Table 4.

Treatment options for invasive urinary bladder cancer in humans and dogs.

Type of Therapy	Human InvUC	Canine InvUC
Cystectomy	Cystectomy is the frontline treatment of choice in eligible patients with bladder-confined cancer. It is typically combined with neoadjuvant chemotherapy (8, 9)	Cystectomy is not usually performed in pet dogs due to the morbidity and cost of the procedure, and frequent extension of the cancer down the urethra which could preclude surgical cure (30–32)
Radiotherapy	Radiotherapy is used in trimodal therapies (maximum transurethral resection, radiotherapy, chemotherapy) in bladder sparing protocols. This is typically reserved for patients who are not eligible for or choose to forego cystectomy (99)	Studies to determine the efficacy of radiotherapy in dogs are limited. Trimodal therapy has not been investigated in dogs (100–102)
Chemotherapy	Chemotherapy is most often used in the neoadjuvant setting and in the treatment of emergent metastasis. Chemotherapy protocols can include: MVAC (methotrexate, vinblastine, doxorubicin, cisplatin), or in recent years less toxic combinations such as cisplatin-gemcitabine or carboplatin-taxol (103, 104)	Since cystectomy is rarely performed in dogs, chemotherapy is used to treat the primary cancer in the urinary tract, as well as to treat metastasis. Chemotherapy drugs with activity in dogs include: cisplatin, carboplatin, vinblastine, mitoxantrone, and others. Cisplatin is considered one of the most active agents in humans and dogs, but is rarely used in dogs due to consistent renal toxicity (10, 30)
Cyclooxygenase (Cox) inhibitors	Cox inhibitors are not routinely used as anticancer agents in human bladder cancer. In humans, Cox inhibitors induce biological changes in tumor tissues similar to those noted in canine bladder cancer (105, 106)	Cox inhibitors are a mainstay of canine bladder cancer treatment. These drugs are appealing because of the antitumor effects (single agent remission rate 20%, stable disease rate 55–60%), oral delivery, relatively low cost and risk of side effects, and positive benefits on quality of life. Cox inhibitors are also used to improve remission rates with chemotherapy, e.g., doubling the remission rate with cisplatin and vinblastine (30, 107–112)
Immunotherapy	Immune checkpoint inhibitors approved for use in humans include those targeting PD-L1 (atezolizumab, durvalumab, avelumab) and those targeting PD-1 (pembrolizumab, nivolumab) (12, 113–120)	Immune checkpoint inhibitors are not yet available for use in dogs
Targeted agents	An FGFR inhibitor (Erdafitinib) is approved for use in human bladder cancer	FGFR mutations are less common in canine bladder cancer, and agents targeting FGFR have not been tested in dogs. Targeted therapies tested in dogs include an EGF-toxin conjugate, and folate targeted therapies (78, 121, 122)