What are Bladder Tumors in Pets?

BLADDER CANCER

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.

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 [229]; 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.