Synopsis

Knapp

An estimated 40,000–60,000 pet dogs will develop urinary bladder cancer each year in the United States. Most bladder cancer in dogs consists of high grade invasive urothelial carcinoma (InvUC). With pronounced cross-species similarities, dogs with InvUC can serve as a highly relevant model for muscle invasive bladder cancer in humans. Depending on the stage of the disease, the treatment for InvUC in dogs can include interventional urology procedures, surgery, radiation therapy, and drugs. This presentation will summarize current and emerging medical therapies for InvUC. Other treatments will be discussed in subsequent presentations.

The medical therapy of InvUC in dogs most often consists of: (1) chemotherapy combined with a cyclooxygenase (COX) inhibitor, or (2) palliative care with single-agent COX inhibitors. Single agent COX inhibitors lead to remission (mostly partial remission) in ~20% of dogs, stable disease in ~55–60% of dogs, and median survival times of 6–7 months. Chemotherapy agents commonly include vinblastine, mitoxantrone, or carboplatin. Results of a prospective trial of vinblastine combined with piroxicam included 58% partial remission, 33% stable disease, median PFI of 199 days, and median survival of 299 days. Interestingly, the median survival in a sequential therapy arm in the trial, i.e., vinblastine alone and then piroxicam alone, was significantly longer at 531 days. In other commonly used therapies, mitoxantrone or carboplatin combined with a COX inhibitor are associated with remission rates of 35–40%. Chlorambucil, lapatinib, palladia, gemcitabine, and other drugs have also been investigated. When first- and second-line therapies are applied, survival can extend from several months to more than a year.

While InvUC is considered “treatable” and can be controlled while maintaining good quality life, it is rarely cured. Resistance to therapy commonly develops over time. Human InvUC is lethal in approximately half of patients, and the need to develop new strategies to improve outcomes in both species is critical. In broad terms, this requires research on multiple fronts including:

1.  Prevention

2.  Early detection and early intervention

3.  Improved application of existing drugs

4.  New targets and targeted therapies

5.  Immunotherapy

6.  Personalized therapy approaches

Work is ongoing on all of these fronts in dogs to benefit dogs and potentially humans with InvUC. Emerging work in dogs that will be discussed in the presentation includes an early intervention study in Scottish terriers, a trial of a BRAF-targeted drug vemurafenib, and characterization of molecular subtypes that differ in cancer behavior and breed.