Key Points

• The majority of lower urinary tract tumors are malignant, with transitional cell carcinoma (TCC) the most common.
• If bladder cancer is suspected, urine should not be collected via cystocentesis, since the procedure can cause seeding and transplant tumor to unaffected abdominal sites. Percutaneous aspirates and biopsies should also be avoided.
• Since the trigone lesion is most common, complete surgical excision is unlikely.
• Medical management is the mainstay for TCC therapy. Mitoxantrone and NSAID therapy is well tolerated and can cause reduction in tumor size, palliation and improvement of clinical signs, and increased survival times.

Lower urinary tract tumors are relatively rare in dogs, estimated to be less than 2% of reported tumors. The most common malignancy is transitional cell carcinoma (TCC), which is most commonly located in the trigone area. Fifty percent of dogs will have urethral involvement from extension of the primary bladder mass.

TCC is usually highly invasive in dogs. Problems associated include clinical signs of lower urinary tract disease which is troubling to dogs and owners. The cancer can lead to urinary tract obstruction and distant metastases in >50% of dogs. Risk factors include exposure to older flea control product and lawn chemicals, obesity, female sex, and a very strong breed-associated risk. A 2013 study demonstrated that dogs could be exposed to chemicals through contact with their own lawn (treated or contaminated by drift) or through contact with other grassy areas if they travel. Clients should be aware that neighbor’s lawn chemicals can contaminate their property. Feeding vegetables may help prevent TCC.

The veterinary bladder tumor antigen test (VBTA) is 85% sensitive for TCC but only 45% specific in the presence of other urinary tract disease (hematuria, pyuria). It can be used as a screening test and a negative result is 85% reliable but a positive result does NOT equal TCC.

In general, surgery is considered palliative because of the high metastatic rates and because normal tissue often contains neoplastic or pre-neoplastic tissue. Visual assessment at the time of cystectomy is often inaccurate for achieving tumor-free margins. Wide surgical excision is imperative. Even with complete resections, TCC recurrence is likely, either due to microscopic cells at the margins or development of de novo tumors. Surgery reduces clinical signs but may not extend survival.

Medical management is the mainstay for TCC therapy. Although TCC is typically not curable, treatment is often well tolerated, so treated dogs live longer AND live well. Approximately 75% of dogs respond favorably to treatment and can enjoy several months to a year or more of good-quality life.

Several drug combinations and protocols have been evaluated. The most commonly used protocol is mitoxantrone and piroxicam. Overall response rate is 35% with a MST of 350 days. 75% of the 49 dogs had clinical improvement even if the tumor did not have measurable remission. Gastrointestinal and renal toxicity was low and reported at <15%. In contrast, the MST with piroxicam alone is approximately 6 to 7 months, and the MST with surgery alone is approximately 3.5 months.

Cisplatin has also been evaluated with NSAIDs, but this protocol is not recommended. Cisplatin can be nephrotoxic, and NSAIDs can exacerbate renal toxicity.

Additional research has evaluated newer NSAIDs that are more COX-2 selective. In 2011, deracoxib (Deramaxx), a selective cyclooxygenase-2 inhibitor, was evaluated in 26 dogs with bladder TCC. Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d as a single­ agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC. Firocoxib (Previcox) has also been evaluated.

In 2011, vinblastine was evaluated in 28 dogs with tumor responses of 36% partial response, 50% stable disease and 14% progressive disease. Treatment was well tolerated in in 27 of 28 dogs. Median survival time (MST) was 147 from 1st vinblastine to death and 299 days from diagnosis to death. Vinorelbine has also been evaluated as rescue therapy in 13 dogs. Two dogs (14%) had partial response and 8 (57%) had stable disease. Subjective improvement was noted in 11 dogs (78%). Median progression free interval was 93 days (20–239 d). MST was 187 days and MST of pre-treated dogs was 207 days.

In 2013, metronomic (low dose oral) administration of chlorambucil has also been evaluated (4 mg/m² PO q 24 hours). 29 of 31 dogs had failed previous treatment. Of 30 dogs, 1 dog (3%) had partial response, 20 (67%) had stable disease, and 9 (30%) had progressive disease. Median progression free interval was 119 days (7–728 d). MST was 221 days (7–747 d) from start of chlorambucil. Treatment was well tolerated and only discontinued due to toxicity in one dog. 70% had partial response or stable disease.

In 2015, a study compared piroxicam in combination with mitoxantrone or carboplatin in 50 dogs, and the response was not different between the groups. None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone=106 days; carboplatin=73.5 days). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively).

In 2016, a pilot study evaluated 5 dogs receiving vinblastine at 1.6 mg/m² every 2 weeks and toceranib (Palladia) at 2.5–2.75 mg/kg on Monday/Wednesday/Friday. Tumor monitoring was achieved through CT and abdominal ultrasound (AUS). Both imaging modalities were found to provide repeatable measurements between operators; however, agreement between operator measurements was greater when CT images were used to assess tumor size. The combination of toceranib and vinblastine did not result in improved response rates but there were only 5 dogs. While agreement in tumor volume assessments between both AUS and CT was excellent between operators, this did not extend to assessment of tumor response. The higher rate of concordance between operators when assessing response to treatment with CT suggests that CT should be considered for future clinical trials involving canine bladder TCC to improve the accuracy and repeatability of tumor measurement. The data suggest that response to therapy as assessed by AUS or CT does not predict duration of clinical response.

References

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8.  Knapp OW et al. Detection of herbicides in the urine of pet dogs following home lawn chemical application. Sci Total Environ. 2013;456–457:34–41.

9.  McMillan SK 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.

10.  Rippy SB et al. A pilot study of toceranib vinblastine therapy for canine transitional cell carcinoma. BMC Vet Res. 2016;12(1):257.

11.  Schrempp OR et al. Metronomic administration of chlorambucil for treatment of dogs with urinary bladder transitional cell carcinoma. J Am Vet Med Assoc. 2013;242(11):1534–1538.