Background: Microsatellite analysis (MA) of voided-urine samples has been promoted as an alternative for cystoscopy surveillance (UCS) of patients with low-grade non-muscle-invasive papillary urothelial carcinoma (UC). Objective: To assess the feasibility and clinical utility of MA on voided-urine samples in a routine setting to detect or predict bladder cancer recurrences. Design, setting, and participants: We evaluated 228 patients monitored by MA of voided-urine samples and synchronous UCS who participated in a longitudinal prospective study in 10 hospitals. Follow-up started after diagnosis of a primary or recurrent pTa, pT1, grade 1 or grade 2 papillary UC. Measurements: Clinico-pathological parameters and fibroblast growth factor receptor 3 (FGFR3) gene mutation status of the inclusion tumour were determined. MA outcome was analysed in 1012 urine samples during a mean follow-up of 41 mo. Poor DNA quality prevented MA in 19% (197/1012) of the samples, leaving 815 visits for a cross-sectional analysis of sensitivity and specificity. We determined the predictive value (PPV) in a longitudinal analysis for 458 series with persistent MA results. Factors influencing diagnostic quality of MA were investigated. Kaplan-Meier analysis was performed to relate MA results to recurrence. Results and limitations: Cross-sectional sensitivity and specificity of MA for detection of a recurrence were 58% (49/84) and 73% (531/731), respectively. One pT1 grade 3 UC was missed. In a longitudinal analysis, the 2-yr risk to develop a recurrence reached 83% if MA outcome was persistently positive and 22% when MA was persistently negative. PPV of MA was higher with wild-type FGFR3 gene status and smoking habits. All four upper urinary tract tumours detected were preceded by a positive MA test. Conclusions: Consecutive positive MA results are a strong predictor for future recurrences, but sensitivity needs to be improved, for example, by patient selection and testing of additional genetic markers in urine samples.

Additional Metadata
Keywords Bladder cancer, Follow-up, Microsatellite analysis, Non-muscle-invasive UC, Trial, Urine test
Persistent URL dx.doi.org/10.1016/j.eururo.2008.05.001, hdl.handle.net/1765/24363
Citation
van der Aa, M.N.M., Zwarthoff, E.C., Steyerberg, E.W., Boogaard, M.W., Nijsen, Y., van der Keur, K.A., … van der Kwast, Th.H.. (2009). Microsatellite Analysis of Voided-Urine Samples for Surveillance of Low-Grade Non-Muscle-Invasive Urothelial Carcinoma: Feasibility and Clinical Utility in a Prospective Multicenter Study (Cost-Effectiveness of Follow-Up of Urinary Bladder Cancer Trial [CEFUB]). European Urology, 55(3), 659–668. doi:10.1016/j.eururo.2008.05.001