An update on diagnosing and treating urinary bladder transitional cell carcinoma in dogs - Veterinary Medicine
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An update on diagnosing and treating urinary bladder transitional cell carcinoma in dogs
These tumors in dogs are difficult to completely resect, so the prognosis for long-term survival is guarded. But new avenues of treatment are being discovered, and treatment protocols already in place can extend and enhance dogs' lives.


VETERINARY MEDICINE


PROGNOSIS

Several prognostic factors have been identified in dogs with transitional cell carcinoma. In a retrospective study of 102 dogs with confirmed transitional cell carcinoma, variables influencing outcome were identified by using the TNM staging system (Table 1).3 Specifically, it was shown that a higher T (primary tumor) stage at diagnosis was associated with an increased risk for developing nodal and distant metastasis, that a younger age was a risk factor for nodal metastasis being present at diagnosis, and that prostatic involvement was a risk factor for distant metastasis being present at diagnosis.3 In that same study, histologic evidence of vascular invasion and urethral involvement were associated with metastasis development after diagnosis.3 A strong correlation between a higher TNM stage at diagnosis and a shorter survival time was observed.

The overall prognosis in dogs with bladder transitional cell carcinoma is guarded. Superficial tumors at the bladder apex can occasionally be removed with margins by cystectomy, potentially leading to long-term survival. Nonetheless, owners should be warned that metastasis can occur and that new bladder lesions may arise after complete excision of a primary tumor. Dogs with nonresectable tumors, comprising most of the canine bladder transitional cell carcinoma patient population, have an unfavorable long-term prognosis, and most dogs will die of their disease, whether from complications from progressive local disease or from regional or distant metastasis. However, treating nonresectable transitional cell carcinoma with chemotherapy and an NSAID, along with palliative and supportive therapy as indicated, can be rewarding and provide a good quality of life for a median of six to 12 months.

FUTURE TREATMENT DIRECTIONS

Future promising therapies target specific dysregulated molecular pathways in transitional cell carcinoma. Research conducted in vitro with human bladder cancer cells revealed dysregulation of the epidermal growth factor signaling pathway.54 Selective inhibition of this pathway with the small molecule tyrosine kinase inhibitor gefitinib (Iressa—AstraZeneca) is a promising therapeutic avenue.54

Photodynamic therapy, which uses light-activated agents with relatively selective accumulation in tumor cells, also shows promise for treating transitional cell carcinoma, especially with superficial lesions. An in vitro study demonstrated the phototoxic effects of 5-aminolevulinic acid-based (ALA) photodynamic therapy on a canine transitional cell carcinoma cell line.55 This method is being evaluated in clinical trials in people, and preliminary results are encouraging.56

In people with high-grade superficial carcinoma in situ (superficial, not invading the basal layer), standard-of-care therapy involves intravesical bacille Calmette-Guérin, an attenuated strain of Mycobacterium bovis, acting as an immunostimulant.57 Intravesical therapy, with either chemotherapeutics or immunotherapeutics, is largely unexplored in veterinary oncology.39,58,59 While this may be due to the typically advanced local stage of disease in canine transitional cell carcinoma, it warrants further investigation.

Perhaps the most important prognostic impact will come in the form of early detection. Current research in people with transitional cell carcinoma focuses on several tumor markers, including the anti-apoptotic protein survivin. Survivin has been detected in 100% of people with new and recurrent bladder cancer and appears to be a reliable and sensitive marker for tumor detection.60 Survivin was recently evaluated as a potential prognostic variable in 15 dogs with transitional cell carcinoma. While the results were not statistically significant, a marked difference was observed in survival times for dogs with tumors expressing survivin (81 days) as compared with dogs with tumors that did not express it (226.5 days).61 Further investigation of this marker is necessary to clarify its utility in the prognosis and early diagnosis of canine transitional cell carcinoma.

CONCLUSION

Despite recent advances in therapeutic intervention, urinary bladder transitional cell carcinoma in dogs remains a frustrating disease for clinicians and owners. While improved quality of life and median survival times approaching one year are now reported, most patients with nonresectable primary tumors will eventually die as a result of inadequate local disease control.

David A. Heller, DVM
Louis-Philippe de Lorimier, DVM, DACVIM (oncology)
Timothy M. Fan, DVM, DACVIM (oncology, internal medicine)
Department of Veterinary Clinical Medicine
College of Veterinary Medicine
University of Illinois
Urbana, IL 61802


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