Bladder Matters - Treatment Options for Transitional Cell Carcinoma
World Small Animal Veterinary Association World Congress Proceedings, 2013
Anthony J. Mutsaers, DVM, PhD, DACVIM (Oncology)
Ontario Veterinary College, University of Guelph, Guelph, ON, Canada

While bladder cancer is not common in the dog, transitional cell carcinoma (TCC) is by far the most common form of this disease, and clinicians are detecting cases at earlier stages than in the past. Risk factors for development of TCC include female gender, obesity, topical insecticide exposure, and certainly breed. In North America many terrier breeds are overrepresented including Scottish, West Highland White, and Wire Haired Fox. Beagles and Shetland sheepdogs also appear to be predisposed. Stranguria, hematuria and pollakiuria are common clinical signs. Transient or lack of response to appropriate antibiotic therapy for treatment of chronic urinary tract infections is also a frequent historical finding. Cystocentesis may result in seeding tumour cells, so urine is generally collected by catheterization (may be difficult with the presence of an obstructive mass) or free catch when TCC is suspected. Urinalysis may reveal neoplastic cells in the sediment of approximately 30% of dogs with TCC. Bladder tumour antigen tests have been evaluated in dogs, with low specificity for TCC in the presence of other urologic diseases. However, the sensitivity was considered acceptable, and therefore potential screening capabilities exist for highly TCC-susceptible breeds.

Staging and Treatment

The most common location within the bladder for TCC is the trigone, which presents difficulty for complete surgical removal, and predisposes to neoplastic obstruction of the urethra and/or ureters. Conventional imaging studies to assess tumour burden include double contrast cystography and urethrography; however, trans-abdominal ultrasound is now more frequently utilized. Standardization of bladder size for sequential ultrasound measurements to assess tumor response to medical treatment is challenging; however, techniques have been developed and used for TCC chemotherapy clinical trials. Ultrasound is also useful for assessment of tumour involvement of sublumbar lymph nodes and/or abdominal organs. While the majority of TCC cases do not present with obvious metastatic extension to local lymph nodes, lungs or bone, regional and/or distant metastasis will develop in approximately half of cases, and this rate is likely higher for cases that achieve good local tumour control.

Despite the localized nature of most tumours at the time of diagnosis, TCC has typically been treated medically. Surgical removal has generally been considered not feasible due to the common trigone and urethral tumour locations. However, recently veterinary oncologic surgeons have become more interested in attempting total cystectomy with transposition of ureters to the remaining urethra in select cases. Radiation therapy for TCC treatment has also not been a conventional choice due to the side effect profile to normal tissues in the field, such as urethra and colon. These side effects would include colitis and urethritis during and shortly after treatment, with the possibility of stricture in the longer term. As with surgery, radiation therapy is now being utilized more commonly for local control, in both definitive and palliative protocols, likely due to improvements in sparing of normal tissues that surround the bladder, recognition of optimal treatment protocols, and the technology to deliver them. Finally, obstruction of the urethra has conventionally been managed quite successfully with placement of a cystostomy tube. However, recently the placement of urethral or ureteral stents to treat obstruction through an interventional minimally invasive approach is becoming more widely available.

Medical treatment of TCC has included chemotherapy and non-steroidal anti- inflammatory drugs (NSAIDs), such as piroxicam and now other, more cyclooxygenase-2 (COX-2) selective versions, such as deracoxib. At the moment it is not clear how important or relevant COX selectivity may be to the likelihood of treatment response, nor the relative superiority/inferiority of "newer" NSAIDs for TCC treatment. The exact role of COX enzymes in the biology of TCC is an area of ongoing investigation, but previous studies have implicated these enzymes in TCC growth, angiogenesis and apoptosis. The most common chemotherapy protocols have been mitoxantrone, carboplatin, vinblastine, and a few others, including metronomic chlorambucil, often in combination with an NSAID. Nephrotoxicity from platinum drugs in combination with piroxicam limits their application to TCC, despite early studies of high efficacy.

In addition to potential nephrotoxicity from NSAID treatment and chemotherapeutics such as carboplatin, ascending pyelonephritis and obstructive hydronephrosis also pose risks to kidney function during TCC management.

References

1.  Mutsaers AJ, Widmer WR, Knapp DW. Canine transitional cell carcinoma. J Vet Intern Med. 2003;17(2):136-144.

2.  McMillan SK, Boria P, Moore GE, et al. Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder. J Am Vet Med Assoc. 2011;239(8):1084-1089.

3.  Arnold EJ, Childress MO, Fourez LM, et al. Clinical trial of vinblastine in dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med. 2011;25(6):1385-1390.

4.  Henry CJ, McCaw DL, Turnquist SE, et al. Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma. Clin Cancer Res. 2003;9(2):906-911.

5.  Nolan MW, Kogan L, Griffin LR, et al. Intensity-modulated and image-guided radiation therapy for treatment of genitourinary carcinomas in dogs. J Vet Intern Med. 2012;26(4):987-995.

  

Speaker Information
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Anthony J. Mutsaers, DVM, PhD, DACVIM (Oncology)
Ontario Veterinary College
University of Guelph
Guelph, ON, Canada


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