs were significantly higher than those of cytology for the detection of NMIBC recurrence. There were too little data on UBTs in the primary diagnosis setting to allow a statistical analysis. CONCLUSIONS: Our analyses support high diagnostic accuracy of the studied novel UBTs, supporting their utility in the NMIBC surveillance setting. All of these might potentially help prevent unnecessary cystoscopies safely. There are not enough data to reliably assess their use in the primary diagnostic setting. These results have to be confirmed in a larger cohort as well as in head-to-head comparative studies. Nevertheless, our study might help policymakers and stakeholders evaluate the clinical and social impact of the implementation of these tests into daily practice. PATIENT SUMMARY: Novel urinary biomarker tests outperform cytology with the potential of improving routine clinical practice by preventing unnecessary cystoscopic examinations during the surveillance of non-muscle-invasive bladder cancer.
