Figure 5. Bone scintigraphy of a 10-year-old female spayed mixed-breed dog with bladder transitional cell carcinoma. This lateral bone scan image is of the right hindlimb and the pelvis, with cranial orientation to the right. Increased radiopharmaceutical uptake in the diaphyses of the tibia and metatarsal area (arrows) suggests bone metastasis (confirmed with radiography and cytology) while increased uptake in the stifle and coxofemoral joints (arrowheads) is compatible with degenerative joint disease.

Surgery

In a retrospective study evaluating various therapies for bladder and urethral tumors, six of 10 dogs with apparent complete surgical resection of their urinary bladder transitional cell carcinoma experienced a local recurrence.¹ Thus, surgery can be used as an emergency therapy to relieve a partial or complete obstruction but is generally only palliative, and owners should understand the high probability of recurrence or metastasis. Ideally, surgical excision of any malignant tumor should be planned with the intent of achieving 1- to 2-cm margins around the visible tumor borders. This is generally impossible in dogs with bladder transitional cell carcinoma.

Tumors located at the bladder's dorsal apex can be treated with partial cystectomy. Other surgical options include placing permanent cystostomy catheters (see "Palliative and supportive therapies") and performing urinary diversion procedures such as a complete cystectomy combined with ureterocolonic anastomosis. These surgical procedures have been used sporadically in veterinary patients, and while a few dogs demonstrated encouraging results, several others suffered considerable postoperative complications.^26,27 Another interesting approach under evaluation to alleviate clinical signs in dogs with urethral or prostatic neoplasia leading to stricture is placing self-expanding metallic stents in the urethra.²⁸

Two recent studies evaluated transurethral resection in dogs with marked urethral involvement. One study that evaluated the use of an electrocautery loop reported a significant risk of complications in female dogs with transitional cell carcinoma, including urethral perforation; male dogs with prostatic carcinoma benefited from this palliative approach.²⁹ The other study used an electrovaporization technique with a rollerball electrode inserted via cystostomy in a small number of healthy dogs.³⁰ This study group experienced a low complication rate and demonstrated the possible applicability of this technique in treating flat or small papillary bladder tumors.³⁰ These minimally invasive surgical techniques warrant further investigation.

Systemic therapy

Systemic treatment of canine transitional cell carcinoma can include nonsteroidal anti-inflammatory drug (NSAID) monotherapy or a combination of chemotherapy and an NSAID.

NSAID monotherapy

The NSAID piroxicam, a nonselective COX inhibitor, has been evaluated as a single agent and in combination protocols for treating canine transitional cell carcinoma. In a prospective clinical trial, piroxicam monotherapy demonstrated an 18% overall objective response rate (6/34), including two complete responses; many patients achieved durable stable disease (minimal or no tumor progression for more than eight weeks).³¹ In addition, since moderate pain or discomfort often accompanies canine transitional cell carcinoma, piroxicam therapy tends to subjectively improve the quality of life and facilitate micturition in most patients, even in the absence of apparent measurable tumor response. The median survival time for the dogs in that study was 181 days.

Recent evidence suggests that COX-2 inhibition may not be the sole factor in the responses observed with piroxicam therapy and that transitional cell carcinoma may not depend on COX-2 for survival. Specifically, it was demonstrated that there is no association among tumor COX-2 expression, tumor PGE₂ concentrations, and response to piroxicam therapy.³² Nevertheless, NSAIDs are a mainstay in treating canine transitional cell carcinoma, and ongoing studies are evaluating veterinary-approved NSAIDs as monotherapy as well as in combination with cytotoxic chemotherapy agents. The precise mechanisms by which NSAIDs exert their antitumor effects remain to be elucidated.