Update on Treatment of Canine Transitional Cell Carcinoma

Update on Treatment of Canine Transitional Cell Carcinoma

Transitional cell carcinomas (TCCs) are the most common tumors of the urinary bladder.  The Scottish Terrier, Sheltie and Beagle are breeds with a higher risk factor for developing this cancer.  Other factors have been associated with a higher risk of development, including female gender, obesity and exposure to chemical lawn pesticides.1 Transitional cell carcinomas are typically very aggressive and invasive tumors associated with a moderate rate of metastasis. The incidence of metastasis to the locoregional lymph nodes in one study was reported to be 39% at initial diagnosis and 58% at necropsy.  Thoracic radiographs have been noted to be positive for pulmonary metastasis in up to 16% of patients at the time of initial diagnosis.2

Because they are often located at the trigonal region of the bladder, complete surgical resection of the tumor is often not possible. There is, however, evidence to suggest that surgical debulking (if a large amount of the tumor can be debulked) followed by adjuvant chemotherapy will extend survival time.2 Intensity-modulated radiation therapy (IMRT) has been investigated in dogs with urogenital tumors in combination with other forms of either local or systemic treatment.  This modality was shown to significantly improve both progression-free intervals and overall survival times.  While it was found to be a well-tolerated form of locoregional therapy, the availability of treatment facilities with both IMRT and image-guided capabilities is limited.3

Chemotherapy in the face of gross disease has also been shown to be effective in treating TCCs.  The combination of traditional cytotoxic chemotherapy with a non-steroidal anti-inflammatory drug results in a 30% overall response rate (with 75% feeling better at home) and a median survival of one year.4

Piroxicam (Feldene) is a non-steroidal anti-inflammatory agent (NSAID) that has been shown to improve clinical signs (hematuria, stranguria, pollakiuria), thus improving quality of life. In some patients, long term use may even result in partial decrease in tumor size.5 Other NSAIDs such as firocoxib and deracoxib have also been shown to be effective in the treatment of transitional cell carcinoma.2,6

There have been several chemotherapeutic agents utilized to treat transitional cell carcinomas.  Prior studies suggest that injectable protocols utilizing mitoxantrone or vinblastine combined with piroxicam may increase both quality and quantity of life.7,8 Other injectable agents, such as doxorubicin, gemcitabine and carboplatin, have been investigated but have not been shown to be of significant benefit.9,10,11,12

Because of the locally aggressive nature of this disease, most dogs are ultimately euthanized due to poor quality of life secondary to significant discomfort or inability to urinate, with up to sixty percent of dogs being euthanized due to urinary obstruction.  Urethral stenting under fluoroscopic guidance has been successfully utilized to manage urethral obstruction in many cases.  As with any treatment modality, patient selection is paramount.  While generally well-tolerated, complications may include urinary incontinence, stent migration and reobstruction.13

Recently, the use of metronomic chlorambucil has been shown to be well-tolerated and able to slow progression of disease for several months after dogs had failed other treatments.14 Newer prospective studies are currently underway to investigate this treatment as both a first-line therapy as well as in combination with traditional cytotoxic agents.  Anecdotal reports of combination vinblastine, piroxicam and metronomic chlorambucil as first-line therapy suggest a promising increase in response rates.  Hopefully, further clinical trials will continue to provide hope for improved outcomes for dogs with transitional cell carcinoma.

Ian Muldowney, DVM  – 2015

The Veterianry Cancer Center

 

References

  1. Knapp D (2013). Tumors of the urinary system. In: Withrow SJ, VailDM, eds. Withrow & MacEwen’s small animal clinical oncology.  5th ed. Philadelphia: WB Saunders Co;572–582.
  2. Knapp D, Glickman N, Widmer W, et al (2000). Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer ChemotherPharmacol,Vol 46:221–226
  3. Nolan M, et al (2012).  Intensity-Modulated and Image-Guided Radiation Therapy for Treatment of Genitourinary Carcinomas in Dogs. JVIM, Volume 26, Issue 4: 987–995.
  4. Fulkerson C, Knapp D (2015).  Management of transitional cell carcinoma of the urinary bladder in dogs: A review.The Veterinary Journal,Volume 205, Issue 2: 217–225.
  5. Knapp D, Richardson R, Chan T, et al (1994). Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med, Vol8:273–278.
  6. McMillan S, et al (2011).  Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder.  JAVMA,Vol. 239, No. 8: Pages 1084-1089.
  7. Henry C, et al (2003).  Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma.  Clinical Cancer Research, Vol 9: 906-911.
  8. Arnold E, et al (2011).  Clinical trial of vinblastine in dogs with transitional cell carcinoma of the urinary bladder. JVIM, Vol 25:1385-1390.
  9. Robat C, et al (2013).  Retrospective evaluation of doxorubicin-piroxicam combination for the treatment of transitional cell carcinoma in dogs.  Journal of Small Animal Practice,Vol 54: 67-74.
  10. Marconato L, et al (2011).  Toxic effects and antitumor response of gemcitabine in combination with piroxicam treatment in dogs with transitional cell carcinoma of the urinary bladder.  JAVMA, Vol 238, No. 8: 1004-1010.
  11. Boria P, et al (2005).  Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder.  Veterinary and Comparative Oncology, Volume 3, Issue 2: 73–80.
  12. Chun R, et al (1997).  Phase II Clinical Trial of Carboplatin in Canine Transitional Cell Carcinoma of the Urinary Bladder.  JVIM,Volume 11, Issue 5: 279–283.
  13. McMillan S, et al (2012).  Outcome of urethral stent placement for management of urethral obstruction secondary to transitional cell carcinoma in dogs: 19 cases (2007-2010).  JAVMA, Vol 241, No 12: 1628-1632.
  14. Schrempp D, et al (2013).  Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma.  JAVMA,Vol. 242, No. 11: 1534-1538.
Posted in