By Daniela Ackley, DVM, DACVIM
MSPCA-Angell West, Waltham
Urinary bladder cancer in dogs is a challenging disease to diagnose, stage, and treat. Invasive transitional cell carcinoma (TCC) is the most common form of canine urinary bladder cancer affecting tens of thousands of dogs worldwide each year, and the prevalence appears to be on the rise. Most TCCs are intermediate to high-grade papillary infiltrative tumors; superficial, low-grade tumors are uncommon. TCC is most often located in the trigonal region of the bladder. In one large study of 102 dogs with bladder TCC, more than half of the patients had concurrent urethral involvement and about a third of male dogs had concurrent prostatic disease.1 Distant metastases are typically present in about 20% of cases at diagnosis, and are associated with a worse prognosis. More than 50% of dogs with TCC have distant metastases by the time of death2. Apart from regional lymph nodes and lungs, the metastatic spread can be seen in liver, spleen, kidneys, bones, adrenal glands, heart, brain, and skin.
The mean age at diagnosis is 9 to 11 years, with females being affected more commonly. A strong breed association has been reported with a 21-fold increased risk in Scottish Terriers, and a 3-6-fold increased risk in Eskimo dogs, Shetland Sheepdogs, West Highland White Terriers, Keeshonds, Samoyeds, and Beagles compared to mixed breed dogs.2 In dogs with high breed-associated risk, the sex predisposition is less pronounced. Environmental risk factors for developing TCC include exposure to older-generation flea control products, herbicides, and pesticides.3 Scottish Terriers that consumed vegetables at least three times a week had a 70% reduction in risk of developing TCC.4
The most common clinical signs include hematuria, dysuria, and pollakiuria. Dogs with the advanced disease resulting in ureteral obstruction and hydronephrosis may show signs of abdominal pain and have a palpable, enlarged kidney.
Diagnosis of a TCC is frequently delayed given the non-specific lower urinary tract signs. Many patients are treated with repeated antibiotic trials. While an antibiotic course may provide temporary relief of symptoms, the underlying tumor is progressing. Urinary tract infections (UTI) are common with 55% of dogs having at least one positive culture concurrently.5
Persistent or recurrent urinary signs despite appropriate antibiotic therapy warrant further investigation. In middle age to older dogs of breeds with high risk of TCC, it is appropriate to evaluate for TCC on initial presentation. Furthermore, blind cystocentesis is associated with risks of seeding the malignancy along the needle tract. The delay in correct diagnosis increases the possibility of metastatic disease by the time of detection, worsening the prognosis.
Abdominal ultrasound is commonly used to evaluate the bladder wall, kidneys and ureters, as well as for possible metastatic spread within the abdominal cavity. A recent study showed that some ultrasonographic characteristics including bladder wall invasion, echo pattern, and location can be used as prognostic indicators.6 In this study, dogs with ultrasonographic wall involvement (vs. noninvolvement), heterogeneous mass (vs. homogeneous mass), and trigone location (vs. other locations) had significantly shorter survival times. Ultrasound reliably predicted bladder wall involvement as confirmed by histopathology (Fig. 1). Definitive diagnosis requires cystoscopy or surgical biopsy of abnormal tissues with histopathology.
Fig. 1. Ultrasonographic images (upper panels) and corresponding histopathology slides (lower panels).
Picture A shows bladder mass invading the muscular layer (asterisk) as evidenced by histopathology (M smooth muscle, T tumor cells). There is no evidence of ultrasonographic or histopathologic invasion of deeper bladder layers in Pictures B (tumor) or Picture C (P polypoid cystitis). Hanazono KM, VRUS 2014;55(1):79-84.
New detection assay for TCC
Three recent articles published by researchers at North Carolina State University (NCSU) and the National Institutes of Health (NIH) describe detection of a new mutation in canine TCC tissue samples.7,8,9
These two independent groups of researchers discovered the same mutation in the same gene (BRAF gene), using two different approaches. Mutations of the BRAF gene are also found in human cancers and result in a mutated protein with increased kinase activity. This change leads to abnormal proliferation and tumor growth. Evaluation of hundreds of canine histopathologic TCC samples detected the BRAF mutation in 85% of them. These studies showed that the mutation was not present in non-neoplastic inflammatory bladder tissues, polyps, or in various other cancers. Researchers were able to develop a rapid and sensitive test to detect this mutation in cells shed into the urine called CADETSM BRAF Mutation Detection Assay. The data show that a positive result is >99% specific to TCC. That means that you can truly trust a positive result. However, the sensitivity is around 75-85%, so negative results do not rule out the possibility of dogs having BRAF-negative TCC.Another major advantage is that the assay is not affected by hematuria or bacteriuria. The test is also quantitative: the level of mutation generally correlates with the extent of disease. Higher levels of BRAF mutated cells are detected in dogs with advanced disease (visible mass on AUS). The test also detects dogs with emerging TCC not visualized yet by conventional methods such as AUS or cystoscopy. This test may be used in the future for monitoring of the response to therapy.
When a CADETSM BRAF Mutation test is negative, it could mean one of three possibilities: 1) The patient does not have a TCC, but instead has a benign polyp or inflammation; 2) the level of mutation is below the threshold of detection due to low number of cells shed into the urine, or 3) the patient is one of the 15% of dogs that has a TCC not associated with a BRAF mutation.
The laboratory requires 40mL of urine to be submitted, which can be challenging to collect in small dogs. This requirement applies to dogs that areasymptomaticand may have an early disease. Larger urine volume increases the chances of recovering sufficient cell numbers to detect BRAF mutation. However, if a dog is already diagnosed with a mass accompanied by urinary tract signs, 10-20ml is usually enough.
The company provides a preservative that stabilizes the urine once mixed, so urine can be collected from an individual dog on repeated occasions over a day or two to get the volume needed in the collection jar.The urine needs to be collected into a clean container and then immediately transferred to the collection jar, swirled to mix with the preservative and set aside at room temperature (out of direct sunlight) until it is sent to the laboratory.
Unfortunately, this test did not prove useful in cats. Only small numbers of cats were tested due to a low prevalence of TCC in cats; however, a BRAF mutation was not identified in feline TCC samples.
Given the high sensitivity of this test and ability to detect very early disease, screening of middle-aged dogs from high-risk breeds can be considered. This approach was already put in practice, revealing the presence of the BRAF mutation more than 4 months before the onset of clinical signs. This provides exciting new opportunities for medical or surgical treatments, as complete surgical removal is not possible at later stages. Development of this new test holds promise to change our way of diagnosing and treating this insidious cancer in dogs.
- Knapp DW et al. Naturally-occurring canine transitional cell carcinoma of the urinary bladder: a relevant model of human invasive bladder cancer. Urol Oncol 2000;5:47-59.
- Knapp DW et al. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development. ILAR Journal 2014;55:100-118.
- Glickman LT et al. Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers. JAVMA 2004;224(8):1290-1297.
- Raghavan M et al. JAVMA 2004;225:389.
- Budreckis DM et al. Bacterial urinary tract infections associated with transitional cell carcinoma in dogs. JVIM 2015;29(3):828-833.
- Hanazono KM et al. Ultrasonographic findings related to prognosis in canine transitional cell carcinoma. VRUS 2014;55(1):79-84.
- Mochizuki H at al. Detection of BRAF mutation in urine DNA as a molecular diagnostic for canine urothelial and prostatic carcinoma. Plos One 2015:Dec:1-12.
- Mochizuki H at al. BRAF mutations in canine cancers. Plos One 2015:June:1-9.
- Decker B at al. Homologous mutation to human BRAF V600E is common in naturally occurring canine bladder cancer – evidence for a relevant model system and urine-based diagnostic test. Mol Cancer Res 2015:13(6):993-1002.
Some tests your veterinarian may recommend if a bladder tumor is suspected include urinalysis (microscopic examination of a urine sample), ultrasound of the abdomen, biopsy to confirm the diagnosis if a mass is found within the bladder, and radiographs of the chest to check for potential spread of the tumor to the lung ...How do you diagnose transitional cell carcinoma? ›
- ureteroscopy to check for abnormalities in each ureter and renal pelvis.
- intravenous pyelogram (IVP) to evaluate the flow of fluid from the kidneys to the bladder.
- CT scan of the kidneys and bladder.
- ultrasound of the abdomen.
- biopsy of cells from each renal pelvis or ureter.
The specificity of this test is >99.5%. All cases that have the presence of this mutation have had histopathologic confirmation of urothelial carcinoma. Normal dogs, dogs with benign polyps or inflammation of the urinary tract will not harbour the BRAF mutation.How long can a dog live with transitional cell carcinoma? ›
Dogs with no involvement of local lymph nodes had a 234 day survival time compared to 70 days for dogs with local lymph node involvement. Dogs with evidence of distant tumor spread had a median survival time of 105 days while those without distant spread had a survival time of 203 days.How much does a BRAF test cost? ›
From the perspective of a commercial payer, the average cost of sequential testing was estimated at 3,299 ($406 for BRAF, $1,127 for ROS1, $1,070 for ALK, and $696 for EGFR), that of exclusionary mutation testing was estimated at $3,763 ($406 for BRAF, $1,127 for ROS1, $1,070 for ALK, $696 for EGFR, and $464 for KRAS), ...How long can a dog live on piroxicam? ›
The median survival in dogs treated with early chemotherapy alone (cisplatin or carboplatin) at Purdue University was 130 days. Median survival with piroxicam treatment in 76 dogs with TCC was 244 days. The median survival of dogs receiving vinblastine and piroxicam was 299 days.Where does TCC spread to first? ›
Main Points. Transitional cell carcinoma (TCC) of the bladder commonly metastasizes to the pelvic lymph nodes, lungs, liver, bones, adrenals, or brain. Unusual sites include the heart, kidney, spleen, pancreas, and reproductive system.What is the prognosis for transitional cell carcinoma? ›
The prognosis for any patient with metastatic or recurrent transitional cell cancer is poor. The proper management of recurrence depends on the sites of recurrence, extent of prior therapy, and individual patient considerations.What is the survival rate of transitional cell carcinoma? ›
With regard to the tumor grade, the 5-year cancer-specific survival rates are reported to range from 90% to 100% for low-grade UUT-TCC and from 28% to 46% for high-grade UUT-TCC [20,21].Can TCC in dogs be cured? ›
TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it.
The limiting factor on the test so far for us in the clinic is roughly 10 days to 2 weeks turnaround time, however, the test is excellent for several purposes: Diagnosing TCC in dogs with moderate urinary clinical signs, where signs can be controlled with an NSAID whilst waiting for the results.What is the cadet BRAF test for dogs? ›
CADET® BRAF is a DNA-based diagnostic test that detects the presence of a single mutation present in 85% of confirmed cases of canine transitional cell carcinoma (TCC), also called urothelial carcinoma (UC).Are dogs with TCC in pain? ›
Dogs with the advanced disease resulting in ureteral obstruction and hydronephrosis may show signs of abdominal pain and have a palpable, enlarged kidney. Diagnosis of a TCC is frequently delayed given the non-specific lower urinary tract signs. Many patients are treated with repeated antibiotic trials.Does piroxicam shrink tumors in dogs? ›
Because of its ability to reduce the COX-2 enzyme, piroxicam is used in the treatment of many types of tumors, including nasal epithelial tumors, mammary tumors, colorectal tumors, oral squamous cell carcinoma, oral melanoma, prostatic carcinoma, transitional cell carcinoma (TCC) of the urinary bladder, and ...Is transitional cell carcinoma fatal? ›
Overall survival and cancer-specific survival
For the entire cohort, there were 986 (51.6%) patients who died and 704 (36.9%) patients who died from primary transitional cell carcinoma of the ureter. The median overall survival (OS) was 46 months, and the 5-year OS rate was 41.8%.
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 strongly suspected because TCC is more common in specific breeds of dogs.What is a urine BRAF test? ›
CADET® BRAF evaluates urine samples from dogs for the presence of cells containing a mutation for canine bladder/prostate cancer (TCC/UC). It's cutting-edge technology that is accurate, affordable, and convenient for both veterinarian and pet owner.How long does it take to get BRAF results? ›
With some cancers, rapid tests for BRAF may be done, and you may receive your results within a week. Unlike rapid tests for BRAF, however, DNA sequencing tests (next-generation sequencing) can sometimes take two weeks to four weeks before results are available.What are the side effects of piroxicam in dogs? ›
Piroxicam can cause significant gastrointestinal ulceration and bleeding, as well as kidney damage. Other possible side effects include central nervous system effects such as dizziness, ringing in the ears, itchiness and rash, and limb swelling. Your veterinarian may notice elevated liver enzymes with bloodwork.How much piroxicam can a dog take? ›
Dosing Information of Piroxicam for Dogs and Cats
For an anti-inflammatory effect, piroxicam is dosed at 0.15 mg per pound (0.3 mg/kg) every 24 to 48 hours. To treat transitional cell carcinoma, piroxicam is dosed at 0.15 mg per pound (0.3 mg/kg) once daily.
The acute toxicity signs of piroxicam at doses 207.5 mg/kg and above observed in the animals are torticollis, opisthotonos, somnolence, lethargy, diarrhea, gastroenteritis, generalized internal bleeding, anemia, congestion of the lung and liver, flaccid paralysis, cheesy lung, urinary incontinence, engorged urinary ...What is a high grade TCC? ›
High-grade TCC is the type of bladder cancer that is more likely to be life-threatening. Because transitional cells line many different parts of your urinary tract system, you can sometimes develop tumors in more than one place.What is the primary symptom of transitional cell carcinoma? ›
Symptoms. The symptoms of transitional cell cancer of the kidney are similar to those of other types of kidney cancer. They include blood in the urine and pain in your back, between the lower ribs, and the top of your hip bone. You may also need to pass urine very often or have pain when passing urine.How aggressive is transitional cell carcinoma? ›
Transitional Cell Carcinoma: An Aggressive Cancer
This cancer may spread rapidly, affecting other organs and becoming life-threatening in some cases. Because of this, it's especially important to know more about this disease and its symptoms, as well as your treatment options at Regional Cancer Care Associates.
Most transitional cell cancer of the renal pelvis and ureter can be cured if found early.How common is transitional cell carcinoma? ›
|Transitional cell carcinoma|
|Other names||Urothelial carcinoma|
- Blood in the urine.
- A pain in the back that doesn't go away.
- Extreme tiredness.
- Weight loss with no known reason.
- Painful or frequent urination.
Risk of bladder cancer
Overall, the chance men will develop this cancer during their life is about 1 in 27. For women, the chance is about 1 in 89.
How long will my dog live with bladder cancer? Sadly, when it comes to bladder cancer in dogs the prognosis isn't good. Typically, dogs diagnosed with bladder cancer will live for about 4-6 months without receiving treatment and 6-12 months with treatment.How effective is gabapentin for dogs? ›
There are conflicting clinical reports about its efficacy when used for this purpose, although some studies report improvement in as many as 50% of dogs studied. In dogs, oral Gabapentin is well absorbed in the duodenum, with peak levels occurring approximately one to two hours after administration.
What is a BRAF mutation? A BRAF mutation is a spontaneous change in the BRAF gene that makes it work incorrectly. A mutation causes the gene to turn on the protein and keep it on, which means certain cells get ongoing signals to keep dividing and no instructions on when to stop. This can lead to development of a tumor.Does BRAF test need to be refrigerated? ›
A free catch urine sample of 40mls must be placed in the provided collection cup (available from Antech) and does not require refrigeration. A positive result is 100% diagnostic for urogenital cancer (TCC of bladder, urethra, or prostate).What is transitional cell carcinoma? ›
(tran-ZIH-shuh-nul sel KAN-ser) Cancer that begins in cells called urothelial cells that line the urethra, bladder, ureters, renal pelvis, and some other organs. Urothelial cells are also called transitional cells. These cells can change shape and stretch without breaking apart. Also called urothelial cancer.Can bladder tumors in dogs be benign? ›
Bladder tumors are usually malaignant with only 3% of tumors being benign. Malignant tumors: transitional cell carcinoma is most commonly diagnosed, however other reported tumor types include squamous cell carcinoma, adenocarcinoma, fibrosarcoma, leiomyosarcoma and hemangiosarcoma, botryoid rhabdomyosarcoma.How quickly does piroxicam work? ›
This medicine usually begins to work within 1 week, but in severe cases up to two weeks or even longer may pass before you begin to feel better. Also, several weeks may pass before you feel the full effects of this medicine.Does prednisone help shrink tumors in dogs? ›
We therefore conclude that prednisone is effective in some canine mast cell tumors. Further studies are indicated to determine the most effective dose of prednisone, the appropriate duration of treatment, and the efficacy in more benign mast cell tumors, and in combination with other forms of therapy.Will prednisone shrink a tumor? ›
For some cancers (such as lymphoma, leukaemia, mast cell tumours and multiple myeloma), immunosuppressive dosages of prednisolone can potentially kill cancer cells (i.e. shrink the tumour).Can TCC in dogs be cured? ›
TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it.How long does it take to get BRAF results for dogs? ›
The limiting factor on the test so far for us in the clinic is roughly 10 days to 2 weeks turnaround time, however, the test is excellent for several purposes: Diagnosing TCC in dogs with moderate urinary clinical signs, where signs can be controlled with an NSAID whilst waiting for the results.