Transitional cell carcinoma (TCC) is the most common cancerous condition affecting the urinary tract of dogs. Scottish Terriers top the list in terms of breed predisposition.
What is TCC?
TCC is a malignant tumor that most commonly grows within the urinary bladder. It also frequents the urethra, the tube-like structure that drains urine from the bladder to the outside world. TCC can also arise within the prostate gland (males), kidneys, or ureters (the long, narrow tubes that transport urine from the kidneys into the bladder).
This cancerous growth has a propensity for growing within the trigone region of the bladder, the anatomical area where urinary tract plumbing is most complicated. It is here that the urethra and ureters connect into the bladder. It’s no wonder that TCC commonly causes a dog to experience difficulty urinating and, sometimes, even complete urinary tract obstruction.
What causes TCC?
TCC arises from transitional epithelial cells that line the inner surface of the urinary tract. In addition to growing inward within the lumen of the bladder and/or urethra, the cancer cells invade locally into the walls of these structures. TCC cells also have the ability to metastasize (spread) to lymph nodes and other distant organs.
What are the risk factors of TCC?
Genetic predisposition and environmental factors likely play a role in most cases of TCC. The genetic basis is strongly suspected because Scottish Terriers have as much as an 18-20 fold higher risk of this disease, reports Purdue.edu. Other predisposed breeds include, Shetland Sheepdogs, Beagles, West Highland White Terriers, and Wire Hair Fox Terriers.
Environmental factors that have been incriminated as risk factors for TCC include exposure to older generation pesticides and lawn herbicides. A study comparing 83 Scottish Terriers with TCC and 83 similarly aged, normal Scotties discovered that the group with cancer had greater exposure to lawns and gardens treated with insecticides and herbicides or herbicides alone. The effect of lawn and garden chemicals on other breeds has not yet been studied1.
Smoking is the number one cause of TCC in people, according to cancernetwork.com. It is not known if exposure to second hand smoke contributes to the occurrence of TCC in dogs.
Symptoms of TCC
The earliest symptoms caused by TCC vary from mild to severe, and often resemble those caused by a urinary tract infection. Such symptoms include:
- Increased frequency of urination
- Blood within the urine
- Straining to urinate
- Inability to urinate
Straining to have a bowel movement may be observed if the prostate gland becomes enlarged due to infiltration with TCC cells. When a dog becomes completely unable to urinate due to obstruction, systemic symptoms such as lethargy, vomiting, and loss of appetite will arise within 24 hours.
Diagnosis of TCC
TCC is suspected when a mass within the bladder is detected by an imaging study such as abdominal ultrasound. Growth of TCC within the urethra is best detected via endoscopy (a fiberoptic telescope device that allows visualization within the urinary tract).
Collection of tissue samples from the mass that are then processed and examined under the microscope is the only way to make a definitive diagnosis of TCC. Such tissue samples can be collected via surgery or endoscopy, and sometimes by urinary tract catheterization.
Other TCC testing
Many dogs with TCC have a concurrent urinary tract infection, and a urine culture is performed to determine if antibiotic therapy is warranted.
Once TCC has been diagnosed, “staging tests” may be performed. Staging is the process used to determine if the tumor has spread to other sites in the body. Staging is warranted when the additional information these tests provide are important for providing ongoing care. The results of staging tests assist in:
- Determining the prognosis
- Choosing the most appropriate course of treatment
- Establishing a baseline set of tumor measurements that will help determine if subsequent treatment is successful
- Anticipating which future symptoms may arise
Staging tests for dogs with TCC may include:
- Blood and urine testing
- Radiographs (x-rays) of the chest cavity to look for spread to the lungs and/or lymph nodes
- Ultrasound of the abdomen to assess changes in the kidneys caused by possible obstruction to urine flow and spread of cancer to abdominal organs and/or lymph nodes
Surgical treatment options for TCC
There are several options for treating TCC in dogs. Complete remission (complete elimination) of this cancer is always desirable, but this outcome tends to be the exception rather than the rule. Partial remission (reduction in the overall size of the tumor) and simply arresting growth of the tumor over a prolonged period are far more likely outcomes that usually result in restoring and maintaining an excellent quality of life.
Surgery of TCC
For dogs with TCC that has not spread outside of the bladder, complete surgical removal of the mass is the ideal therapy. Unfortunately, even for a highly gifted surgeon, this outcome usually isn’t possible. This is because TCC has a predilection for growing within the trigone region (neck of the bladder) where aggressive surgery would disrupt the delicate urethral and ureteral plumbing located there. Surgical removal works well when the TCC growth is relatively small and is located well away from the trigone.
Medical therapy of TCC
The medical options described below tend to be extremely well tolerated by most dogs. These drugs may be used individually, but it is not unusual for them to be used in combination to treat dogs with TCC.
Piroxicam is an oral non-steroidal anti-inflammatory medication that substantially reduces the size of many TCC tumors. Piroxicam and other nonsteroidal anti-inflammatory medications (e.g., Rimadyl, Deramaxx, Previcox) are referred to as cyclooxygenase (cox) inhibitors. It so happens that TCC cells often produce and use cyclooxygenase, and inhibition of this enzyme can hinder tumor growth.
Piroxicam’s ability to influence the growth of cancer cells was discovered accidentally when the drug was being used to provide pain relief for dogs with cancer. Unexpected cancer remissions were observed. This resulted in a study of 34 dogs with TCC who were treated with piroxicam2. The results were as follows:
- Complete remission (cancer fully gone): 2 dogs
- Partial remission (cancer reduced in size): 4 dogs
- Stable disease (no change in cancer size): 18 dogs
- Cancer increased in size: 10 dogs
A chemotherapy drug called mitoxantrone has also been used to successfully treat TCC. A study of 48 dogs treated with the combination of piroxicam and mitaxantrone was performed by the Veterinary Cooperative Oncology Group. Results included:
- Complete remission: 1 dog
- Partial remission: 16 dogs
- Stable disease: 22 dogs
- Cancer increased in size: 9 dogs
A third drug for the treatment of TCC is vinblastine. This drug is typically used following failure of the other drugs mentioned above. A study using vinblastine to treat 28 dogs with TCC resulted in3:
- Partial remission: 10 dogs
- Stable disease: 14 dogs
- Cancer increased in size: 4 dogs
Metronomic chemotherapy refers to long term, low dose, frequent oral administration of a chemotherapy drug. Metronomic therapy is given with hopes of blocking the formation of new blood vessels within the tumor, thereby inhibiting its growth. This is referred to as an “anti-angiogenic” effect.
A study of metronomic therapy for TCC was performed using a drug called chlorambucil (Leukeran). Of the 31 dogs studied, 29 had failed prior TCC treatment. The results are as follows4:
- Partial remission: 1 dog
- Stable disease: 20 dogs
- Progressive disease: 9 dogs
- Lost to follow-up: 1 dog
Radiation therapy is an option for control of TCC growth. Unfortunately, applied in suitable dosages, radiation therapy often produces harmful complications affecting the bladder and surrounding organs.
Questions to ask your veterinarian:
- Can my dog’s tumor be completely surgically removed?
- If not, what are the pros and cons of the other treatment options?
- Has a secondary bladder infection been ruled out?
- Has the tumor spread outside of the bladder?
- Can you refer me to a veterinarian who specializes in oncology to further discuss treatment options?
If you have any questions or concerns, you should always visit or call your veterinarian -- they are your best resource to ensure the health and well-being of your pets.
1. Robertson, John, VMD, PhD, and Elizabeth McStay, BS. "Common Health Problems, How to Recognize Them and What to Do About Them." (n.d.): n. pag. Westie Foundation. Web.
Diagnosing Bladder Cancer
- CADET® BRAF – The first test we would choose for diagnosing transitional cell carcinoma (TCC) is the non-invasive CADET® BRAF test. ‘BRAF’ is the name for a gene that, in affected dogs, contains a single mutation indicating TCC. All we need to do is collect 30-40ml of your dog’s urine (over several days) and have it evaluated in a laboratory.
- Cystoscopy – If the first option produces inconclusive results, we can try cystoscopy. A flexible scope is carefully inserted through the urethra and into the bladder while your pet is under anesthesia. We can then examine the urethra and bladder and take tissue samples for biopsy.
- Urine cytology – Urine cytology is a third option where we can examine cells that have been shed into the urine. We can make a correct diagnosis with this test about 30% of the time.
Canine Bladder Cancer
Cancer of the urinary tract in dogs can affect the kidneys, ureters, urinary bladder, prostate, or urethra. In the urinary system, the bladder is affected with cancer most commonly. Compared to cancer in other locations in the body, bladder cancer is unusual, comprising 1-2% of all cancers in the dog.
The most common cancer of the dog urinary bladder is invasive transitional cell carcinoma (TCC) of intermediate to high grade. TCC is a malignant tumor that develops from the transitional epithelial cells that line the bladder. In dogs, this tumor invades into the deeper layers of the bladder wall including the bladder muscles. Canine TCC also has the ability to spread to lymph nodes and to other organs in the body (lung, liver, and other sites). TCC most frequently is found in the bladder, but can also develop in the kidneys, ureters, prostate, and urethra. It can also spread from the bladder into neighboring organs. As a side note: 80% of humans with bladder cancer have a lower grade, less invasive form of TCC, but dogs and cats rarely get this less aggressive form of the cancer.
The exact cause of TCC in an individual dog is usually not known. In general, canine TCC results from a combination of several factors including genetic predisposition and environmental factors. A genetic predisposition is suspected because TCC is more common in specific breeds of dogs, including Scottish Terriers (18 fold increased risk compared to other breeds), Shetland Sheepdogs (4 fold increased risk), Beagles (4 fold increased risk), West Highland White Terriers (3 fold increased risk), and Wire Hair Fox Terriers (3 fold increased risk). Environmental factors identified as risk factors in previous studies have included pesticides, insecticides, and certain dietary factors. The greatest cause of TCC in humans is smoking, but further study is needed to determine the extent to which second-hand smoke may contribute to TCC in dogs.
Blood in the urine and straining to urinate are the most frequent signs of TCC. Pet owners must realize, however, that a urinary tract infection will cause these same symptoms, so the symptoms alone do not necessarily mean their dog has TCC. Less commonly, dogs with TCC can have lameness due to the spread of the tumor into the bones or coughing due to spread into the lungs. To diagnose TCC requires a tissue biopsy. Several other types of growths in the bladder, bladder infection, bladder stones, or bladder inflammation can cause similar symptoms as those in dogs with TCC. Some of these other conditions can cause abnormal cells in the urine, which can be mistaken for TCC. Therefore, diagnosis of TCC requires a tissue biopsy. A tissue biopsy can be obtained by surgery, cystoscopy (insertion of a fiberoptic scope into the bladder and biopsy through the scope), or in some cases with a urinary catheter.
Once a diagnosis of TCC is made, it is important to determine the extent of the tumor, i.e. to perform “tumor staging”. Tumor staging is performed to determine the best way to treat the cancer, to provide some information regarding prognosis, and to establish a baseline tumor measurement in order to determine if treatment is successful. Tumor staging for TCC includes radiographs of the thorax to look for lung metastasis, radiographs and ultrasound of the abdomen to look for metastasis in the abdomen and to assess any changes in the kidneys that result from obstructed urine flow. This information is needed to best plan how to treat the cancer. Also, these tests can be repeated during treatment to know if the treatment is being effective. Approximately 20-30% of dogs have metastasis to “distant” sites such as the lungs, but up to ½ will have “regional” metastasis to the surgical site and nearby lymph nodes.
For dogs with TCC that has not spread beyond the bladder, surgical excision is recommended. In order to surgically excise the tumor, however, it needs to be located away from the neck of the bladder and the urethra. Several vital structures in the neck of the bladder (where these tumors commonly develop) make surgical excision in this location usually difficult, but multiple studies have found that even removing just part of the mass is beneficial for an improved outcome. It is not possible to remove a “margin” of normal tissue around these tumors, except in rare cases, thus microscopic tumor cells are left behind post-op and lead to cancer regrowth.
The vast majority of TCC cases are treated with medical therapy using two drugs: chemotherapy and non-steroidal anti-inflammatories (NSAIDs). Traditional chemotherapy agents include Mitoxantrone, Carboplatin, Adriamycin, Vinblastine, and others have been used in canine TCC. The response with chemotherapy alone has been rather disappointing with
20% of dogs having remission. NSAIDs are also effective in
20% of dogs, but combining chemotherapy with an NSAID will yield response rates of 40-50%. Commonly used NSAIDs include Deramaxx, Piroxicam, Metacam, and Rimadyl. The side effects of chemotherapy are usually tolerable in dogs. Information of specific medications can be discussed with the attending veterinarian.
It is not known how long dogs with TCC that are not treated will live. Survival is affected by the growth rate of the tumor, the exact location of the tumor within the bladder, and whether the tumor has spread to other organs or not. The median survival in dogs treated with chemotherapy or NSAIDs alone is 3-4 months. The median survival time improves to 6-8 months when these therapies are combined. The best prognosis occurs for dogs that have medical therapy following surgery. In patients where minimal tumor remains post-op and they are followed with chemo and NSAIDs, the median survival time increases to 1-1.5 years. If bulky tumor remains post-op, the median survival time is 10-12 months if the patients are followed with chemo and NSAIDs.
Dogs with TCC are very prone to developing a bacterial infection in the bladder. Therefore, frequent urinalysis, culture, and treatment with antibiotics may be necessary. A secondary bacterial infection can result in a sudden worsening in symptoms in dogs with TCC, and these dogs will improve with treatment with antibiotics.
Transitional Cell Carcinoma
What is Transitional Cell Carcinoma?
Transitional Cell Carcinoma (TCC), arising from the transitional cells that line the urinary tract, is the most common tumor of the urinary bladder in dogs and is most frequently located in the trigone region of the urinary bladder (exit of the bladder into the urethra). TCC can affect other portions of the lower urinary tract including the urethra and the prostate (in males). Risk factors that have been described that may increase the risk of developing TCC include sex predisposition (females are at higher risk than males), breed predisposition (Scottish Terriers, Shetland Sheepdogs, Beagles, West Highland White Terriers are overrepresented), obesity, exposure to insecticides and herbicides, and exposure to environmental carcinogens (ie smoking, urban areas).
What are the Clinical Signs?
Clinical signs associated with TCC resemble those of other lower urinary tract diseases. Most owners first notice that their pet has been straining to urinate, urinating more frequently, having bloody urine, and having accidents in the house. The development of frequently recurrent urinary tract infections may also be noted. These clinical signs may be present for weeks to months, and may temporarily resolve with antibiotics, but often recur once the antibiotic is discontinued. Straining to defecate can also occur if the mass or associated lymph nodes enlarge and compress the colon. In some cases, life-threatening complications can occur quickly, related to partial/complete obstruction of the urethra (passage between the urinary bladder to the outside) and can result in non-productive urination characterized by dribbling or an inability to pass urine. Metastatic disease, usually to the regional lymph nodes first and then to the liver, lungs, and bone is typically found in about 15% of cases at the time of diagnosis however, the anticipated metastatic rate of this tumor is estimated to be about 50% over time.
How is TCC Diagnosed and Staged?
The diagnosis of TCC is typically made by the initial discovery of a mass effect in the urinary bladder/proximal urethra on abdominal ultrasound. While this provides information that can be sufficient for a presumptive diagnosis, biopsy, either using traumatic catheterization or transurethral cystoscopy, is the most common means of obtaining a definitive diagnosis and information about grade. If biopsy is not elected, urine sediment cytology looking for the presence of abnormal transitional cells can also be used to support a diagnosis of TCC. A bladder antigen test for canine TCC has been proposed but unfortunately can be falsely positive in urinary tract infections or in the presence of other benign inflammatory conditions.
In addition to tumor sampling, a thorough staging evaluation is recommended including a physical examination, bloodwork, urinalysis, and thoracic/abdominal imaging. A physical examination is recommended to evaluate the urethra, prostate, and regional sublumbar lymph nodes as well to determine if other concerning changes are present. Bloodwork, including a CBC, serum biochemical profile, and urinalysis is also recommended. Additional imaging, including thoracic radiographs and abdominal imaging (typically using abdominal ultrasound), are used to help identify evidence of regional or distant disease spread (metastasis) as well as to assess for urinary tract obstruction affecting the kidneys and ureters.
Urinary bladder TCC is staged using the Tumor, Node, Metastasis WHO Classification:
- T= Primary Tumor: T0= No evidence of cancer (typically achieved after surgical resection if possible), Tis= Carcinoma in situ, T1= Superficial papillary tumor, T2*= Tumor invading the urinary bladder wall, T3*= Tumor invading into adjacent organs
*most primary tumor presentations of canine TCC are T2 or T3
- N= Node: N0= No evidence of regional lymph node metastasis, N1= Regional lymph node involvement, N2= Regional and juxta-regional lymph node involvement
- M= Metastasis: M0= No metastasis, M1= Evidence of distant metastasis
How is TCC Treated?
Surgical Options: Surgical treatment for TCC is regarded as a palliative option or part of a multi-modal treatment approach to TCC. As most urinary TCC primary tumors in dogs are invasive into the bladder wall/adjacent tissue (T2 or T3 presentations) and are primarily located in the urinary bladder trigone or into the urethra, surgical excision is typically not a feasible treatment option without radical approaches (ie removal of entire urinary bladder). In rare cases, surgical excision is plausible (ie apical tumors), however a high risk of local recurrence exists due to a phenomenon called the field effect (locally seeding of the tumor). Instead, surgical techniques involving laser debulking or endoscopically placed urethral stenting are primarily used to palliate the primary tumor and to help immediately address clinical signs associated with lower urinary tract obstruction.
Radiation Therapy: As a single treatment modality, radiation therapy provides poor local tumor control. However, external beam radiation therapy can be used primarily in a palliative setting especially in cases with acute urinary obstruction.
Oral NSAIDS: Non-steroidal anti-inflammatory drugs (NSAIDS), including piroxicam (Feldene) and deracoxib (Deramaxx), have been investigated as single agent therapy for TCC and result in good disease/clinical sign control. These drugs are associated with a
80% disease stabilization, a median disease-free progression of approximately 5-7 months and are frequently used in combination with chemotherapy.
Chemotherapy: Systemic chemotherapy is the preferred treatment of choice for the management of canine TCC. It addresses both the local disease as well as helps reduce the risk of/prolong the time to development of metastatic disease. Mitoxantrone with piroxicam has been associated with a 35% response rate,
80% disease stabilization, median survival times ranging from 8.5 to 11.5 months and is our first line of therapy for these tumors. Other chemotherapeutics that have shown efficacy include the use of doxorubicin, platinum drugs (Cisplatin), gemcitabine, vinblastine, and oral metronomic Leukeran.
Other Options: Photodynamic therapy (PDT) has been used primarily in an academic, investigational setting for the management of canine TCC (particularly for prostatic presentations). Unfortunately, this treatment option is not readily available. Intra-arterial chemoembolization/tumor embolization has been proposed as a possible treatment option for canine TCC, however this has not been evaluated in dogs.
Investigational/Clinical Trial Opportunities: Investigational options and/or clinical trials may be considered if available and if patients are eligible for inclusion.
What is the Prognosis Associated with a Canine TCC?
Prognostic factors associated with canine TCC include:
- Sex (Spayed females are found to have a better survival than castrated males)
- Location and extent of tumor (Poorer prognosis associated with urethral or prostatic presentations or with patients presenting initially with complete urinary obstruction)
- Histologic grade
- Clinical stage (Degree of primary tumor invasiveness and presence of metastasis)
- The use of chemotherapy and type of chemotherapy used (anthracycline antibiotics associated with better outcomes than platinum chemotherapeutics)
Transitional Cell Carcinoma (TCC) in Dogs & Cats
Transitional cell carcinoma is most common neoplasia (cancer) found in the urinary bladder and urethra. These tumors are locally invasive and have a moderate metastatic (spread of cancer) rate. Sites of metastasis can include other regions of the bladder, the local lymph nodes, lungs, bone and other areas.
Signs your pet may experience with this type of cancer include straining to urinate, blood in the urine, frequent urination, thin urine stream including dribbling of urine, pain while urinating and frequent urinary tract infections that may initially respond to antibiotics. In advanced stages, your pet may loose the ability to urinate completely. If in 12 hours, your pet attempts to urinate and no urine is produced, this may be an indication that your pet’s cancer has grown so large that it is obstructing their ability to urinate. When this occurs, it is life threatening. Please seek veterinary care. WVRC is open 24 hours a day for emergencies.
Frequently dogs diagnosed with TCC will experience urinary tract infections. In most cases these require treatment with antibiotics. Sudden worsening of urinary signs may be an indication that your pet has an infection. If this is seen, please take your pet to your family veterinarian or WVRC for physical examination and a (free-catch) urine sample. If your pet has been diagnosed with TCC, never allow your pet to have a needle passed into their bladder, called a cystocentesis, to obtain a urine sample.
As with humans, decreasing exposure to cigarette smoke, keeping fit and eating a well-balanced diet full of fresh vegetables is helpful to prevent cancer. In particular, research has indicated that this is particularly helpful in preventing TCC in our pets. Obesity and exposure to carcinogens, which in the pet includes the “old generation” flea dips and exposure to insecticides and pesticides increase your pet’s risk of developing this cancer. The greatest cause of TCC in humans is cigarette smoke. This has not been fully studied in dogs. Dogs at highest risk of developing this cancer include Scottish Terriers, West-highland White Terriers, Shetland Sheepdogs, Beagles and Wire Hair Fox Terriers.
How to decrease your pet’s risk of TCC:
- Feed your dog a small amount of carrots or cruciferous vegetables daily.
- Keep your pet a healthy weight and go on walks daily.
- Keep your pet off lawns that have been chemically treated and wipe their paws before going inside.
- Decrease your pet’s exposure to cigarette smoke.
If your pet is an at risk breed we recommend screening your pet for cancer after the age of 6 with a urinalysis and an ultrasound of the urinary bladder.
Diagnosis of this cancer type involves getting a tissue biopsy. This is most often done in a minimally invasive procedure called a cystoscopy. This procedure involves passing a narrow camera through the urethra and into your pet’s urinary bladder. This will allow us to assess the extent of involvement and help us to direct the most appropriate treatment. We will obtain a tissue sample for culture and for a biopsy. Results from the biopsy take approximately 1 week to 10 days to return.
In preparation for anesthesia for the cystoscopy, we will perform blood work to check major organ function and x-rays of the heart and lungs to ensure your pet is a good candidate for anesthesia.
If we have a suspicion that your pet may have cancer we will recommend performing tests to determine how far the cancer has spread. This may include x-rays, an abdominal ultrasound, fine-needle aspirates and cytology, a CT-scan, and urinalysis.
The goal of treatment will be to provide your pet with a good quality of life.
SURGERY: In a small percentage of dogs diagnosed with this type of cancer, the cystoscopy will reveal that their cancer is surgically ressectable. If your pet’s cancer is surgically ressectable, the cancer can still seed to other areas of the urinary bladder that was not removed with surgery or to the urethra and may still metastasize (spread distantly). We therefore still highly recommend the use of additional medications which may include non-steroidal anti-inflammatories, which have anti-cancer effects, and/or chemotherapy.
CHEMOTHERAPY: The goal with chemotherapy is to keep your pet’s cancer from growing for as long as possible. There are many chemotherapeutic options available to treat your dog’s cancer and we will often use all of these medications at some point throughout your dog’s care. With treatment, many of our patients can live many months to years with a good quality of life. Unfortunately with no treatment, the average survival time is 2-3 months.
RADIATION THERAPY: The University of Madison Wisconsin has a radiation facility that can irradiate your pet’s cancer. If you are interested in pursuing radiation therapy, we recommend you contact them for further recommendations and appointment options.
PALLIATION: As your pet’s cancer progresses he or she will experience an increased sensation to urinate, causing them to strain. This is often not painful but in a minority of cases, pain medications may help. If your pet’s cancer causes an obstruction a stent can be placed. Although this stent will allow your pet to continue to urinate for a period of time, it needs to be followed with chemotherapy to slow cancer progression.
What are Bladder Tumors in Pets?
Urinary bladder cancer accounts for approximately 2% of all canine cancers. In cats, cancer of the bladder is very rare.
Invasive transitional cell carcinoma (TCC) is the most common type of cancer in the canine bladder. This type of cancer is most often seen in older female dogs, with breeds such as Scottish Terriers and Shetland Sheepdogs topping the list. TCC invades the epithelial lining of the bladder as well as the bladder muscles. This cancer often metastasizes to other parts of the body, and is therefore considered to be quite aggressive. Approximately 50% of the time, the cancer spreads to other parts of the body, including lymph nodes, lungs, liver, and even bones. Signs of TCC can include blood in the urine, straining to urinate, weight loss, and possibly lameness if the cancer has spread to the bone.
The cause of bladder cancer is likely multifactorial. An association between herbicide exposure and TCC in dogs was documented in a study of 166 Scottish terriers. Associations have also been made between the development of TCC and the use of topical flea products and tick dips. Newer spot-on types of flea products appear to be safer.
How is the diagnosis made?
If your pet is exhibiting the pre-mentioned signs, your veterinarian may at first suspect a urinary tract infection and even diagnose and treat one. However, when signs persist through appropriate antibiotic therapy, further diagnostic tests are required. The most useful preliminary test to identify a bladder tumor is an ultrasound. Contrast cystograms are often used, which are radiographs taken after a radiopaque dye has been put into the bladder. These radiographs will show a “filling defect” in the bladder or a thickened uneven border around the bladder. There is also a test called the Bladder Tumor Antigen Test (BTA) which looks for tumor proteins in the urine. This test, although sensitive, is not highly specific. This means that if the test is negative, there is close to a 100% chance that your pet does not have TCC. However, if the test is positive, it is NOT a reliable indicator that your pet has TCC. The presence of urinary tract infection and blood in the urine can cause false positives. A newer test has been developed that detects a specific mutation of BRAF (CADET BRAF mutation detection assay). This mutation is present in up to 85% of transitional cell carcinomas. A free-catch urine sample can be used. Unlike the BTA, the test is not affected by blood or infection. False positives are not expected, but the false negative rate of sampling can approach 30%. Therefore, a positive test is reliable, but a negative test is not. It is currently being advocated as a screening tool for breeds that are at high risk for the development of bladder tumors. Oftentimes, the only way to definitively diagnose a bladder tumor is to perform a biopsy. A biopsy can be done surgically, endoscopically through the urethra, or sometimes even via a urinary catheter. In the case of TCC, surgery is rarely curative, so attempts to make the diagnosis in less invasive ways are usually attempted first. Urine samples may show abnormal cells, but these can be difficult to interpret, especially if infection or inflammation is present.
Ultrasound of a bladder showing diffuse disease along the bladder wall
Transitional cell carcinoma cells. Multinucleated neoplastic transitional epithelial cell (red arrow). Athens Diagnostic Lab, University of Georgia.
TCC is one of the tumor types that can easily “seed” itself in other locations. For this reason, collecting urine through cystocentesis (a needle into the bladder) should not be done to avoid the risk of seeding the tumor cells in the abdomen or skin in the area. Surgery is usually not possible because of the location that these tumors typically occur. They tend to be found in the “trigone” area of the bladder, which is where the urethra exits the bladder and the ureters (from the kidneys) enter the bladder.
In addition, these tumors often are multifocal within the bladder. In a series of 67 dogs with TCC that underwent surgery, complete tumor-free margins were only obtained in 2 dogs. Of the 2 dogs, one had a relapse in the bladder 8 months later and the other developed metastatic disease.
Are other tests necessary?
Complete staging (determining if any spread of cancer has occurred) is required. Testing includes thoracic radiographs (chest x-rays) to rule out the spread of cancer to the lungs, lymph node aspirate/biopsy if any lymph nodes are noted to be enlarged, CBC, chemistry panel, and free-catch urinalysis to determine general health, and ultrasound of the bladder and entire abdomen (looking for enlarged lymph nodes or any effects the tumor may be having on the ureters and kidneys). A free-catch or catheterized urine sample is preferred over a sample obtained by cystocentesis (a needle placed into the bladder to draw out urine) as seeding of the tumor cells can occur with this needle method.
Treatment of TCC:
Surgery is not generally considered unless the visible tumor is in a location that suggests a tumor type other than TCC. With TCC, the most common form of therapy used is a combination of chemotherapy (Mitoxantrone) and a non-steroidal inflammatory agent (COX-2 inhibitor) called piroxicam (Feldene®). Piroxicam provides strong analgesia and also acts indirectly on the tumor through it’s COX-2 inhibition properties. Piroxicam alone can improve the survival the time of a patients with bladder cancer up to approximately 6 months. When combined with Mitoxantrone chemotherapy, median survival time is generally one year. Many patients can survive much longer. The use of vinblastine chemotherapy or metronomic dosing of chlorambucil have also been described for use in TCC in dogs.
How is treatment administered?
Chemotherapy is administered through an intravenous catheter. Blood work is first performed to be certain that the patient has adequate white blood cells and platelets before administration of chemotherapy. Seven to ten days after treatment a monitoring CBC is required. Treatments are administered at 21 day intervals and typically 5-6 treatments are performed. Length of treatment depends on the response (ultrasound is used to measure tumor response) and how the patient is tolerating the chemotherapy. Piroxicam is an oral medication given at home daily to every other day. If chemotherapy and piroxicam are not effective, radiation therapy can be considered.
In cases where the ureters become obstructed and start to damage the kidneys, special procedures can be utilized to place a “stent” to re-establish the opening of the ureter into the bladder. These procedures are considered palliative and can improve the patient’s quality of life. In a recently published study ( J Am Vet Med Assoc 2006  226-234) dogs with malignant urethral obstructions underwent stenting procedures and in 7 of the 12 dogs evaluated, the outcome was good to excellent.
What supportive care is recommended?
Patients with TCC are at higher risk for urinary tract infections. Sometimes it is difficult to diagnose an infection because one of the indicators of a non-cancer patient with a urinary tract infection can be blood in the urine. In the case of the bladder tumor patient, blood in the urine is not necessarily an indicator of infection. Cystocentesis to obtain a sterile urine sample is contraindicated due to risk of tumor seeding, therefore we often have to rely on a free catch sample. Interpretation of free catch samples can be difficult due to bacterial contamination. However, if patients appear to be straining more or develop an odor to the urine, they should be treated for infection.
Patients may benefit from supplementation of cranberry, which is believed to reduce the incidence of urinary tract infection. In a study in humans (Yale University), cranberry products inhibited the adherence of bacteria to bladder and vaginal epithelial cells. Therefore, there is scientific evidence to support these supplements as a means to decrease infection rates. Specific products and dosages can be discussed with our doctors.