Stepwise Application of Urine Markers to Detect Tumor Recurrence in Patients Undergoing Surveillance for Non-Muscle-Invasive Bladder Cancer

Abstract

Background. The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods. 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results. 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. Conclusions. Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.

Comparison of the diagnostic performance of fluorescence in situ hybridization (FISH), nuclear matrix protein 22 (NMP22), and their combination model in bladder carcinoma detection: a systematic review and meta-analysis

“…Consequently, there were 21 studies left for full-text reading. After scrutinizing the full-text of the 21 studies, 14 studies were discarded: two did not evaluate diagnostic values of FISH or NMP22,26 one with number of controls <20,10 three were prognostic analyses,11,27,28 and eight studies did not report diagnostic performance of the combination of FISH and NMP22 12–14,29–33. Finally, seven studies were suitable for our meta-analysis 16–22…”

Selected protein expression in a new prognostic model for patients with non-muscle-invasive bladder cancer

“…Attempts have been made by many researchers to improve the algorithms developed by the EORTC. Some authors have focused on the preparation of prognostic models for specific groups of patients, while others have attempted to determine the probability of tumor recurrence by evaluating gene polymorphisms, inflammation, or the presence of tumor markers in urine (Ieda et al 2016;Kim et al 2016;Maturana et al 2016;Chen et al 2012;Cui et al 2017;Todenhöfer et al 2014;Lammers et al 2016). The possibility of improving the accuracy of these algorithms by means of immunohistochemistry was also analyzed (Ding et al 2014;Passoni et al 2016).…”

Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?

“…Several studies have discussed the relevance of urine markers to detect UUT UC [ 3 , 5 , 6 ]. Still, urine cytology is the only marker, which is recommended by current guidelines, even if it is known to be less sensitive for the detection of UUT UC compared to UC of the bladder [ 2 ].…”