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Afterlife
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:

  • Hematuria - Brown color or blood in the urine
  • Pollakiuria -  Frequent urinations, usually in small amounts
  • Dysuria - Difficult or painful urination
  • Poor response to antibiotics for a suspected urinary tract infection
Diagnosis
Treatment
Treatment options include:
  •        Surgical Excision
  •        Chemotherapy
  •        Non-steroidal anti-inflammatory drugs

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:

  • Complete medical history and thorough physical examination including rectal examination to evaluate the urethra, bladder neck, prostate gland in males and local lymph
    nodes.

  • Abdominal and chest X-rays to evaluate for abnormalities of the bladder, enlargement of local lymph nodes and spread of cancer to the lungs. It is not unusual for
    bladder cancer to spread to the local lymph nodes in the abdomen.

  • Serum biochemistry tests to evaluate your pet's general health, assess the function of other organs such as the liver and kidneys and identify electrolyte and acid base
    disturbances.

  • Urinalysis to evaluate for the presence of white cells, red cells, bacteria and crystals. Occasionally, bladder tumor cells can be identified by microscopic examination of
    the urine. Kidney function can be evaluated by a test of urine concentration called “specific gravity.”

  • Abdominal ultrasound to evaluate for tumors in the bladder and urethra, stones in the urinary tract, or urinary tract obstruction. Ultrasound examination allows internal
    structures to be evaluated on a monitor as ultrasonic waves are transmitted to and reflected from tissues.

  • Special contrast X-ray studies to evaluate for bladder tumors, stones, or urinary tract obstruction. Radiographic dye is called “positive” contrast because it appears white
    on the X-ray, and air is called “negative” contrast because it appears black on the X-ray. Either can be introduced into the bladder via the urethra to evaluate for bladder
    tumors. Such a study is called a urethrocystogram.

  • Cystoscopy to evaluate the urethra and bladder for stones, tumors or congenital defects. Cystoscopy is a specialized test in which a flexible or rigid scope is passed into
    the urethra and bladder for direct visualization while the pet is under general anesthesia.  It allows bladder tumors to be identified by their characteristic “frond-like”
    appearance and allows biopsy samples to be taken for pathologic analysis and staging.

  • The V-TBA, or urinary tumor bladder antigen, test has recently been developed which allows for identification of tumor markers in urine.   This new tumor antigen test
    may help diagnose TCC in its early stages as a screening test. Unfortunately hematuria causes false positives and since hematuria is the chief symptom in TCC, the test
    is limited.  
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