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Abstract

We totally agree with the author of the Editorial Comment that patients with suspect of urothelial cell carcinoma due to symptoms such as painless gross hematuria should undergo a complete workup including cystoscopy, upper urinary tract (UUT) imaging, and urine markers. In these cases, urine markers cannot replace invasive diagnostic measures. But how do we proceed in patients with negative cystoscopy results, normal imaging findings, and a positive urine marker? Current guidelines provide no clear recommendations for these patients. Because of the risk of missing a non-papillary bladder tumor (eg, CIS) by cystoscopy and the high specificity of cytology, the presence of positive cytology results should alert urologists. One option for further diagnosis would be to re-perform 5-aminolaevulinic acid (ALA)–guided cystoscopy, which has been shown to be more sensitive than white-light cystoscopy, particularly for the detection of CIS. 1 Stenzl A. Penkoff H. Dajc-Sommerer E. et al. Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy: a multicenter randomized, double-blind, placebo-controlled trial. Cancer. 2001; 117: 938-947 Crossref Scopus (92) Google Scholar , 2 Hungerhuber E. Stepp H. Kriegmair M. et al. Seven years' experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology. 2007; 69: 260-264 Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar In case of a negative finding, the performance of UUT urine sampling may help to identify the source of positive cytology. Given our findings, the manipulation associated with this procedure does not have a signficant effect on the result of cytology. In the case of positive UUT cytology results, ureteroscopy would be a further option to rule out UUT urothelial carcinoma. Because of studies showing that fluorescence in situ hybridization (FISH) might have a role as an anticipatory positive marker for urothelial carcinoma both in the primary setting and in the follow-up of patients with known bladder cancer. 3 Yoder B.J. Skacel M. Hedgepeth R. et al. Reflex UroVysion testing of bladder cancer surveillance patients with equivocal or negative urine cytology: a prospective study with focus on the natural history of anticipatory positive findings. Am J Clin Pathol. 2007; 127: 295-301 Crossref PubMed Scopus (158) Google Scholar , 4 Skacel M. Fahmy M. Brainard J.A. et al. Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. J Urol. 2003; 169: 2101-2105 Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar and because of its relatively high specificity, we also recommend re-evaluation of patients with negative cystocopy and positive FISH results, especially in the case of a second positive urine marker (immunocytology or NMP22) or risk factors for urothelial carcinoma (such as smoking). For uCyt, we do not have a clear recommendation because of the relatively high variability of reported specificities. 5 Budman L.I. Kassouf W. Steinberg J.R. Biomarkers for detection and surveillance of bladder cancer. Can Urol Assoc J. 2008; 2: 212-221 PubMed Google Scholar In patients with isolated increased NMP22 and negative cystoscopy results, the low specificity, especially in the context of mechanical manipulation, urinary tract infection, and hematuria, does not justify further invasive measurements. However, the predictive role of positive urine markers has to be evaluated in larger studies to make clear recommendations, especially in the follow-up of patients with urothelial carcinoma. We also agree that aggressive work-up because of positive urine markers in patients without symptoms or risk factors for urothelial carcinoma should be avoided. Given our experience with these markers, we do not agree that further workup for isolated urine markers, especially in the case of present hematuria and positive FISH, cytology and uCyt, results “never reveals any malignant abnormality.” Editorial CommentUrologyVol. 79Issue 3PreviewThe authors have written a straightforward paper describing the false-positive rates for different urinary markers depending upon whether the urine samples were simply voided or were collected after instrumentation, as well as whether there was any evidence for inflammation at time of collection. Some of the markers were quite resistant and their sensitivities/specificities did not change much, whereas for others—specifically NMP22—their utility drops precipitously. Full-Text PDF