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| The urinary tract in dogs includes the kidneys, ureters, urinary bladder, prostate, and urethra. Cancer can occur in any of these sites but the bladder is most commonly affected. Although bladder cancer in dogs accounts for approximately 1% of all dog cancers, the rate of increase of this type of cancer over the past 10 years is estimated at over 200%. The most common type of bladder cancer is invasive transitional cell carcinoma (TCC). TCC is a malignant tumor that invades the deeper layers of the bladder wall. It usually involves the neck of the bladder in the area called the trigone. Both ureters from the kidneys dump their urine into the bladder in the trigone area which can cause obstruction in the flow of urine. TCC can also metastasize to lymph nodes and other organs in the body (lung, liver, etc.). TCC is most often found in the bladder, but can also develop in the kidneys, ureters, prostate, and urethra. This form of cancer is almost identical to the higher grade, invasive form of bladder cancer found in humans. TCC generally has a poor prognosis because the disease is usually diagnosed when it is quite advanced. |
| Definition |
| Bladder Cancer |
| The exact cause of cancer in any dog usually can not be pinpointed exactly. In general however, TCC can be linked to several factors including genetic predisposition, environmental influences such as lawn chemicals and aromatic hydrocarbons (paraaminobiphenyl, paranitrioliphenyl, betanapthylamine), and flea & tick dips and shampoos. A genetic link is suspected because TCC is more common in specific breeds of dogs, including Scottish Terriers (18x increased risk compared to other breeds), Shetland Sheepdogs (4x increased risk), Beagles (4x increased risk), West Highland White Terriers (3x increased risk), and Wire Hair Fox Terriers (3x increased risk). Environmental factors include pesticides, insecticides, and flea & tick products. Some scientists believe that it is not the active ingredients in the flea and tick products that cause bladder cancer, but rather the inert ingredients that serve as solvents for the active ingredients. They include know carcinogens such as benzene, toluene, xylene, and petroleum distillates. Because the greatest cause of TCC in humans is smoking, it is hypothesized that second hand smoke may also contribute to TCC in dogs. Purdue University conducted a study of the risks of exposure to herbisides and flea & tick products to bladder cancer in Scottish Terriers. Read the fascinating full report at http://www.vet.purdue.edu/epi/canblad.htm |
| Causes |
| Bladder cancer risk factors include a genetic predisposition and exposure to herbisides, pesticides, and second hand smoke. Most cases of TCC occur in dogs older than 7 years old. Females and overweight dogs appear to have a statistically higher risk of developing the disease. One explanation of the gender differences in developing bladder cancer in dogs is that males urinate more frequently than females, giving the carcinogens more contact time with the bladder in females. Another explanation is the females have relatively more body fat and the chemicals which are known to cause bladder caner are stored and concentrated in fat. This also explains why obese dogs are more likely to develop the cancer. Exposure to the drug cyclophosphamide, used to treat cancer and some immune-mediated diseases, and its carcinogenic breakdown product (acrolein) has been suspected in development of bladder cancer. Dogs that have been treated with this drug should be monitored for potential signs of bladder cancer like blood in the urine, straining to urinate and increased frequency of urination. |
| Risk Factors |
| Symptoms |
| TCC in dogs presents with symptoms such as blood in the urine (urinating cots or blood stained with urine) and straining to urinate. Urinary tract infections will often have these same symptoms which may delay the diagnosis of cancer if that is truly the cause of these symptoms. Some TCC cases present with lameness due to spread of the tumor into the bones. The most common symptoms include:
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| Diagnosis |
| Treatment |
Treatment options include:
For dogs diagnosed with TCC, surgery may be an option if the cancer is found in small masses confined to the fundus or body. However, if the cancer is located near the neck of the bladder or the urethra, then surgical excision is not recommended because several important structures in the neck of the bladder (junction with ureters and urethra, urethral sphincter) are in this location. In addition, in order to remove the tumor with “clean margins”, a surgeon must remove not only the tumor itself, but also non-infected tissue surrounding it and this is not often possible once the tumor has invaded the bladder walls. If microscopic cancer cells are left behind in a malignant cancer like TCC, then the cancer will likely recur. Because most TCCs are found in dogs are invasive into the bladder wall and located in the neck of the bladder, surgical removal is not advised. It has not yet been determined if there is a benefit from removing part of the tumor in dogs in which the entire tumor cannot be removed. Radiation therapy can be used to treat some bladder cancers by directing a beam of radiation at the affected area and sites of metastasis. It has been used to successfully control TCC growth in the bladder in some dogs. Unfortunately, radiation of the bladder can cause adverse effects including a scarred, shrunken bladder, and irritation to surrounding organs. Therefore, the majority of TCC cases are treated with medication therapy. The two categories of drugs that have been used to treat TCC include traditional chemotherapy (including cisplatin, carboplatin, adriamycin, and mitoxantrone), and nonsteroidal antiinflammatory drugs (NSAIDs). These drugs are often very toxic, resulting in adverse effects such as bone marrow suppression leading to low white cell count, gastrointestinal toxicity with nausea and vomiting, and kidney toxicity. Remissions of six months and sometimes longer have been achieved with chemotherapy. NSAIDs have been used more successfully. These drugs block the cyclooxygenase (cox) enzyme, and are also referred to as “cox inhibitors”. Cox inhibitors include piroxicam (Feldene®), aspirin, ibuprofen, naproxen, and others. Oncologists at Purdue University became interested in piroxicam when it was being used for pain relief in dogs with cancer, and unexpected remissions occurred. Two of the first dogs treated (one with metastatic carcinoma, one with undifferentiated sarcoma) had advanced cancer, and these dogs had remission of their cancer when only receiving piroxicam. This has led to numerous studies of piroxicam in animals with cancer at Purdue. In 62 dogs with TCC treated with piroxicam, the tumor went into complete remission in 2 dogs, decreased in size by > 50% in 9 dogs, remained "stable" in size (<50% change) in 35 dogs, and increased in size by > 50% in 16 dogs. The median survival (195 days) compared favorably to survival with chemotherapy in other studies. In an attempt to improve the response of TCC to therapy, oncologists at Purdue University conducted a study comparing chemotherapy (cisplatin) alone to chemotherapy plus piroxicam. In this study the combination of cisplatin and piroxicam was more effective against the cancer, but the combination treatment caused a rise in the urea level in a blood test, indicating it is toxicity to the kidneys. Combining piroxicam with other chemotherapies has not been as successful. Currently, oncologists at Purdue University are conducting a study of cisplatin chemotherapy combined with a newer type of cox inhibitor (cox-2 inhibitor) with the expectation that tumor remission will occur with less toxicity from the treatment. Cox-2 inhibitors are expected to cause less side effects to the stomach and intestinal tract and to the kidneys. Cox inhibitors like piroxicam have few side effects. However some will have stomach or intestine irritation. Therefore, if a dog on piroxicam has loss of appetite, vomiting, or dark tarry-looking stools, it is safest to stop the piroxicam and consult the veterinarian before starting the medication again. The new cox inhibitors, selective cox-2 inhibitors, are not expected to cause stomach irritation as frequently as piroxicam does. Dogs with TCC are very prone to developing bacterial infection (cystitis) in the bladder. Therefore, frequent urinalysis, culture, and treatment with antibiotics may be necessary. TCC can also block the flow of urine into and out of the bladder. If the flow of urine out of the bladder is blocked, a cystotomy tube (small diameter tube that goes from the bladder through the wall of the abdomen to the outside) can be placed to allow emptying of the bladder. Complete obstruction can rapidly lead to a build up of urea and life- threatening complications. The tube can be used to "void" urine when the urethra is blocked. It is important for dog caretakers to observe their dog to be sure he/she is able to pass the urine. Signs to watch for that may indicate that cancer has progressed or spread include: straining to urinate or defecate, decreased activity, shortness of breath, coughing, and decreased appetite. |
| Prognosis |
Factors that negatively affect survival time include more extensive tumor within the bladder, spread of tumor beyond the bladder, and involvement of the tumor in the prostate gland. Approximately 20% of dogs with TCC have detectable metastasis at diagnosis, and 50% have metastasis at death. Longer survival times have been reached when chemotherapy is combined with piroxicam, but the optimal combination treatment is still under investigation. |
| Diagnosis of TCC is complicated by the fact that the clinical signs often mimic those of a urinary tract infection. Several other types of growths in the bladder, bladder stones, or bladder inflammation can also cause similar symptoms as TCC. Some of these other conditions can also cause what appear to be masses on radiographs or ultrasound or can cause abnormal cells in the urine, which can be mistaken for TCC. Therefore, to definitively diagnose urinary bladder cancer and stage the disease for treatment and prognosis purposes, a tissue biopsy will be required. Other non-cancerous conditions of the bladder include: Cystic calculi (bladder stones). Bladder stones are relatively common in dogs and cause signs similar to those seen with bladder cancer. Bladder stones irritate the lining of the bladder blood in the urine, straining to urinate and increased frequency of urination. Benign tumors of the bladder. Polyps and other benign growths such as leiomyomas, which are benign tumors of smooth muscle, can occur in the bladder but are quite rare. Such masses may be removed by surgery and do not usually return. Tests that may be performed to provide an accurate diagnosis of bladder cancer and prognosis include:
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