Rare Classroom: Urothelial Carcinoma

Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Urothelial Carcinoma

Also called transitional cell carcinoma.

What is Urothelial Carcinoma?

  • Urothelial carcinoma is a type of cancer that is found in the urinary tract.
    • It is the most common type of cancer affecting the bladder (around 95 percent of bladder cancer cases), urachus, urethra, and ureter.
  • This is also the second most common form of kidney cancer
    • However, urothelial carcinoma still only accounts for at most ten percent of primary malignant tumors of the kidney.
  • Urothelial carcinoma is also known to affect the prostate
  • This cancer originates in the transitional epithelium. This is a lining of tissue that is present in all of the previously mentioned organs.
  • Urothelial carcinoma is sometimes multi-focal, meaning that patients have more than one tumor at diagnosis in as much as 40 percent of cases.
    • When this cancer spreads, it most often spreads into bone, with the spine most frequently affected.

How Do You Get It?

  • This is a type of cancer that is strongly influenced by environmental risk factors
    • Smoking cigarettes is the strongest risk factor and is believed to play a role an about half of urothelial carcinoma cases
    • Chemical exposure is another significant contributor
      • Industries such as paint manufacturing, petroleum, and agriculture have been implicated.
      • Interestingly, increased fluid consumption can reduce risk because this leads to more passing of urine, leading to reduced ‘dwell time’ of contaminated urine against the urothelial surface
        • In contrast, long haul truck drivers and other positions with longer dwell time increase risk
    • Other risk factors include:
      • Urinary tract infections
      • Chronic catheterization
      • Urinary stone disease
      • Certain drugs
      • Radiation exposure
      • Somatic mutations

What Are The Symptoms?

  • Signs and symptoms of urothelial carcinoma include:
    • Pain in the lower back, typically on one side
    • Bloody urine
    • Difficulty or inability to urinate
    • Painful urination
    • Fatigue
    • Weakness
    • Changes in frequency of urination
    • Swollen feet
    • Appetite loss
    • Unexpected weight loss
    • Bone pain
  • These symptoms are not present in all cases and can vary greatly in severity. This is primary due to differences in the location of the tumor and the extent of the cancer.

How Is It Treated?

  • Urothelial carcinoma can be a challenging cancer to treat
  • In localized, early stage disease, surgical removal of the tumor is a common approach
    • However, recurrence is all too common
    • Mitomycin is often given following surgery
    • Another treatment for localized cancer are infusions of Bacille Calmette-Guérin into the bladder
      • This treatment risks side effects such as tuberculosis or scarring
    • Another approach is cysto-prostatectomy in cases of early muscular invasion
  • In cases of metastasis, chemotherapy is the most common first line treatment
    • Agents used include cisplastin, gemcitabine, methotrexate, adriamycin, and vinblastine, typically in various combinations
    • Vinflunine and taxanes are deployed as a second line therapy
    • Immunotherapies such as pembrolizumab may also be used
  • Most recently, the FDA granted accelerated approval sacituzumab govitecan for locally advanced or metastatic urothelial carcinoma in April of 2021.

Where Can I Learn More???

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