Reply by authors.

To the Editor: We read with interest this excellent report by Gayed et al, who determined the cost-effectiveness of using fluorescence in situ hybridization (FISH) assays to determine the need for biopsy in patients with atypical cytology and equivocal or negative cystoscopy. The findings indicated that performing biopsy based on FISH assay in patients with these scenarios was associated with a significant decrease in bladder cancer associated costs. We agree with their conclusion that in bladder cancer the use of the FISH assay is a costeffective method to determine the role of biopsy in patients with atypical cytology and equivocal cystoscopy. However, for those with negative cystoscopy we would like to share our different experience. As the authors report, 6 bladder cancers were detected in 201 patients with negative cystoscopy (2.9%) at a cost of $206,151 ($34,358.50 per cancer) compared to biopsy in none. Assuming none of the 201 patients underwent FISH assay, $206,151 would be saved, 34 biopsies would be avoided and unnecessary complications related to the procedure could be potentially decreased. If frequent cystoscopy were performed as the guidelines recommend, the diagnoses of the 6 bladder cancers were just postponed rather than missed, and repeat cystoscopy at 3 months likely would have prevented a significant risk of progression. Another noteworthy point is that the FISH assay data from this study were combined from 2 studies with encouraging sensitivity and specificity. FISH assay marks not the presence of a tumor, but the presence of genetically altered or transformed cells in the urine, with the reported performance varying across studies. Therefore, we believe that performing the FISH assay in patients with negative cystoscopy may not be as cost effective as the authors report. FISH is a valuable tool that, when used properly with the right indications, can be of substantial diagnostic value.