|Other names: Transitional cell carcinoma (TCC)|
|Histopathology of transitional carcinoma of the urinary bladder. Transurethral biopsy. Hematoxylin and eosin stain.|
|Symptoms||Blood in the urine, back pain, weight loss, pain with urination|
|Complications||Spread to other parts of the body|
|Types||Upper tract, urinary bladder|
|Risk factors||Smoking, aromatic amines, arsenic, aristolochic acid, Lynch syndrome|
|Diagnostic method||Cystoscopy and biopsy|
|Treatment||Surgery, chemotherapy, laser surgery|
|Prognosis||Good if found early|
Urothelial carcinoma, previously called transitional cell carcinoma, is a type of cancer that can occur anywhere along the urinary tract. This includes the kidneys, ureters, bladder, prostate, and urethra. Symptoms may include blood in the urine, back pain, weight loss, or pain with urination.
Risk factors include smoking, aromatic amines, arsenic, aristolochic acid, Schistosoma haematobium, and genetic disorders such as Lynch syndrome. They develop from the transitional epithelium. The diagnosis is generally confirmed by cystoscopy and biopsy.
Treatment often include surgery. Other options may include chemotherapy or laser surgery. If the cancer remains localized a cure if often possible. Multiple areas of the urinary tract; however, may be affected and there is a risk of reoccurrence. Spread may also occur to lymph nodes, lung, liver, or bone.
Urothelial carcinomas make up about 12.5% of cancer cases. Males are more commonly affected than females. They are the most common cancer of the urinary tract, representing more than 90% of bladder cancers and about 7% of kidney cancers. They are the second most common reason for death from genitourinary cancers.
Signs and symptoms
Symptoms of transitional cell carcinomas depend on the location and extent of the cancer.
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 (e.g., aniline dyes), 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 (as in patients with paraplegia or multiple sclerosis), and chronic infections. Some particular examples are listed below:
- Certain drugs, such as cyclophosphamide, via the metabolites acrolein and phenacetin, may predispose to the development of transitional cell carcinomas (the latter especially with respect to the upper urinary tract).
- Radiation exposure
- Somatic mutation, such as deletion of chromosome 9q, 9p, 11p, 17p, 13q, 14q and overexpression of RAS (oncogene) and epidermal growth factor receptor (EGFR).
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 (35%); of these, 40 percent are in the spine.
Transitional refers to the histological subtype of the cancerous cells as seen under a microscope.
The 1973 WHO grading system for transitional cell carcinomas (papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO grading (papillary neoplasm of low malignant potential [PNLMP], low grade, and high grade papillary carcinoma).
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 people are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) 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 (induction course) or 3 weeks (maintenance/booster dose). 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 people 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.
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.
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 (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival.
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