An update on diagnosing and treating urinary bladder transitional cell carcinoma in dogs
Transitional cell carcinoma of the urinary bladder is by far the most common neoplasm of the urinary system in dogs. Less common histologic types of urinary system tumors include rhabdomyosarcoma, squamous cell carcinoma, adenocarcinoma, and various other mesenchymal tumors.1,2 Canine urinary system tumors most commonly occur in the bladder and proximal urethra; transitional cell carcinoma in dogs occurs most frequently at the bladder trigone. Consequently, transitional cell carcinoma may eventually lead to partial or complete obstruction of the urinary outflow as the tumor progresses. In male dogs, invasion into the prostate is common and is associated with a poorer prognosis.3
The aim of this review is to familiarize practitioners with the common clinical presentations of bladder transitional cell carcinoma in dogs as well as to describe current and future diagnostic tools and treatment options.
ETIOLOGY AND PATHOLOGIC CHARACTERISTICSSeveral breeds, including Scottish terriers, Shetland sheepdogs, beagles, and West Highland white terriers, appear overrepresented for developing bladder transitional cell carcinoma. Of these breeds, Scottish terriers have the highest risk, with an approximately 19-fold increased odds ratio compared with mixed-breed dogs.3 But there is no known association between a dog's breed and the tumor's biologic behavior or response to therapy.
Female dogs are about twice as likely to develop bladder transitional cell carcinoma than are male dogs.1 One proposed reason for this gender disparity is that male dogs, in the process of territorial marking, urinate more frequently, which decreases the contact time of potential carcinogens with the urothelium.
Exposure to phenoxy herbicides has been linked to a significantly increased risk for the development of bladder transitional cell carcinoma in Scottish terriers.4 However, the newer topical insecticides such as fipronil and imidacloprid do not appear to elevate the risk of transitional cell carcinoma in this breed.5
The alkylating agent cyclophosphamide is known to increase the risk of bladder cancer ninefold in people and could play a similar role in dogs, although documented cases of transitional cell carcinoma developing in dogs after cyclophosphamide therapy for other malignancies are scarce.3,6,7
Additional risk factors for developing transitional cell carcinoma include obesity, possibly owing to adipose tissue serving as a storage area for carcinogens, and living near marshes sprayed with insecticides for mosquito control.8 Interestingly, no increased risk for developing transitional cell carcinoma was observed in dogs exposed to second-hand smoke in one study.8 But in people, a direct correlation exists between the number of cigarettes smoked daily and a higher risk for bladder transitional cell carcinoma.9
In dogs, bladder transitional cell carcinomas are typically locally infiltrative papillary carcinomas, and more than 95% have intermediate to high histologic grades; low-grade and in situ carcinomas are less common.2,3 Like most aggressive solid tumors, transitional cell carcinomas are highly vascular.10 The concentration of basic fibroblastic growth factor, a potent proangiogenic molecule expressed in many cancers,11 was recently found to be elevated in the urine of dogs with transitional cell carcinoma when compared with the urine of dogs with nonneoplastic lower urinary tract diseases, and these concentrations decreased in response to piroxicam therapy.12 This finding suggests a potential role for basic fibroblastic growth factor in the progression of canine transitional cell carcinoma and supports angiogenesis as a potential therapeutic target.
The inducible isoform of cyclooxygenase, COX-2, has generated a lot of interest in oncology in the last decade. Through its primary downstream metabolite prostaglandin E2 (PGE2), COX-2 can promote angiogenic factor recruitment, decrease immune surveillance, increase tumor growth and invasiveness, and reduce apoptosis.13 Overexpression of COX-2 has been demonstrated in numerous cancer types, including transitional cell carcinoma in dogs. In one study, COX-2 immunoreactivity was identified in all of 21 canine transitional cell carcinoma samples evaluated, but normal bladder epithelium did not demonstrate COX-2 immunoreactivity.14 It appears that COX-2 overexpression may play an important role in the development and progression of transitional cell carcinoma in dogs, and its inhibition is clearly a potential therapeutic target.