Transitional cell carcinoma


Transitional cell carcinoma, also called urothelial carcinoma, is a type of cancer that typically occurs in the urinary system. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. It is the second most common type of kidney cancer, but accounts for only five to 10 percent of all primary renal malignant tumors.
Transitional cell carcinomas arise from the transitional epithelium, a tissue lining the inner surface of these hollow organs.
When the term "urothelial" is used, it specifically refers to a carcinoma of the urothelium, meaning a transitional cell carcinomas of the urinary system.

Signs and symptoms

Signs and symptoms of transitional cell carcinomas depend on the location and extent of the cancer.

Causes

Urothelial carcinoma is a prototypical example of a malignancy arising from environmental carcinogenic influences. By far the most important cause is cigarette smoking, which contributes to approximately one-half of the disease burden. Chemical exposure, such as those sustained by workers in the petroleum industry, the manufacture of paints and pigments, and agrochemicals are known to predispose one to urothelial cancer. The risk is lowered by increased liquid consumption, presumably as a consequence of increased urine production and thus less dwell time on the urothelial surface. Conversely, risk is increased among long-haul truck drivers and others in whom long urine dwell-times are encountered. As with most epithelial cancers, physical irritation has been associated with increased risk of malignant transformation of the urothelium. Thus, urothelial carcinomas are more common in the context of chronic urinary stone disease, chronic catheterization, and chronic infections. Some particular examples are listed below:
  1. Certain drugs, such as cyclophosphamide, via the metabolites acrolein and phenacetin, may predispose to the development of transitional cell carcinomas.
  2. Radiation exposure
  3. Somatic mutation, such as deletion of chromosome 9q, 9p, 11p, 17p, 13q, 14q and overexpression of RAS and epidermal growth factor receptor.

    Pathology

Transitional cell carcinomas are often multifocal, with 30–40% of patients having more than one tumor at diagnosis. The pattern of growth of transitional cell carcinomas can be papillary, sessile, or carcinoma in situ. The most common site of transitional cell carcinoma metastasis outside the pelvis is bone ; of these, 40 percent are in the spine.

Diagnosis

Transitional refers to the histological subtype of the cancerous cells as seen under a microscope.

Classification

The 1973 WHO grading system for transitional cell carcinomas is most commonly used despite being superseded by the 2004 WHO grading.

Treatment

Localized/early transitional cell carcinomas of bladder

Transitional cell carcinomas can be very difficult to treat. Treatment for localized stage transitional cell carcinomas is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period or a few weeks after the surgery as a six dose regimen.
Localized/early transitional cell carcinomas can also be treated with infusions of Bacille Calmette–Guérin into the bladder. These are given weekly for either 6 weeks or 3 weeks. Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to BCG, causing severe intolerance and a possible reduction in bladder volume due to scarring.
In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.

Advanced or metastatic transitional cell carcinomas

First-line chemotherapy regimens for advanced or metastatic transitional cell carcinomas consists of gemcitabine and cisplatin) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin.
Taxanes or vinflunine have been used as second-line therapy.
Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.
In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. The confirmatory trial failed to achieve its primary endpoint of overall survival.

Prostate

Transitional cell carcinomas can also be associated with the prostate.