Assessing the value of reflex fluorescence in situ hybridization testing in the diagnosis of bladder cancer when routine urine cytological examination is equivocal

Purpose: We evaluated the usefulness of fluorescence in situ hybridization in the treatment of patients with equivocal cytology. Materials and Methods: Fluorescence in situ hybridization was performed in residual urine from 124 patients with a cytological diagnosis of cell clusters (22), atypical findings (46) and suspicious findings (56) who had a same day cystoscopy result and bladder biopsy within 6 months of the cytology diagnosis. Urologists and fluorescence in situ hybridization technologists were blinded to the matching fluorescence in situ hybridization and cystoscopy results, respectively. Results: In conjunction with cystoscopy fluorescence in situ hybridization was significantly more sensitive than cystoscopy alone for detecting cancer (87% vs 67%, p<0.001) and muscle invasive cancer (94% vs 56%, p=0.031). Of the 124 equivocal cytology specimens 58 (47%) were positive by fluorescence in situ hybridization. Of these patients 53 (91%) had subsequent evidence of carcinoma, including Ta tumors in 17, Tis in 13, T1 in 8 and T2 or greater in 15, on the first followup biopsy. Three of the 5 remaining patients with a positive fluorescence in situ hybridization result and negative first followup biopsy had evidence of cancer at a later date, including TxN+ disease in 2 and Tis in 1. A total of 66 specimens were diagnosed as negative by fluorescence in situ hybridization. Of these patients 34 (52%) had negative biopsy results, whereas the remaining 32 (48%) demonstrated bladder cancer, including Ta disease in 20, Tis in 8, T1 in 2 and T2+ in 2. Cystoscopy detected 21 of the 32 tumors (66%) not detected by fluorescence in situ hybridization, while fluorescence in situ hybridization detected 17 of the 28 (61%) not detected by cystoscopy. Conclusions: Our data suggest that fluorescence in situ hybridization with cystoscopy can aid clinicians in the diagnosis of bladder cancer in patients with equivocal cytology.