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Apical Urinary Bladder Transitional Cell Carcinoma in a Dog

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Ashe is a 9-year-old female spayed Siberian Husky that was presented to the oncology service for a recent diagnosis of urothelial transitional cell carcinoma (TCC).

Ashe had initially presented to her primary care veterinarian for pollakiuria and hematuria. A urinalysis was performed and revealed a urine pH of 7.5, mild proteinuria, white blood cells 21-50/high power field (hpf), red blood cells 4-10/hpf, and bacteruria, rods 51-100/hpf. She was treated for a urinary tract infection with cefpodoxime 8 mg/kg/day. She was later presented for an abdominal ultrasound which revealed a broad-based cranial urinary bladder mass measuring 1.4 cm x 0.9 cm. A urine BRAF mutation test (CADET® BRAF, Antech Diagnostics, Inc.) was submitted, which detected a BRAF mutation in Ashe’s urothelial cells and confirmed a diagnosis of urothelial carcinoma.

Upon presentation to the Pet Specialists of Austin oncology service, staging thoracic radiographs were recommended prior to starting therapy. No evidence of pulmonary metastasis was reported. It was recommended that Ashe initially undergo a partial cystectomy to remove the bulk of the urinary bladder mass, followed by a course of adjuvant vinblastine chemotherapy. Histopathology of the bladder mass further confirmed a diagnosis of TCC in situ. Two-weeks following the partial cystectomy, a repeated monitoring urine CADET® BRAF mutation test showed that there was no longer a BRAF mutation detectable. Ashe was initiated on a planned course of 8 bi-weekly doses of adjuvant vinblastine chemotherapy. It was also recommended to perform re-staging thoracic radiographs and abdominal ultrasounds every 2-3 months to monitor for tumor recurrence or progression. The client also elected to have repeated CADET® BRAF mutation testing performed at the re-staging visits.

Ashe tolerated the initial four vinblastine treatments well without any reported adverse events, and her urinary symptoms completely resolved within a month of having the partial cystectomy. Upon re-staging 2 months following the partial cystectomy, abdominal ultrasound revealed a 0.6 cm focal thickening with mineralization at the dorsal aspect of the urinary bladder. A repeated CADET® BRAF mutation test at that time also showed that a BRAF mutation was again detectable. Although the ultrasound findings were subtle and could not definitively diagnosis tumor recurrence, the findings of the BRAF mutation testing prompted a change in therapy.

Ashe was then enrolled in the FidoCure® program and prescribed two compounded molecular targeted therapies, the MEK inhibitor trametinib and the multi-tyrosine kinase inhibitor lapatinib. Ashe has continued to receive these therapies, and re-staging thoracic radiographs and abdominal ultrasound have not identified any tumor progression for over six months. Monitoring CADET® BRAF testing has shown a decrease in the fraction of BRAF mutation positive cells.

This case highlights some unique aspects of diagnosis and treatment of urothelial TCC in the dog. First, apical urinary bladder masses previously were difficult to diagnose without a tissue biopsy. More recently, the use of the CADET® BRAF test has become a non-invasive tool to diagnose and monitor treatment response to canine urothelial cell carcinomas (Mochizuki H, et al. PLoS One 2015). Second, majority of canine urothelial TCC cases that are presented are not candidates for surgical removal of urothelial masses due to tumor location in either the trigone or urethra. In cases of apical urinary bladder masses, it has been reported that dogs may have improved outcomes if a partial cystectomy is performed (Marvel SJ, et al. Vet Comp Oncol 2017). Lastly, the use of targeted therapies may become more prevalent for treatment of canine tumors with a confirmed mutation status.

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