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Transitional Cell Carcinoma: Once Considered Incurable, Now Highly Treatable

08/02/2010

In many respects, Frankie was a lucky dog. Just a few years ago Frankie’s diagnosis of transitional cell carcinoma (TCC) would have been a death sentence. Dogs with this most common type of urinary bladder cancer had a zero chance of survival. Often they were euthanized as soon as they were diagnosed because there was no known treatment for the disease.

TCC develops from the cells that line the bladder. As the cancer grows, it moves into the bladder wall and muscles. In some cases, the tumor obstructs the flow of urine. In others, the cancer eventually spreads to other organs and the lymph nodes. Either way, the prognosis was bleak. That is, until recently.

Fortunately for Frankie and other dogs, times are changing. Thanks to ongoing research supported by grants from the AKC Canine Health Foundation, the past decade has seen great progress in managing TCC. "It’s definitely a treatable cancer," says Dr. Deborah Knapp, Director, Purdue Comparative Oncology Program, at Purdue University’s School of Veterinary Medicine.

Currently, there are two fairly standard treatments for TCC according to Knapp. One is the use of an intravenous chemotherapy drug, mitoxantrone, along with an oral nonsteroidal anti-inflammatory drug (NSAID), piroxicam. The other is the use of piroxicam alone, particularly in cases where the dog’s owner wants to avoid chemotherapy because of cost or other reasons. (The anti-cancer properties of piroxicam were discovered when it was given to dogs with other types of cancer to control their pain, and the cancer went into remission in some cases.) Other chemotherapy drugs, such as carboplatin and cisplatin have also been used successfully in combination with piroxicam. However, they tend to cause more side effects so are used less often.

In Knapp’s clinical trials, dogs often try several different drugs. When one drug is no longer effective, another drug is given. With several different treatments now available, Knapp says "there is approximately a 75% chance that we can control or cause regression of the cancer." In other words, the cancer remains stable or shrinks.

Frankie was one of the dogs who benefited from the clinical trials at Purdue. In 2007, Laurie Hoffman of Schererville, Ind. noticed her nine-year-old Scottish terrier, Frankie, was experiencing frequent and strained urination. While this, along with blood in the urine, can be a symptom of several common problems such as bladder stones, bladder inflammation, or a bladder infection, it also can be a sign of TCC. Says Hoffman, "We immediately had a red flag go off in our heads, because we knew Scottish terriers have a high incidence of bladder cancer." An ultrasound indicated a large mass in Frankie’s bladder, and a biopsy confirmed the diagnosis of TCC.

During the biopsy at Purdue, a substantial portion of the tumor was removed. As with most cases of TCC, however, the location of the tumor made complete excision impossible. Hoffman’s next step was to enroll Frankie in a clinical trial at Purdue where Frankie received mitomycin C, an investigational drug, administered directly into his bladder through a catheter. The drug stayed in the bladder for an hour and was then removed through the catheter.

This intravesical method delivered a concentrated amount of the mitomycin C directly to the tumor and also reduced the risk of side effects such as those that often accompany intravenous chemotherapy. Indeed, Frankie had absolutely no side effects according to Hoffman. "He would sleep in the car on our [hour and a half] ride home and would then be hungry for a big meal!!!"

That’s not to say this treatment has no risks. While Frankie and many other dogs in the research study did well on the intravesical therapy, with roughly half the dogs having remission of their cancer and few side effects, a couple of dogs weren’t so lucky. In those cases the drug didn’t remain in the bladder. Instead, it traveled throughout the dogs’ bodies causing side effects similar to the severe toxic reactions that can result from intravenous chemotherapy. According to Knapp, researchers don’t know which dogs will be affected this way. Consequently, intravesical mitomycin C therapy remains under study, but may be used in dogs who don’t respond to standard treatments.

Frankie participated in the Purdue study for 10 months. During that time, he had good quality of life. According to Hoffman, "Frankie was doing absolutely great; the tumor was not growing, everything was stable, and he felt perfect." Then things began to change. Frankie developed intermittent pain in his foot. X-rays revealed nothing, but the problem got worse until Frankie reached a point where he couldn’t move his back legs. An MRI found the cancer had spread to Frankie’s spine. At that point, Hoffman made the decision to let her beloved Scottie go.

Ten months might not seem like a long time, but compared to a survival rate of zero days, it’s easy to see why Hoffman was "very glad we participated and would definitely do it again." Knapp’s research has led to significant strides in treating TCC.

And drug therapy isn’t the only area seeing progress. With support from the AKC Canine Health Foundation, Knapp and the Purdue researchers have been studying both genetic and environmental factors to determine their roles in TCC. Both are important.

Researchers suspect there are genetic factors at work in TCC because certain breeds, such as Scottish terriers, West Highland white terriers, Shetland sheepdogs, beagles and wire hair fox terriers are much more likely than others to develop the disease. Knapp says they are making progress in this area and "are much closer to finding the actual gene" associated with TCC. With this information, they expect to develop strategies for detecting the disease earlier when it may be more responsive to treatment.

Environmental factors play a role, too. According to Knapp, dogs at greatest risk of developing TCC are those that are both genetically predisposed to the cancer and exposed to harmful environmental factors such as lawn chemicals and insecticides. At the other end of the spectrum, studies have identified helpful environmental factors, too. One such study of Scottish terriers showed dogs who ate vegetables at least three times a week had a 70% decrease in the risk of developing TCC.

Knapp sums up the progress very well: "We have reached a point where we consider TCC very treatable and where we expect most dogs to have several months to over a year of very good life. We expect a small percentage to live multiple years, and a few lucky dogs to be cured." And the future looks even brighter. With the potential discoveries in Purdue’s current research on TCC, we can expect to see even more improvements in diagnosis and treatment.

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