UroToday - Detection of chromosomal abnormalities using fluorescence in situ hybridization (FISH) has become an integral tool in the surveillance of urothelial carcinoma. FISH has proven particularly useful in clarifying cases of equivocal cytology and has sufficient predictive capability to tailor surveillance and treatment regimens for individual patients. The prognostic significance of a positive FISH test (defined as a gain of ?‰?2 chromosomes (3, 7, or 17) in 4 cells, isolated loss of 9p21 in 12 cells, or isolated gains of only 1 chromosome in ?‰?10% of cells) is well documented, with the majority of FISH+ patients developing recurrent disease within one year of the positive result. As such, patients with a positive FISH result are likely to be directed towards more aggressive follow-up and treatment regimens.

In contrast, the current literature lacks data on outcomes for patients who demonstrate equivocal changes on FISH testing, i.e., fewer than four gains of chromosomes 3, 7, or 17 in ?‰¤3 cells. Clinicians and patients alike may still associate such non-diagnostic results with a greater risk of malignancy despite the absence of supporting data. In the current study, we sought to determine the clinical significance of non-diagnostic FISH results in a population of patients previously diagnosed with UC by characterizing the likelihood of subsequent disease recurrence (marked by progression to a positive FISH or development of a bladder tumor) following a non-diagnostic FISH test.

We performed a retrospective review of bladder UC patients and initially found an increased risk of disease recurrence among patients with a non-diagnostic FISH compared to those who had a truly negative result. However, after controlling for cytologic and cystoscopic findings, patients with non-diagnostic and negative FISH results had comparably low risks of progression to positive FISH or developing a bladder tumor.

Our data suggest that a non-diagnostic FISH result by itself is not a premalignant marker and does not justify more aggressive follow-up or a lower threshold for intervention. In the absence of positive cytologic or cystoscopic findings, a non-diagnostic FISH can be considered equivalent to a truly negative result.

Written by Carvell T. Nguyen, MD as part of Beyond the Abstract on UroToday

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