Replacing cystoscopy by urine markers in the follow-up of patients with low-risk non–muscle-invasive bladder cancer?—An International Bladder Cancer Network project

• The aim of this study was to investigate if the use of a molecular urine marker (immunocytology) might replace cystoscopy in the follow-up of patients with pTa G1-2 bladder cancer.
• uCyt+had a high specificity of 82.8%. Sensitivity was higher in primary (92.3%) as compared with recurrent (65%) disease.
• In a longitudinal approach 232 patient visits of 36 patients including cytology, immunocytology, and cystoscopy were analyzed.
• Restricting cystoscopy to marker-positive patients would have resulted in 35% of recurrent tumors being overlooked or diagnosed later.
• In contrast 74% of cystoscopies and 5 negative TURBs would have been saved.

RationaleNumerous molecular urine markers for the diagnosis of bladder cancer have been developed and evaluated mostly in case-control settings through the past decades. However, despite all efforts none of them has been included into clinical decision-making and guideline recommendations until today. The aim of this retrospective longitudinal analysis was to investigate if a molecular marker might be able to replace cystoscopy as a primary examination in diagnosis and follow-up of patients with pTa grade 1-2 bladder cancer.Materials and methodsTotally 36 patients (32 men) with pTa grade 1-2 bladder cancer underwent 232 follow-up examinations including urine analysis, cytology, immunocytology (uCyt+), and urethrocystoscopy (UC). Mean age at study entry was 63 years. Patients were observed through a median follow-up interval of 3.8 years.ResultsIn summary, 47 Transurethral Resection of Bladder Tumors (TURB) procedures were indicated based upon a positive UC (44) or as re-TURB (3) and 33 tumors (plus 1 case of pTa G0) were histopathologically confirmed. Although uCyt+was positive in 12/13 primary tumors (92.3%), sensitivity dropped to 13/20 (65%) in tumor recurrence presumably because of their smaller size. Urine cytology had a sensitivity and a specificity of 30.3% and 94.9%, respectively, but did not improve the sensitivity of uCyt+alone. If UC was based upon a positive uCyt+test, 8/33 tumors (24.2%) would have been overlooked or diagnosed late. In contrast, 173 UCs (74%) would have been saved and 5 presumably unnecessary TURB procedures would not have been indicated.ConclusionsThis longitudinal study suggests a potential of molecular urine tests in replacing cystoscopy in the follow-up of patients with pTa G1-2 bladder cancer. The use of additional markers might further improve sensitivity of urine testing. A prospective randomized study has been initiated to prospectively investigate the performance of a marker panel against UC.