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

Abstract

Objectives To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). Patients and Methods The study comprised 758 urine samples either collected from the bladder (n = 373) or UUT (n = 385). All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed. Results UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.

High performance of 5‐aminolevulinic acid‐induced fluorescent selective upper tract urinary cytology

“…However, due to potential cell damage, which is unavoidable when collecting upper urinary tract urine with a ureteral catheter, selective upper tract urinary cytology can occasionally show false positives. 11,17 Although we predicted an increase in the false positive rate due to catheter manipulation, as previously reported in NMP22, 18 the present study showed a false positive rate of 0%. This result indicated that 5-ALA-induced fluorescent selective upper tract urinary cytology was unaffected by catheterization.…”

“…Selective upper tract urinary cytology obtained by washing is the gold standard tool for detecting UTUC. However, due to potential cell damage, which is unavoidable when collecting upper urinary tract urine with a ureteral catheter, selective upper tract urinary cytology can occasionally show false positives . Although we predicted an increase in the false positive rate due to catheter manipulation, as previously reported in NMP22, the present study showed a false positive rate of 0%.…”

“…In recent years, various kinds of selective upper urinary tract urine biomarkers have been reported. We summarized the past reports on selective upper tract urine biomarkers in Table . The NMP22 test can easily be false positive as a result of catheter manipulation, so while its sensitivity is high (100%), its specificity is very low (5%).…”

“…For example, NMP22 showed high sensitivity for BT detection in voided urine samples, but in upper tract urinary samples, NMP22 had a high false positive rate, because an artificial catheter procedure is essential when collecting a selective upper urinary tract urine sample. 11 We previously reported that 5-ALA-induced fluorescent urine cytology using voided urine samples was more effective than conventional cytology for detecting UC. 12 By applying this method to upper tract urinary samples, we examined the utility of 5-ALA-induced fluorescent urine cytology for UTUC diagnosis.…”

“…Recently, the utility of various urinary biomarkers was reported to replace conventional urine cytology to improve the diagnostic accuracy of UTUC. For example, NMP22 showed high sensitivity for BT detection in voided urine samples, but in upper tract urinary samples, NMP22 had a high false positive rate, because an artificial catheter procedure is essential when collecting a selective upper urinary tract urine sample . We previously reported that 5‐ALA‐induced fluorescent urine cytology using voided urine samples was more effective than conventional cytology for detecting UC .…”