Abstract
BackgroundThe role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively. In case of negative cystoscopy the additional prognostic value of these markers has not been clearly defined yet. The present study is the first systematic approach to directly compare the ability of a urine marker panel to predict the risk of recurrence and progression in bladder cancer (BC) patients with no evidence of relapse during surveillance for NMIBC.MethodsOne hundred fourteen patients who underwent urine marker testing during surveillance for NMIBC and who had no evidence of BC recurrence were included. For all patients cytology, Fluorescence-in-situ-hybridization (FISH), immunocytology (uCyt+) and Nuclear matrix protein 22 enzyme-linked immunosorbent assay (NMP22) were performed. All patients completed at least 24 months of endoscopic and clinical follow-up of after inclusion.ResultsWithin 24 months of follow-up, 38 (33.0%) patients experienced disease recurrence and 11 (9.8%) progression. Recurrence rates in patients with positive vs. negative cytology, FISH, uCyt+ and NMP22 were 52.6% vs. 21.9% (HR = 3.9; 95% CI 1.75-9.2; p < 0.001), 47.6% vs. 25.0% (HR 2.7; 1.2-6.2; p = 0.01), 43.8% vs. 22.4% (HR 3.3; 1.5-7.6; p = 0.003) and 43.8% vs. 16.7% (HR 4.2; 1.7-10.8; p = 0.001). In patients with negative cytology, a positive NMP22 test was associated with a shorter time to recurrence (p = 0.01), whereas FISH or uCyt+ were not predictive of recurrence in these patients. In the group of patients with negative cytology and negative NMP22, only 13.5% and 5.4% developed recurrence and progression after 24 months.ConclusionsPatients with positive urine markers at time of negative cystoscopy are at increased risk of recurrence and progression. In patients with negative cytology, only NMP22 is predictive for recurrence. Patients with negative marker combinations including NMP22 harbour a low risk of recurrence. Therefore, the endoscopic follow-up regimen may be attenuated in this group of patients.
Highlights
The role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively
Correlation of single urine markers with recurrence and progression Rates of recurrence and progression and after 12 and 24 months in patients with negative and positive cytology, fluorescence-in-situ hybridization (FISH), uCyt+ and Nuclear matrix protein 22 (NMP22) are summarized in Tables 2 and 3
Anticipatory positive urine marker combinations As cytology is the test most commonly used for surveillance of BC patients, we evaluated whether in patients with negative cytology, the results of other markers influence the risk of recurrence
Summary
The role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively. The present study is the first systematic approach to directly compare the ability of a urine marker panel to predict the risk of recurrence and progression in bladder cancer (BC) patients with no evidence of relapse during surveillance for NMIBC. Patients with non-muscle invasive bladder cancer (NMIBC) harbour a significant risk of tumor recurrence and progression [1]. Urine cytology is recommended as standard in the follow-up of patients with NMIBC, as it is a non-invasive procedure with the potential to detect flat lesions not visible in cystoscopy [5]. Its sensitivity is satisfactory only for high grade tumors or carcinoma in situ Newer markers such as fluorescence-in-situ hybridization (FISH), immunocytology (uCyt+) or Nuclear matrix protein 22 (NMP22) have shown increased sensitivitity compared to cytology [6,7]. The clinical implications and the optimal management of these patients with negative cystoscopy or biopsy and concomitantly positive markers remain to be defined
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