Should we abandon the FISH test

Bladder cancer is the fourth most common malig-nancyinAmericanmen.In2006,>60,000menwillbediagnosedwithbladdercancer,ofwhomthemajoritywill present with non–muscle-invasive disease [1].Most patientsareinitiallydiagnosed after anepisodeofgrosshematuria;fewarediagnosedduringroutinescreening for microscopic hematuria. The AmericanUrologic Association Best Practice Guidelines for theevaluation of microscopic hematuria recommends afull urologic work-up for all high-risk patients orthose with two or more documented positiveurinalyses [2]. Each evaluation consists of an uppertract imaging study, cystoscopy, and cytology.Although the trained urologist should easily be abletoidentifyanysignificantpapillaryorsessilelesioninthe bladder, the identification of carcinoma in situ(CIS)canbemoredifficult.Classicallydescribedasanerythematous, velvety patch of abnormal mucosa,CIS can be missed by the urologist if the bladder isover- or under-distended, if the bladder mucosa isedematous from an indwelling catheter, or if theentire bladder is not completely visualized. Theaddition of cytology is thus to aid the urologist indiagnosing CIS and to indicate any other high-gradetumorsthatmaybemissed.Cytologyisnotnecessaryto identify low-grade papillary lesions because theycan be identified cystoscopically and if missed are oflittle or no risk to the patient. Although voidedcytology does not detect all urothelial tumors, thesensitivity for high-grade urothelial carcinoma (UC)approaches 90% [3]. If bladder wash cytology is used,the sensitivity may be improved [4,5].Recently, FISH (Urovision) has been approved bythe Food and Drug Administration and marketed asan adjunct to cytology. The test is an assay intendedto detect aneuploidy for chromosomes 3, 7, and 17and loss of the 9p21 locus via fluorescence in situhybridization (FISH). The test is approved as an aidfor initial diagnosis of bladder carcinoma in patientswith hematuria and subsequent monitoring fortumor recurrence in patients previously diagnosedwith bladder cancer. A pivotal multicenter studyreported that the overall sensitivity of FISH com-pared to voided urine cytology was 71% and 26%,respectively [6]. Most importantly, the sensitivity ofFISH for CIS and grade 3 lesions was 100% and 94%,respectively.Otherstudiesprovidesimilardata[7,8].Although the sensitivity of FISH is higher thancytology if all stages and grades of bladder cancerare included, suggesting an advantage for clinicalpractice, the modest benefit in sensitivity for high-grade UC comes at a price. A recent comprehensivereview of urine markers by van Rhijn et al reported amedian specificity for FISH of 70% compared to 94%for cytology [9]. Moreover, Sarosdy et al maintainedthat the specificity of FISH is partially related to‘‘anticipatory positives’’: patients with a positiveFISH and negative cystoscopy and cytology, whosubsequently develop a bladder tumor [6]. However,93% of the ‘‘anticipatory positives’’ had a low-gradeTa tumor, and these tumors were seen at a mean of6 mo and were potentially missed on the initialevaluation and not true recurrences. The results of aFISH are not ‘‘black and white’’; the test requires a