Beyond the Abstract - Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer, by Fabio Campodonico, MD and Egi Edward Manuputty, MD

BERKELEY, CA (UroToday.com) - The UroVysion® kit for urinary FISH was introduced into daily practice a few years ago.

The test is based on a simple collection of one sample of fresh urine processed for biomolecular analysis. The test focuses on the presence of one or associated among four chromosomal abnormalities (ch 3,7,17 and locus 9p21) in cells exfoliated from the urinary tract. FISH has shown promising results as a marker for surveillance in superficial bladder cancer.(1) In our previous experience (2) we found a superior sensitivity of FISH compared to cytology in low grade and low stage bladder cancer, but these tumors today can also be managed with active surveillance due to its intrinsic indolence to progression.(3)

 

However a more interesting and recent application of FISH is as a prognostic marker in the follow-up of bladder cancer. Mian, et al.(4) characterized the behavior of superficial bladder cancer into two patterns of risk groups based on FISH test results; the low-risk group associated with aberrations of chromosome 3 and/or locus 9p21; and the high risk-group for chromosome 7 and/or 17. They found a median time to recurrence was 16.7 months in high-risk vs. 30.8 months in low-risk patients, and progression of disease was observed in 50% of high-risk as compared to 11% of low-risk patients.

In our study, patients with histories of superficial bladder cancer, excluding those with previous or later diagnosis of Tis, were divided into low and high-risk groups according to the chromosomal alterations described above. One single FISH test performed at a non-specific time of follow-up was the main inclusion criteria. The aim of the study was to evaluate the courses of these patients in terms of clinical events such as recurrence or progression. A group of 126 patients was followed for a median of 14 months (range 1.5 to 59) with 46 patients (36.5%) experiencing recurrence. In 76 FISH positive patients, the hazard ratio (Cox model) for disease recurrence or progression was 1.6 in low-risk patients and 1.9 in the high-risk group. Among the 27 high-risk patients eight of them finally underwent cystectomy, while of the 53 negative FISH test patients, two cystectomies were performed in three patients shifted to the high-risk pattern afterward. In patients with baseline negative FISH, their test results converted to be positive before recurrence. In terms of patient management , this means that the high-risk group (marked with ch 7 or/and 17 or full aberrations) is more prone to a significant clinical event such as early tumor recurrence or progression. Thus these patients should be more strictly followed and provided with individualized treatment if necessary. Moreover, in patients assigned to management with intravesical chemotherapy or BCG, performance of the FISH test after a treatment cycle can represent an additional prognostic tool based on the risk of chromosomal pattern.(5) This quantitative information should optimize the simple value of positive or negative cytology. In our clinical practice we use urinary FISH as a marker for risk stratification in selected patients for further clinical decision-making.

References:

  1. Laudadio J, Keane TE, Reeves HM, Savage SJ, Hoda RS, Lage JM, Wolff DJ: Fluorescent in situ hybridization for detecting transitional cell carcinoma: implications for clinical practice. BJU Int 2005; 96:1280-1285.
  2. Capponi G, Casazza S, Campodonico F, Bandelloni R, Maffezzini G: A prospective comparison using flurescence in situ hybridization and cytology. Eur Urol Suppl 4;2005, Abstract 470
  3. Gofrit ON, Shapiro A: Active surveillance of low-grade bladder tumors. Arch Ital Urol Androl 2008;80:132-135.
  4. Mian C, Lodde M, Comploj E, Lusuardi L, Palermo S, Mian M, Maier K, Picha A: Multiprobe fluorescence in situ hybridization: prognostic perspective in superficial bladder cancer. J Clin Pathol 2006;59:984-987.
  5. Kipp BR, Karnes RJ, Brankley RM, Harwood AR, Pancratz VS, Sebo TJ, Blute MM, Lieber MM, Zincke H, Halling KC: Monitoring intravesical therapy for superficial bladder cancer using fluorescence in situ hybridization. J Urol 2005;173:401.404.

 


Written by:
Fabio Campodonico, MD and Egi Edward Manuputty, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Urology, Ospedale Galliera, Genova, Italy


Prognostic significance of fluorescent in situ hybridisation in the follow-up of non-muscle-invasive bladder cancer - Abstract

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