Urinary Bladder Cancer

Deborah W. Knapp, West Lafayette, Indiana

Canine Urinary Bladder Tumors

Urinary bladder cancer comprises approximately 2% of all reported malignancies in the dog. With the pet dog population in the United States exceeding 70 million, this translates into several thousand cases of urinary bladder cancer annually.

Transitional cell carcinoma (TCC) is the most common form of canine urinary bladder cancer (Knapp, 2006, 2007). The vast majority of dogs with TCC have papillary infiltrative cancer of intermediate to high grade. TCC most often is located in the trigone region of the bladder. Papillary lesions and bladder wall thickening can lead to partial or complete urinary tract obstruction. In a series of 102 dogs with TCC, the tumor involved the urethra (as well as the bladder) in 56% of dogs and the prostate in 29% of male dogs (Knapp, 2007). TCC metastasizes to distant sites in approximately 50% of cases. Sites of metastasis include regional lymph nodes, lung, liver, spleen, and, less commonly, kidney, bone, and other organs.

The clinician should not assume that all bladder masses are TCC. Mass effects in the bladder can occur with polyps, other inflammatory lesions, and other tumor types. The latter can include squamous cell carcinoma, adenocarcinoma, undifferentiated carcinoma, lymphoma, rhabdomyosarcoma, hemangiosarcoma, fibroma, and other tumors.

Cause and Possible Prevention Strategies

The cause of canine bladder cancer is multifactorial. Risk factors include exposure to older-generation flea-control products (dips, powders, sprays), herbicides, insecticides, and possibly cyclophosphamide; obesity; female gender (female : male ratio, 1.7 : 1 to 1.95 : 1); and breed (Knapp, 2006, 2007). Breeds with increased risk of TCC are listed in Table 83-1.

TABLE 83-1

Breed and Risk of Urinary Bladder Cancer in Pet Dogs (Summary Data From Veterinary Medical Database)*

Breed	Odds Ratio	95% Confidence Interval
Mixed breed	1.0†
All pure breeds	0.74	0.62-0.88
Scottish terrier	19.89	7.74-55.72
West Highland white terrier	5.31	2.51-11.63
Shetland sheepdog	4.46	2.48-8.03
Beagle	4.15	2.14-8.05
Wirehaired terrier	3.20	1.19-8.63
Miniature poodle	0.86	0.55-1.35
Miniature schnauzer	0.92	0.54-1.57
Doberman pinscher	0.51	0.30-0.87
Labrador retriever	0.46	0.30-0.69
Golden retriever	0.46	0.30-0.69
German shepherd	0.40	0.26-0.63

^*Updated from results published previously (Knapp, 2007).

^†Reference category.

Knowledge of the risk factors for TCC can be used to take steps that can reduce TCC risk or allow earlier detection if TCC develops. The owners of dogs in high-risk breeds should be informed of the risk and the clinical signs of TCC (hematuria, stranguria, inappropriate urination) and encouraged to seek timely veterinary care should these signs occur. Although it would appear appropriate to perform some form of TCC screening in older at-risk dogs (e.g., periodic urinalysis with sediment examination, abdominal ultrasonography), the benefit of this has not yet been determined. There is evidence that limiting exposure to lawn chemicals and older types of flea products can be important in reducing TCC risk, especially in dogs in high-risk breeds. A significant association between herbicide exposure and TCC was identified in a case-control study in 166 Scottish terriers (Knapp, 2007). TCC risk was sevenfold higher (odds ratio, 7.19; 95% confidence interval, 2.15 to 24.07; P < .001) in dogs exposed to lawns or gardens treated with herbicides and insecticides than in dogs not exposed to these chemicals. An earlier case-control study of dogs of several breeds demonstrated the risk of older types of flea-control products (e.g., flea and tick dips). In the highest-risk group (overweight female dogs), the risk of TCC was 28 times that in normal-weight male dogs not exposed to the insecticides. It is important to note that the newer spot-on types of flea-control products appear safer. In a case-control study in Scottish terriers, spot-on products containing fipronil were not associated with increased risk of TCC (Knapp, 2007). In addition to avoiding certain exposures, adding vegetables to the diet can reduce TCC risk. In a study in Scottish terriers, dogs that ate vegetables at least three times a week, along with their normal diet, had a 70% reduction in TCC risk (odds ratio, 0.30; 95% confidence interval, 0.01 to 0.97; P < .001) (Knapp, 2007). The specific types of vegetable with the most benefit could not be determined, but carrots, given as treats, were the most frequently fed vegetable in the study.

Presentation, Diagnosis, and Clinical Staging

Typically, TCC is a disease of older dogs (median age at diagnosis, 11 years), with females affected more often than males. Common clinical signs include hematuria, dysuria, pollakiuria, and, less commonly, lameness caused by bone metastasis or hypertrophic osteopathy. It is important to note that the lower urinary tract signs observed with TCC are similar to those that occur with urinary tract infection or calculi. Factors that raise suspicion of TCC include persistent or recurrent lower urinary tract signs or infection, older age, and high-risk breed.

The physical examination of a dog with possible TCC should include a thorough rectal examination. Findings depend on the dog’s size but could include a thickened urethra, an enlarged or irregular prostate, a trigonal mass, or enlarged lymph nodes. Bladder masses often are not detected on abdominal palpation. Normal physical examination findings do not rule out TCC.

When TCC is suspected, the clinician should pursue testing to (1) make a definitive diagnosis, (2) determine the cancer stage, and (3) assess the overall health of the patient. These tests include complete blood count, serum biochemistry panel, urinalysis, urine culture, thoracic radiography, abdominal ultrasonography, and bladder imaging. Urine should be obtained by free catch or catheter sample and not by cystocentesis, which has been associated with TCC seeding of the needle tract.

A diagnosis of TCC requires histopathologic confirmation. Although neoplastic cells have been reported to be present in the urine of 30% of dogs with TCC, cancer cells often are indistinguishable from reactive epithelial cells associated with inflammation. Urine antigen tests have been found to be sensitive for TCC, but high numbers of false-positive results limit the value of these tests. It is essential to perform histopathologic examination of the abnormal tissues to determine if TCC is present. Methods of obtaining tissue for diagnosis include cystotomy, cystoscopy, and traumatic catheterization. If surgery is performed, great care must be taken to avoid TCC seeding. Similarly, percutaneous biopsy methods (e.g., transabdominal core biopsy or fine-needle aspiration) should be avoided because these can lead to tumor seeding.

Cystoscopy, using either a rigid or a flexible cystoscope, provides a means to visualize the mucosal surface of the urinary bladder and urethra, to determine tumor location and involvement of the ureteral orifices and urethra, and to collect tissues for diagnosis. Placing tissue samples in a histology cassette before processing helps prevent loss of small samples. In a recent study involving 92 dogs, diagnostic samples reportedly were obtained by cystoscopy in 96% of female dogs and 65% of male dogs that ultimately had histopathologically diagnosed TCC (Childress et al, 2011). The recent introduction of a wire basket designed to capture stones during cystoscopy allows collection of larger tissue samples and is expected to increase the yield of diagnostic biopsy samples. Traumatic catheterization to collect tissues for diagnosis also has been performed, but samples usually are small and of limited diagnostic value. Percutaneous biopsy methods can lead to tumor seeding and are best avoided.

Thoracic radiography and abdominal ultrasonography are recommended to look for evidence of metastases. Lymph node and distant metastases were present in 16% and 14% of 102 dogs, respectively, at the time of diagnosis of TCC (Knapp, 2007). Distant metastases were detected in 50% of dogs at the time of death. Tumor stage can be assigned following the World Health Organization clinical staging system for canine bladder tumors (Box 83-1). Abdominal ultrasonography also is useful for detecting ureteral obstruction and hydronephrosis. Such findings could be an indication for the placement of one or more ureteral stents, especially if other therapies do not relieve the urinary obstruction (see Chapter 76).

Box 83-1 World Health Organization Clinical Staging System (TNM) for Canine Urinary Bladder Cancer