Presented October 25th - 28th, 2007 at the 2007 Urological Research Society (URS) Meeting - Napa, California

Introduction: (1) To study the possibility of pre-clinical testing of intravesical therapies against non-muscle invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model. (2) To study the value of the use of serial cystoscopy for in vivo tumour assessment and follow-up

Methods: The bladder mucosa of Fischer F344 rats was conditioned with an acid rinse through a 16-gauge transurethral cannula, followed by a 1-hour instillation of 1.5 x 10⁶ AY-27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control), 3, 4, 5, 6, 7, 10, 13 and 17. At predestined time points cystectomy was performed and rats were sacrificed (n = 4/time point) for microscopic examination of the bladder.

Results: Overall tumour formation was >80% with predominantly carcinoma in situ preceding invasive tumour growth or concomitant to invasive tumour growth. All tumours were formed from day 3-5, and remained non-muscle invasive up till day 5. From day 6 on, tumours progressed to muscle invasive disease in 40% of animals. Visibility at cystoscopy was excellent and tumours were seen in >90% of rats from day 5 on, with specificity and sensitivity >90%. Cystoscopy could not distinguish NMIBC from muscle invasive disease.

Conclusions: This orthotopic rat bladder UCC model is reliable, with early high grade NMIBC growth, immediately followed by muscle invasive growth. The recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle invasive bladder cancer.

Authors: Witjes JA, Hendricksen K, Molkenboer-Kuenen J, Oosterwijk E, Hulsbergen-van de Kaa CA

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