Urothelial Carcinoma

Most common type of cancer affecting the bladder.

Epidemiology

80% of patients are between 50 and 80 years old. (1)
Affect males more than females. (1,2)
Caucasians are most prone to urothelial carcinoma. (1,2)

Risk Factors

Smoking. (2)
Cyclophosphamide treatment. (2)
Radiation treatment. (2)
Industrial chemicals and pollutants. (2)
Certain jobs with exposure to chemicals. (3)

Jobs that are at risk for urothelial carcinoma (3):

Dye manufactures due to exposure to aromatic amines.
Construction worksers due to exposure to coal.
Fire fighters due to exposure to polyaromatic hydrocarbons.

Signs & Symptoms

Hematuria (blood in urine). (2)
Frequent urination. (4)
Painful urination. (2)
Back pain. (4)

For diagnosis, urinalysis is done to check for presence of blood in the urine. Cystoscopy allows the doctors to examine the inside of the bladder for signs of the disease. Biopsy can also be taken to observe structural alterations. (4)

Pathogenesis

2 distinct precursors lead to different morphology.
- Papilloma is the more precursor, it gives rise to papillary carcinoma. (1)
- Carcinoma in situ is flat and high-grade, its precursor is usually overgrown. (1)
Acquired genetic mutations. (1)

Molecular pathogenesis:

Papillary tumor -- usually starts with a deletion in tumor suppressor gene on chromosome 9 which causes the formation of papilloma. Then, loss of function of another tumor suppressor gene called TP53 allows the tumor to be invasive. (1)
Flat carcinoma -- TP53 mutation leads to carcinoma in situ. The mutation on chromosome 9 then makes it invasive.
Other mutated genes include FGFR3, RAS, and PI3K/AKT pathway. (1)

Flat

Always high grade. (2)
Without treatment, carcinoma in situ will likely to become invasive. (2)

(5)

Papillary

Tree-like appearance. (1,2)
Grading of papillary carcinoma (2):
- Papilloma is benign.
- PUNLIMP is becoming malignant, but not cancer yet.
- LGUC is low grade with 2% to 3% rate of death.
- HGUC is high grade with 20% rate of death.

(6)

Treatment & Prognosis

Low-grade papillary carcinoma can be treated with transurethral resection. (1)
BCG is used for tumor with high risks of recurrence and progression. (1)
For high-grade invasive tumor, radical cystecomy (bladder removal, may include adjacent lymph nodes) is needed. (1)

BCG therapy involves using attenuated strain of Tuberculosis bacillus to stimulate the local immune system to attack the tumor. Sometimes coupled with intravesical chemotherapy. (2)