Transitional cell carcinoma (TCC), also known as urothelial carcinoma (UC), is the most common malignant tumor of the canine urinary tract, accounting for approximately 1.5-2% of all canine cancers.
Overview and Clinical Importance
Transitional cell carcinoma (TCC), also known as urothelial carcinoma (UC), is the most common malignant tumor of the canine urinary tract, accounting for approximately 1.5-2% of all canine cancers. This aggressive neoplasm arises from the transitional epithelium lining the urinary bladder and frequently involves the trigone region, making complete surgical excision challenging.
TCC in dogs is considered a highly relevant comparative model for human invasive bladder cancer, sharing similar molecular features. The disease typically presents with clinical signs mimicking urinary tract infection, often leading to delayed diagnosis.
| Breed |
Relative Risk |
BRAF Mutation Prevalence |
| Scottish Terrier |
18-20x increased |
73% (highest) |
| West Highland White Terrier |
3-6x increased |
High |
| Shetland Sheepdog |
3-6x increased |
High |
| Beagle |
3-4x increased |
Moderate |
Etiology and Risk Factors
Breed Predisposition
Certain breeds demonstrate significantly increased risk. The Scottish Terrier has the highest breed-associated risk, approximately 18-20 times greater than mixed breed dogs.
High-YieldOn the NAVLE, when you see a Scottish Terrier with hematuria and stranguria that fails to respond to antibiotic therapy, TCC should be your top differential diagnosis.
Environmental and Host Risk Factors
NAVLE TipFeeding vegetables at least 3 times weekly has been associated with a 70% reduction in TCC risk in Scottish Terriers.
| Risk Factor |
Clinical Significance |
| Female sex |
Female:male ratio 1.7-1.95:1; possibly due to less frequent urination |
| Obesity |
Significantly increases TCC risk |
| Phenoxy herbicides |
Lawn chemical exposure increases risk |
| Cyclophosphamide |
Prior chemotherapy is a documented risk factor |
| Age |
Mean age at diagnosis: 11 years |
Pathophysiology
Tumor Characteristics
Canine TCC is typically a high-grade, papillary infiltrative tumor. Key features:
- Trigone predilection: Approximately 85% of tumors involve the trigone region
- Urethral involvement: Present in 56% of dogs at diagnosis
- Prostatic involvement: Occurs in 29% of male dogs (worse prognosis)
- Metastatic disease: Present in 16-20% at diagnosis; greater than 50% at death
- Common metastatic sites: Regional lymph nodes (iliac), lungs, liver, bones
BRAF Mutation (V595E)
Approximately 85% of canine TCCs harbor the BRAF V595E mutation. This mutation:
- Causes constitutive activation of the MAP kinase signaling pathway
- Is NOT present in benign conditions (polyps, cystitis)
- Terriers have higher BRAF mutation prevalence (73%) vs non-terriers (36%)
- Forms the basis of the CADET BRAF urine test
| Clinical Sign |
Clinical Significance |
| Hematuria |
Most common presenting sign |
| Stranguria |
Straining to urinate; partial obstruction |
| Pollakiuria |
Frequent urination of small volumes |
| Recurrent UTI |
55% have concurrent UTI; temporary antibiotic response delays diagnosis |
| Urinary obstruction |
Life-threatening emergency; most common cause of death |
Clinical Signs and Presentation
Clinical signs are non-specific and closely mimic UTI.
High-YieldPersistent or recurrent LUTS despite appropriate antibiotic therapy should prompt TCC evaluation.
| Parameter |
Value |
| Sensitivity |
85% (with BRAF-Plus: greater than 95%) |
| Specificity |
Greater than 99% |
| Sample |
Free-catch urine (30-40 mL); NOT cystocentesis |
| Interference |
NOT affected by hematuria, pyuria, or bacteriuria |
| Positive result |
Greater than 99% probability of TCC; can substitute for biopsy |
| Negative result |
Does NOT rule out TCC (15% lack BRAF mutation) |
Diagnostic Approach
Exam Focus: AVOID CYSTOCENTESIS in suspected TCC! TCC can seed along needle tracts. This is critical for NAVLE.
BRAF Mutation Test (CADET BRAF)
The CADET BRAF test is a non-invasive, highly specific urine test.
High-YieldBRAF positive = TCC confirmed. BRAF negative = further workup needed (does NOT rule out TCC).
Abdominal Ultrasound
Ultrasound is the first-line imaging modality for detecting bladder masses.
| Finding |
Significance |
| Trigone location |
Most common; shorter survival vs apex |
| Wall involvement |
93% sens, 92% spec for muscle invasion |
| Heterogeneous mass |
Shorter survival vs homogeneous |
WHO TNM Staging
Higher TNM stage correlates with shorter survival.
| Stage |
Description |
Prevalence |
| T1 |
Papillary, lamina propria only |
Rare (less than 5%) |
| T2 |
Invading muscle layer |
Most common (78%) |
| T3 |
Invading neighboring organs |
20% at diagnosis |
| N0/N1 |
No/Regional lymph node metastasis |
N1: 70d vs N0: 234d survival |
| M0/M1 |
No/Distant metastasis |
M1: 105d vs M0: 203d |
Treatment Options
Treatment is primarily medical (palliative) due to trigonal location.
High-YieldAVOID combining piroxicam with cisplatin - causes significant renal and GI toxicity. Piroxicam is safe with mitoxantrone and vinblastine.
| Protocol |
Response |
Survival |
Notes |
| Piroxicam alone |
18-20% |
5.9 months |
0.3 mg/kg PO daily |
| Vinblastine + Piroxicam |
58% |
299 days |
First-line |
| Mitoxantrone + Piroxicam |
35% |
291-350 days |
5mg/m2 IV q3wks |
| Carboplatin + Piroxicam |
13-38% |
161-263 days |
Higher GI toxicity |
Prognosis
Prognosis is guarded to poor. Most dogs die from urinary obstruction.
| Factor |
Survival |
| No treatment |
109 days |
| With treatment |
6-12 months |
| Prostatic involvement |
6 months (worse) |