NSAIDs and chemotherapy

The standard-of-care medical therapy for canine transitional cell carcinoma generally combines systemic cytotoxic chemotherapy and the NSAID piroxicam.

Chemotherapy agents that have been studied include doxorubicin, cyclophosphamide, cisplatin, carboplatin, dactinomycin, and mitoxantrone.^33-40 A study in 31 dogs compared three treatment groups: a doxorubicin and cyclophosphamide combination, surgery, and intravesical treatment with the alkylating agent thiotepa. There was a survival advantage for dogs treated with the doxorubicin and cyclophosphamide combination (median survival 259 days) compared with surgery (median survival 86 days) or intravesical thiotepa (median survival 57 days), but the small number of dogs in the study precludes firm conclusions or the routine use of a doxorubicin and cyclophosphamide combination to treat canine transitional cell carcinoma.⁴¹

Mitoxantrone, administered systemically or intravesically, has been extensively evaluated in treating invasive transitional cell carcinoma in people.^43,44 In the veterinary literature, less information on mitoxantrone monotherapy for canine transitional cell carcinoma is available.⁴⁰ Nevertheless, a combination of a platinum agent with either mitoxantrone or doxorubicin, as compared with single-agent platinum therapy, was identified as a positive prognostic variable in one study and led to a median survival time of 358 days.³⁸ Furthermore, a multi-institutional study evaluated the coadministration of mitoxantrone and the NSAID piroxicam in 55 dogs with bladder transitional cell carcinoma. The results were an overall median survival time of 350 days—better than with either agent alone—with the combination being generally well-tolerated.³⁹

General recommendations for systemic therapy

Because of evolving treatment options and recommendations for canine urinary bladder transitional cell carcinoma, consulting a veterinary oncologist is always recommended. When referral is not possible, consider offering palliative therapy with single-agent piroxicam (0.3 mg/kg/day orally with food). Also consider administering a combination of piroxicam and mitoxantrone (5 to 5.5 mg/m² intravenously every 21 days; perform a complete blood count before each administration), currently regarded as standard-of-care therapy by many veterinary oncologists. Both therapeutic options carry high toxicity risks, including kidney (piroxicam), gastrointestinal tract (combination), and bone marrow toxicity (mitoxantrone), so closely monitor patients before and after instituting therapy.

A combination of a chemotherapeutic agent and NSAID other than mitoxantrone and piroxicam cannot be recommended and should be avoided until further studies demonstrate clear advantages with regard to safety and efficacy.

Radiation therapy

In a pilot study in 10 dogs with bladder transitional cell carcinoma that combined external beam radiation therapy with mitoxantrone chemotherapy and piroxicam, nine of the dogs experienced disease stabilization and improvement in clinical signs.⁴⁵ However, the reported survival time of 326 days was comparable to piroxicam and mitoxantrone without radiation therapy. Nevertheless, in dogs with partial or complete obstruction of urinary outflow or dogs experiencing pain associated with the primary tumor or its metastases, radiation therapy is a viable therapeutic option.

Side effects associated with radiation therapy for transitional cell carcinoma are common and can mimic the clinical signs resulting from the tumor. Reported late side effects of radiation therapy, when administered as a single large intraoperative dose to the tumor and surrounding normal tissues, include hydroureter and hydronephrosis secondary to ureteral stenosis.^46,47 Mild to moderate colitis is frequently reported as a late side effect of fractionated radiation therapy to the pelvis, and colonic perforation has been rarely reported.⁴⁸

Given the absence of a clear benefit in terms of disease control or survival times when compared with standard medical management, radiation therapy should be reserved for select cases in which emergency intervention is necessary until additional studies indicate otherwise. Large fractions of megavoltage radiation therapy can help alleviate bone pain from skeletal metastases and are generally well-tolerated with no or minimal side effects.⁴⁹

Palliative and supportive therapies

Figure 6. A 9-year-old male castrated English springer spaniel with bladder transitional cell carcinoma. A cystostomy tube was placed, which improved the dog's quality of life. The dog lived an additional five months. The alopecia on the dogs right flank and thigh is a cosmetic side effect of previous external beam radiation therapy.

Pain management is essential and should focus on the primary tumor, metastatic sites, and hypertrophic osteopathy when present. Intravenous aminobisphosphonate (e.g. pamidronate) administration and palliative radiation therapy are good options for managing metastatic bone pain.^52,53 The main mechanism by which bisphosphonates help alleviate bone pain in skeletal metastasis is by their antiosteoclastic activity.⁵² In our experience, antispasmodic drugs such as the benzodiazepines and phenoxybenzamine may benefit some patients with urethral or prostatic involvement. Renal failure is a potential complication in cases involving advanced local disease resulting in partial obstruction. Intravenous or subcutaneous fluid diuresis is essential to preserve renal function.