The Dog Cancer Survival Guide (106 page)

When you need to look up the definition of a word or phrase, find it listed in
Chapter 5
, which begins on
page 46
.

The ureters, the bladder and the urethra are lined with special cells called transitional epithelial cells, unusual cells that can change shape – stretch or contract – and make it possible for these organs to accommodate the fluctuations in the amount of urine present in the system. Transitional cell carcinoma develops in, and is named for, these cells.

TCC most commonly develops in the trigone, the triangular area formed by the two ureters and the urethra on the inside of the bladder wall. In over half of TCC cases, tumors extend from the bladder down into the urethra. Thirty percent of male dogs with TCC also have it in their prostates, arising from where the urethra passes through the prostate.

TCC is the most common bladder and urethra cancer (squamous cell carcinoma, lieomyosarcoma, and lymphoma follow). While cancer of the lower urinary tract is relatively rare in dogs, the majority of cancers are malignant and metastatic. Bladder TCC in particular is both locally invasive and highly metastatic, spreading most commonly to the lymph nodes, lungs, liver and bone.

There are several environmental factors that can contribute to the development of TCC, but there also seems to be a genetic risk for some breeds. At high risk are Shetland Sheepdogs, Beagles, Collies, and many terriers (Scottish, West Highland White, Airedale, and Wirehaired Fox). The two breeds at highest risk are Scottish Terriers and Shetland Sheepdogs.

TCC development is associated with exposure to insecticides, including household insecticides, the mosquito-killing compounds often sprayed on marshland, and topical flea and tick medications. For this reason, I recommend the new spot-on topical flea control products, which appear to be safer, especially for high-risk breeds. Exposure to herbicides, such as weed-control chemicals and other lawn chemicals, is also a risk factor.

Female dogs have a greater tendency to develop TCC than male dogs do, perhaps because male dogs urinate more frequently, as they mark their territory. As their urine spends less time in the bladder, the toxins from pesticides and herbicides and other carcinogens spend less time in contact with the urinary tract.

Obese dogs are at a higher risk for TCC, for a similar reason – cancer-causing toxins are often stored in fat cells, which contribute to the developing cancer.

Dogs treated with the chemotherapy drug cyclophosphamide are also at a higher risk for developing TCC, due to urinary tract damage.

A study has shown that Scotties, consuming vegetables at least three times a week, had a decreased risk of bladder cancer. The addition of vegetables to your dog’s diet (such as those in Dr. Dressler’s cancer diet) may be helpful.

Transitional cell carcinoma can be misdiagnosed as a urinary tract infection because the symptoms are so similar. The signs for each condition are identical: straining to urinate, blood in the urine, and frequent, small urinations. Some dogs may also strain when defecating. To complicate matters further, many dogs with TCC have a secondary bladder infection, too. If underlying cancer is not suspected, antibiotics may help to alleviate the symptoms, for a time. When symptoms recur, especially in older dogs, vets should check for TCC.

Urinary tract infections are irritating and painful because there is the constant urge to urinate, even when the bladder is not full. The location of the tumor can also result in partial or complete obstruction of the flow of urine. For example, the trigone region, where TCC most often develops, is very sensitive to pressure – when it’s stretched we feel the urge to urinate – and a tumor here can be uncomfortable.

Urinary tract tumors can also be dangerous, because they can significantly alter the functioning of the whole system. If you think of the urinary system as a hose, and imagine putting a kink in that hose, you’ll understand how this works: kinks “back up” the water and lead to a stretching above the obstruction. A partial obstruction of the urinary tract can cause a dilation (widening) of the ureters and fluid to back up into the kidneys, which can lead to kidney failure. A complete obstruction can quickly become a life-threatening emergency.

Sometimes dogs are diagnosed after they are brought in to the vet for lameness or difficulty walking. In these cases, X-ray examinations usually reveal bone lesions, which turn out to be metastatic TCC.

There is a screening test for TCC, called the Veterinary Bladder Tumor Antigen test (VBTA test). The test can be run at your vet’s office, and requires a free-catch urine sample, which you can collect yourself, no more than 48 hours old. If this test is negative, it is very unlikely that the dog has TCC, and further work-up is likely to be unnecessary. If the VBTA test is positive, however, TCC is suspected and further tests should be run to confirm the diagnosis. Positive results are not confirmation for TCC, because false-positives can occur if there is blood and protein in the urine, which happens during bladder infections. Because of this, the usefulness of the VBTA is limited when the dog is already sick; it is best used as an early screening test for normal, asymptomatic dogs at high risk for developing TCC.

If TCC is suspected, with or without VBTA tests, urinalysis is usually the first test. This can be a free catch sample or a sterile sample collected directly from the bladder. The urinalysis usually shows elevated white blood cell levels, elevated red blood cell levels, and proteins and bacteria in the urine. These results, unfortunately, are what would also be expected in the case of a urinary tract infection. Although the examination of the urine sediment reveals tumor cells in about one-third of cases – even this discovery does not confirm TCC, because normal transitional cells can appear unusual and cancerous if there is a lot of inflammation in the system (which there is, during an infection).

To get a sterile urine sample to confirm a bladder infection, a cystocentesis is performed. A needle is inserted through the abdomen, directly into the bladder, so that a urine sample can be drawn into a collecting syringe. This is often done with ultrasound guidance, and does not usually require sedation. Then this urine sample must be cultured at the lab to determine whether there is a urinary tract infection, and what are the appropriate antibiotics to treat it.

Cystocentesis has its risks for patients with TCC; there have been reports of tumor cells seeding the track of the needle as it is withdrawn from the body, effectively spreading the cancer. Also, seeding tumor cells can occur while handling the tumor during regular bladder surgery, so caution is recommended in general. Proper oncology surgery guidelines dictate that the surgeon change gloves and instruments after handling all tumors and before suturing the patient closed. While cystocentesis has its risks, it is debatable whether to avoid the procedure in all patients. Secondary UTIs are common at diagnosis and during treatment, and many of my patients recently had a cystocentesis as part of their bladder work-up. So, if your dog had a cystocentesis just before the diagnosis, don’t worry. Getting a urinary tract infection diagnosed and properly treated is just as important.

Since the cytology of urine found during a routine urinalysis only confirms TCC in a third of cases, a biopsy is often required to confirm a diagnosis and initiate a treatment plan. The best biopsy samples come from cystoscopy (using a fiber-optic scope passed through the urethra into the bladder) or from a bladder surgery (both of these require general anesthesia), although an ultrasound may also show the tumor.

The tumor’s size and location is important to know and a little tricky to discover, because the bladder’s function as a constantly changing hollow organ means it looks different depending upon how much urine is inside. The ideal way to make sure that the size and location are fully understood is for the vet to pass sterile saline fluid through a catheter into the bladder to fill it. The bladder is first emptied of urine and then filled with the same amount of fluid volume every time an ultrasound is performed; this is the only way to be sure that measurements are consistent, from one test to the next. Since female dogs need to be sedated for catheterization, do discuss the pros and cons of this procedure with your vet.

Abdominal ultrasounds can also help look for metastasis within the abdomen. The liver is a common location for metastasis, as are the regional lymph nodes; fifteen percent of TCC infections have spread by the time of diagnosis. Looking for metastasis is important, because half of all dogs will experience spread as the disease advances. In addition to ultrasound, three-view chest X-rays or chest CT scans should be done to check the lungs for spread. I recommend that these images be reviewed by a board-certified radiologist, as chest X-rays are commonly misinterpreted in older dogs. For example, lung nodules may represent benign, age-related changes but appear cancerous to an untrained eye. If a qualified radiologist is not available, I recommend suspending judgment on lung nodules and checking them later for changes. If they change, they may indicate spread – if they stay the same, they may just be age-related. A chest CT scan is more sensitive and may show more details than an X-ray.

In addition to these imaging tests, I recommend running routine blood work to check the general health of your dog. If increased kidney markers or high potassium levels are found, this can indicate an obstruction of the urinary tract by the tumor, and emergency measures must be taken to unblock it. If a catheter cannot be used, stents placed surgically might be needed to allow the urine to flow while treatment is begun.

The best way to determine the long-term prognosis is to look at the stage of TCC at the time of diagnosis.

• Stage T1:
  Superficial tumor.
  
• Stage T2:
  The tumor is in the wall of the bladder.
  
• Stage T3:
  The tumor is invading the surrounding tissue or organs.
  

T1 tumors generally respond better to treatment, and dogs with no metastasis have a median survival time of six to seven months.

Dogs with lymph node metastasis or metastasis to distant locations (liver, lungs or bones, for example) have a median survival time of two to three months.

If the prostate gland is involved, the prognosis worsens. The prognosis also worsens if the dog is young.

If left untreated, TCC can cause significant pain and loss of quality of life; a urinary system obstruction is also possible. We do not have any statistics to tell us the median survival time for dogs left untreated; my guess would be that these factors would limit life to a couple of months. The irritation and pain of this illness is hard for your dog and his owner to bear.

There are three goals for treating TCC: to make the dog more comfortable, to control the primary mass, and to prevent or delay metastasis.

Surgery is usually the first treatment used, although not curative for bladder TCC because it is usually impossible to completely remove (excise) a bladder tumor that is not caught very early. The trigone, where most bladder tumors develop, is a complex area of urinary tubes and nerves, making it very difficult to perform an aggressive surgery and achieve clean margins. It can be hard for any surgeon to determine which tissue is normal and which is not, by sight alone. Many dogs also have microscopic multifocal lesions; these microscopic cancerous or precancerous cells can occur even in normal bladder tissue. For this reason TCC recurrence is very common, even when a biopsy indicates clean margins.

Why do surgery, if it doesn’t help to cure TCC? Because surgery can debulk (reduce the size of) tumors that may otherwise cause an obstruction, and it can decrease the tumor burden in the bladder, giving your dog less pain and more time. Surgery also has the potential to make chemotherapy more effective.

Dogs treated with surgery alone live only three to four months, because TCC tends to recur and is highly metastatic. Adding post-surgical chemotherapy treatments can prevent recurrence, prevent or delay metastasis, and extend survival times.

The most common protocols use mitoxantrone combined with the NSAID piroxicam, which extends survival times to twelve to fourteen months. About twenty percent of afflicted dogs respond to protocols that use piroxicam alone; these dogs experience a six to seven month median survival time and an overall good quality of life. Piroxicam is an NSAID, so it can cause stomach ulceration when used over the long-term, which is why I recommend giving misoprostol throughout treatments to protect the stomach.

While mitoxantrone and piroxicam protocols are considered the standard of care, there are other chemotherapy protocols, which use doxorubicin and platinum-based drugs, such as carboplatin and cisplatin. Carboplatin is safer for the kidneys than cisplatin, and dogs respond better when it is combined with piroxicam. The opposite is true for cisplatin – all NSAIDs, including piroxicam, worsen kidney toxicity when they are used with cisplatin, so, be careful not to give anti-inflammatories when your dog is on cisplatin (the use of any platinum-based drug requires careful monitoring). These protocols are likely to evolve as other chemotherapy drugs (such as vinblastine) are evaluated.