Transitional Cell Carcinoma

Transitional cell carcinoma (TCC), also known as urothelial carcinoma, is a common malignancy predominantly affecting the urinary system, including the bladder, ureter, urethra, and urachus.

It arises from the transitional epithelium lining these organs and is notably the most common type of bladder cancer. Men, older individuals, smokers, and those exposed to specific chemicals are at higher risk.

Signs and Symptoms

The primary symptom of bladder cancer, including TCC, is hematuria, or blood in the urine. The clinical presentation can vary depending on the location and extent of the cancer, but hematuria remains a significant indicator.

Causes

TCC is strongly associated with environmental carcinogenic influences, with cigarette smoking being the most significant risk factor, contributing to roughly half of the disease burden. Chemical exposures, such as those involving workers in the petroleum industry and the manufacture of paints and pigments, also increase risk. Chronic physical irritation from urinary stones, catheterisation, and infections can predispose individuals to TCC. Certain drugs like cyclophosphamide and radiation exposure are additional risk factors.

Growth and Spread

TCCs often present as multifocal tumours, with 30–40% of patients having multiple tumours at diagnosis. The growth patterns can be papillary, sessile, or carcinoma in situ. The most common site for metastasis outside the pelvis is bone, particularly the spine.

Diagnosis

Diagnosis of TCC involves urine analysis and imaging of the urinary tract, typically through cystoscopy. Histologically, TCCs are identified by their transitional epithelium origins.

Immunohistochemistry for p53 can help distinguish between different grades of TCC, with overexpression seen in 75% of low-grade urothelial carcinomas.

The 1973 WHO grading system for TCCs is still commonly used, categorising tumours as papilloma, G1, G2, or G3. The 2004 WHO grading system includes papillary neoplasm of low malignant potential (PNLMP), low grade, and high-grade papillary carcinoma.

Treatment

Localised/Early Transitional Cell Carcinomas of Bladder

Localised TCCs are primarily treated through surgical resection, with recurrence being common. Mitomycin may be administered into the bladder post-operatively. Bacille Calmette–Guérin (BCG) infusions are another treatment option, although they carry risks of systemic tuberculosis and bladder scarring.

For early muscular invasion, radical surgery such as cysto-prostatectomy with lymph node sampling is performed. Urine storage post-surgery can be managed using a neo-bladder or an ileal conduit.

Advanced or Metastatic Transitional Cell Carcinomas

First-line chemotherapy for advanced TCC includes gemcitabine and cisplatin or MVAC (methotrexate, vinblastine, adriamycin, cisplatin). Second-line therapies include taxanes or vinflunine and immunotherapy, such as pembrolizumab.

In recent advancements, the FDA has approved atezolizumab and sacituzumab govitecan for advanced TCC, although confirmatory trials for atezolizumab have not shown significant overall survival benefits.

Prostate

TCC can also affect the prostate, contributing to the complexity of diagnosis and treatment in affected individuals.

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Self-assessment MCQs (single best answer)

What is the most significant risk factor for developing transitional cell carcinoma (TCC)?

What is the most common symptom of transitional cell carcinoma?

Which of the following organs is NOT typically affected by transitional cell carcinoma?

What percentage of patients present with multiple tumours at the diagnosis of TCC?

Which histological technique can help distinguish between different grades of TCC?

Under the 1973 WHO grading system, what is the highest grade of TCC?

What is a common first-line chemotherapy treatment for advanced TCC?

Which FDA-approved drug for advanced TCC did not show significant overall survival benefits in confirmatory trials?

What surgical procedure is performed for early muscular invasion of TCC?

Which of the following is a potential risk associated with Bacille Calmette–Guérin (BCG) treatment for TCC?