Canine Transitional Cell Carcinoma

Definition

• Transitional Cell Carcinoma (TCC): A malignant neoplasm affecting the urinary bladder, commonly seen in dogs. It represents 1.5–2% of all canine cancers and is the most frequent urinary tract cancer in dogs.

Etiology and Risk Factors

• Multifactorial etiology:

  • Breed predisposition: High risk in Scottish Terriers, Beagles, Shetland Sheepdogs, West Highland White Terriers, and Wire Hair Fox Terriers.

  • Sex: Increased prevalence in females, with a female-to-male ratio of 1.7:1.

  • Environmental exposure: Insecticides used for flea and tick control, particularly in marsh areas sprayed for mosquitoes.

  • Obesity: Overweight dogs have a higher risk.

  • Cyclophosphamide exposure: Increases the risk due to sterile hemorrhagic cystitis, leading to chronic irritation of the bladder.

Pathophysiology

• Tumor characteristics:

  • Predominantly papillary infiltrative TCC with intermediate to high-grade malignancy.

  • High frequency of aneuploidy (79% of cases).

  • Cyclooxygenase-2 (COX-2) is overexpressed in TCC, leading to increased Prostaglandin E2 (PGE2), which promotes tumor growth through inflammation, immunosuppression, and angiogenesis.

Clinical Signs

• Common signs:

  • Hematuria (presence of blood in urine)

  • Stranguria (painful urination)

  • Dysuria (difficulty urinating)

  • Pollakiuria (frequent urination)

  • Less common signs: Lameness, lethargy, weight loss.

Diagnostic Tests

• Imaging:

  • Ultrasonography: Superior for imaging bladder masses, staging lymph nodes, and abdominal organs. Contrast cystography is also used but less effective than ultrasonography.

  • TNM staging: Tumor-node-metastasis classification is vital for prognosis.

• Biopsy:

  • Required for a definitive diagnosis through cystotomy, cystoscopy, or catheter biopsy.

• Urine Tests:

  • Bladder Tumor Antigen (BTA) Test: High sensitivity (90%) and specificity (78%) for detecting TCC.

Staging

• TNM Classification:

  • T: Primary tumor staging, ranging from carcinoma in situ (Tis) to tumor invasion into neighboring organs (T3).

  • N: Lymph node involvement, from no involvement (N0) to juxtaregional lymph node involvement (N2).

  • M: Metastasis, from no evidence (M0) to distant metastasis present (M1).

Prognosis

• Factors influencing prognosis:

  • TNM stage: Advanced stage at diagnosis correlates with shorter survival.

  • Urethral involvement and vascular invasion: Indicators of metastasis and poorer prognosis.

  • Histologic features: Glandular differentiation and T3 stage associated with poor response to treatment.

Treatment Options

1. Surgery:

   • Partial cystectomy: Limited success due to the trigonal location of most tumors and high recurrence rates.

   • Debulking surgery: Often used in combination with medical therapies but rarely achieves complete remission.

2. Radiation Therapy:

   • Palliative care: External beam radiation therapy combined with mitoxantrone and piroxicam can provide clinical improvement.

3. Chemotherapy:

   • Cisplatin: 12-20% response rate, though nephrotoxicity is common.

   • Carboplatin: Similar to cisplatin but with less nephrotoxicity.

   • Mitoxantrone: Used in combination protocols, providing longer survival times.

   • Piroxicam (NSAID): Shows efficacy as a monotherapy or in combination with platinum-based chemotherapies, especially in inducing tumor remission through apoptosis.

4. Emerging Therapies:

   • Photodynamic therapy: Preclinical studies show promise in non-tumor-bearing dogs.

   • COX-2 inhibitors: Continued research into combining these with other therapies to enhance treatment outcomes.

Complications and Management

• Urinary obstruction: A common complication, often leading to death if not managed with cystostomy catheters or other palliative procedures.

• Metastatic disease: Common sites include lungs, lymph nodes, and liver, making monitoring and early intervention crucial.

Comparative Aspects

• Canine TCC as a Model for Human TCC:

  • Similarities: Both species show similar histopathologic and molecular features, such as COX-2 overexpression and PGE2 elevation. Gender predilections differ (males more affected in humans, females in dogs).

  • Clinical implications: Research in canine TCC can provide insights and potential therapies for human bladder cancer.

Reference:

Anthony J. Mutsaers. Canine Transitional Cell Carcinoma. J Vet Intern Med 2003;17:136–144