Transitional cell carcinoma – Basic Information

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Transitional cell carcinoma, also known as urothelial carcinoma, is a cancer that develops in special cells lining parts of the urinary system. While the name may sound technical, this disease affects thousands of people each year and understanding it can make a real difference in catching it early and managing it effectively.

What Is Transitional Cell Carcinoma?

Transitional cell carcinoma is a type of cancer that begins in cells called urothelial cells or transitional cells. These cells have a remarkable ability: they can stretch and change shape, which is why they’re called “transitional.” This special quality is important because these cells line organs that need to expand and contract as they fill with urine and then empty.[1]

These flexible cells create a lining throughout much of your urinary tract. You’ll find them in your bladder, in the part of your kidney called the renal pelvis, and in the ureters, which are the tubes that connect your kidneys to your bladder. The urethra, the tube that carries urine out of your body, also has this lining.[2]

The cancer can develop in any of these locations, though it occurs most commonly in the bladder. When doctors talk about transitional cell carcinoma, they’re describing cancer that starts in these specialized cells and may grow into deeper layers of the organ or spread to other parts of the body if not treated.[1]

Where Does This Cancer Occur?

The bladder is by far the most common site for transitional cell carcinoma. In fact, this cancer makes up about 90% of all bladder cancer cases in the United States. It’s also the most common type of cancer affecting the ureter and accounts for about 95% of bladder cancers overall.[1][4]

When transitional cell carcinoma develops in the kidney, it’s much less common. Only about 5% to 10% of all kidney cancers are transitional cell carcinomas. These typically start in the renal pelvis, which is the central part of the kidney where urine collects before flowing into the ureter.[1][4]

Because the same type of cells line multiple parts of the urinary tract, it’s possible for tumors to develop in more than one location at the same time or one after another. If someone has transitional cell carcinoma in their bladder, doctors will often check other parts of the urinary tract as well.[3]

Epidemiology: Who Gets This Cancer?

Transitional cell carcinoma is the fourth most common cancer in men, though it also affects women, making it the eleventh most common cancer among women. Overall, men are about four times more likely to develop bladder cancer than women. When it comes to kidney cancers including those in the renal pelvis and ureters, men are twice as likely as women to be diagnosed.[1][8]

Age plays a significant role in who develops this cancer. Most people diagnosed with transitional cell carcinoma are over 65 years old. The disease typically affects adults, and it’s quite rare in younger people.[1][5]

There are also differences based on race and ethnicity. White people develop bladder cancer about twice as often as Black people and those of Hispanic descent. Geography matters too, with the incidence varying significantly depending on where people live.[8]

Upper tract transitional cell cancer, which affects the renal pelvis and ureters, is relatively rare. These cancers account for only about 7% of all kidney tumors for renal pelvis cancers and just 4% of upper urinary tract tumors for ureter cancers. They make up roughly 10% of all transitional cell cancers.[5][15]

Causes and How the Disease Develops

Medical researchers don’t know the exact cause of transitional cell carcinoma, but they understand that it happens when a healthy urothelial cell undergoes changes, or mutations, that cause it to become cancerous. When these cells mutate, they start growing and dividing in ways they shouldn’t, eventually forming tumors.[1]

The cancer cells can form tumors that remain on the surface of the bladder or kidney lining, or they can invade deeper into the walls of these organs. Without treatment, cancer cells can break away and spread through the blood or lymphatic system to other parts of the body. This spreading process is called metastasis.[1]

⚠️ Important
Transitional cell carcinoma is strongly linked to environmental factors, particularly exposure to harmful substances. Smoking is thought to cause about half of all bladder cancers. The bladder filters harmful chemicals from cigarette smoke, and over time, this exposure damages the cells lining the bladder, increasing cancer risk significantly. Smokers are three times more likely to develop bladder cancer than non-smokers.[4][6]

Risk Factors: What Increases Your Chances?

Smoking cigarettes is the single biggest risk factor for developing transitional cell carcinoma. The harmful chemicals in tobacco smoke are filtered through the kidneys and stored in the bladder, exposing the urothelial cells to these cancer-causing substances for extended periods.[1][2]

Workplace exposure to certain chemicals significantly increases risk. People who work with chemicals used in making dyes, rubber, leather, paint, textiles, plastics, and printed materials face higher chances of developing this cancer. Workers in hairdressing who regularly use certain products may also be at increased risk.[1][5]

Long-term misuse of certain pain medications, particularly over-the-counter medicines, has been linked to transitional cell carcinoma. The drug phenacetin, which caused kidney damage, was associated with this cancer, but it has been off the market since the late 1980s.[3][5]

Having a personal history of bladder cancer greatly increases the risk of developing transitional cell carcinoma in the upper urinary tract, including the renal pelvis and ureters. Between 30% and 50% of people who’ve had upper tract transitional cell cancer will later develop bladder cancer. If the upper tract involvement is widespread, affecting both the renal pelvis and ureter, the likelihood of later bladder cancer jumps to 75%.[1][15]

Certain genetic conditions also raise risk. People with Lynch syndrome, an inherited condition, have an increased chance of developing several types of cancer, including urothelial carcinoma. Having family members with bladder cancer also makes you more likely to develop the disease.[5][8]

Chronic irritation of the urinary tract can contribute to cancer development. This includes long-term catheter use, such as in people with paraplegia or multiple sclerosis, chronic urinary stone disease, and chronic infections. Previous cancer treatments, including certain chemotherapy drugs like cyclophosphamide and radiation exposure to the pelvic area, also increase risk.[4]

Some research suggests that factors affecting how long urine stays in contact with the bladder lining matter. Long-haul truck drivers and others whose jobs require them to hold urine for extended periods may face higher risk. On the flip side, drinking plenty of fluids and urinating frequently may lower risk by reducing the time harmful substances stay in contact with the urothelial lining.[4]

Symptoms: What to Watch For

Transitional cell carcinoma often doesn’t cause symptoms in its early stages, which is why it sometimes goes undetected initially. As the cancer grows, symptoms develop that should prompt a visit to a healthcare provider.[1]

The most common and often first noticeable symptom is blood in the urine, called hematuria. This blood may make the urine appear pink, red, or cola-colored. Sometimes the blood is only visible under a microscope during a urine test. Blood in the urine is the primary symptom that brings most people with bladder or upper urinary tract cancer to their doctor.[1][2][4]

Changes in urination patterns are also common. This can include needing to urinate more frequently than usual, feeling an urgent need to urinate, or experiencing pain or a burning sensation during urination. These symptoms can be mistaken for a urinary tract infection, which is why proper testing is important.[1][5]

Pain can occur in different areas depending on where the cancer is located. Back pain, particularly persistent pain in the lower back, is common. Some people experience pain or cramping in the side or back, in the area between the ribs and hips, called the flank. A lump or mass in the kidney area might be felt in some cases.[1][5]

General symptoms that can accompany the cancer include fatigue that doesn’t improve with rest and unexplained weight loss. These symptoms tend to appear as the disease progresses.[1][3]

Prevention: Steps to Reduce Your Risk

While not all cases of transitional cell carcinoma can be prevented, there are important steps you can take to significantly reduce your risk. The single most effective prevention strategy is to avoid smoking or to quit if you currently smoke. Because smoking is linked to about half of all bladder cancers, quitting can dramatically lower your chances of developing this disease.[1][4]

If you need help quitting smoking, talk to your healthcare provider about medications or programs that can support you. Many people find that combining medication with counseling or support groups gives them the best chance of successfully quitting for good.[1]

Protecting yourself from harmful chemical exposures is another important prevention measure. If you work with chemicals used in manufacturing dyes, rubber, leather, paint, textiles, or plastics, make sure to follow all safety protocols. Wear protective equipment, ensure good ventilation in your work area, and wash your hands thoroughly after handling these materials.[1][5]

Drinking plenty of fluids, especially water, may help protect your bladder. Aiming for six to eight glasses of water a day helps dilute potentially harmful substances in your urine and reduces the time they’re in contact with the bladder lining. Good hydration means you’ll urinate more frequently, which is actually beneficial.[4]

A healthy diet rich in fruits and vegetables may help keep your urinary tract healthy and could lower your risk of developing bladder and kidney cancers. Try to eat at least five servings of fruits and vegetables daily, and include whole grains in your diet several times a day. A nutrient-rich diet also helps protect against other types of cancer.[4]

Regular physical activity is beneficial not just for cancer prevention but for overall health. Even moderate exercise for 30 minutes a day can make a difference. Talk with your doctor about an appropriate exercise program for you, especially if you haven’t been active recently.[4]

Pathophysiology: How the Disease Affects the Body

Understanding how transitional cell carcinoma changes the normal functioning of the urinary system helps explain why symptoms occur and why treatment is necessary. The disease process begins at the cellular level and can eventually affect the entire urinary tract and beyond.[1]

Normally, the urinary system works like this: Your kidneys filter waste products and excess water from your blood, creating urine. This urine collects in the renal pelvis, the funnel-shaped area in the center of each kidney. From there, urine flows through the ureters into the bladder, where it’s stored until you’re ready to urinate. The urethra then carries urine out of the body.[2]

The urothelial cells that line this system are specially designed to protect the underlying tissues from the toxic components in urine while allowing the organs to expand and contract. In transitional cell carcinoma, these protective cells become abnormal and start multiplying uncontrollably.[1]

Doctors classify transitional cell carcinoma based on how deep the cancer has grown into the organ wall. Superficial tumors remain in the inner lining and haven’t invaded the muscle layer. These are generally well-differentiated, meaning the cancer cells still look somewhat like normal cells under a microscope. Superficial cancers confined to the renal pelvis or ureter can be cured in more than 90% of cases.[15][16]

Invasive tumors have grown through the lining into the deeper muscle layers of the bladder or kidney. These tumors are more likely to be poorly differentiated, meaning the cancer cells look very abnormal and behave more aggressively. When tumors invade deeply but remain confined to the organ, the likelihood of cure drops to about 10% to 15%.[15][16]

Transitional cell carcinoma can be further classified as low-grade or high-grade. Low-grade cancers have cells that look more normal and grow more slowly. They’re less likely to spread into deeper layers or to other parts of the body, and they’re less likely to come back after treatment. High-grade cancers have very abnormal-looking cells that grow rapidly. They’re much more likely to invade deeper tissues, spread to lymph nodes and other organs, and recur after treatment.[3]

When cancer cells break through the organ wall or spread beyond the original site, they can travel through the lymphatic system or bloodstream to distant parts of the body. Common sites for metastasis include the lymph nodes, lungs, liver, and bones. Once the cancer has spread extensively or penetrated through the urothelial wall, it becomes very difficult to cure with currently available treatments.[15][16]

The depth of invasion into or through the urothelial wall is the major factor affecting prognosis at the time of diagnosis. This is why staging, which determines how far the cancer has spread, is so important for planning treatment and understanding what to expect.[15][16]

As tumors grow, they can disrupt normal urine flow, causing pain and potentially leading to blockages. This is why symptoms like back pain and difficulty urinating occur. Tumors can also damage blood vessels in the urinary tract lining, which explains why blood in the urine is such a common symptom. The physical presence of masses in the urinary tract interferes with the normal stretching and contracting that allows urine to move smoothly through the system.[5]

⚠️ Important
Transitional cell carcinoma has a high rate of recurrence, particularly for non-muscle invasive bladder cancers. Up to 70% of these cancers may come back within two years of treatment. This means that even after successful initial treatment, long-term monitoring is essential. People who’ve had upper tract transitional cell cancer have a 2% to 4% chance of developing cancer in the opposite kidney or ureter, and a 30% to 75% chance of later developing bladder cancer, depending on how extensive the original cancer was.[15][20]

Ongoing Clinical Trials on Transitional cell carcinoma

  • A study of SKB410, enfortumab vedotin, and pembrolizumab combination for patients with locally advanced or metastatic urothelial cancer

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    France The Netherlands Spain
  • Study on PET Imaging with Fianlimab and Cemiplimab for Patients with Advanced Solid Tumors, with or without Platinum-Based Chemotherapy

    Recruiting

    2 1 1 1
    Investigated drugs:
    The Netherlands
  • Study of drug combination with gemcitabine, cisplatin, carboplatin and avelumab in patients with advanced urothelial cancer to evaluate response to platinum-based chemotherapy

    Recruiting

    3 1 1 1
    Investigated diseases:
    Italy
  • Study on Chemo-Immunotherapy with Avelumab for Patients with Locally Advanced Urothelial Cancer

    Recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    The Netherlands
  • Study of TYRA-300 in Adults with Low Grade Upper Tract Urothelial Carcinoma to Assess Efficacy and Safety

    Not yet recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Bulgaria France Spain
  • Safety and efficacy study of nadofaragene firadenovec administered to the renal pelvis in adults with low-grade upper tract urothelial carcinoma

    Not yet recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France The Netherlands Spain
  • Study of BT8009 Alone or with Pembrolizumab for Patients with Advanced or Metastatic Bladder Cancer

    Not yet recruiting

    4 1 1 1
    Investigated diseases:
    Spain
  • Study on Pembrolizumab and Cyclophosphamide for Patients with Metastatic Urothelial Cancer

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy
  • Study of BT8009 Alone or with Pembrolizumab for Patients with Advanced or Metastatic Bladder Cancer

    Not recruiting

    4 1 1 1
    Investigated diseases:
    Austria Belgium Bulgaria Czechia Denmark France +12
  • Study of Atezolizumab Treatment Before Surgery in Patients with Bladder Cancer or Upper Urinary Tract Cancer

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    France Spain

References

https://my.clevelandclinic.org/health/diseases/6239-transitional-cell-cancer

https://www.cancer.gov/types/kidney/patient/transitional-cell-treatment-pdq

https://www.webmd.com/cancer/transitional-cell-cancer

https://en.wikipedia.org/wiki/Transitional_cell_carcinoma

https://www.yalemedicine.org/conditions/transitional-cell-cancer-of-the-renal-pelvis-and-ureter

https://www.mayoclinic.org/diseases-conditions/bladder-cancer/symptoms-causes/syc-20356104

https://www.cancerresearchuk.org/about-cancer/upper-urinary-tract-urothelial-cancer

https://www.ebsco.com/research-starters/health-and-medicine/transitional-cell-carcinomas

https://www.cancer.gov/types/kidney/patient/transitional-cell-treatment-pdq

https://www.mayoclinic.org/diseases-conditions/bladder-cancer/diagnosis-treatment/drc-20356109

https://www.ncbi.nlm.nih.gov/books/NBK66044/

https://emedicine.medscape.com/article/281484-treatment

https://www.yalemedicine.org/conditions/transitional-cell-cancer-of-the-renal-pelvis-and-ureter

https://my.clevelandclinic.org/health/diseases/6239-transitional-cell-cancer

https://www.cancer.gov/types/kidney/hp/transitional-cell-treatment-pdq

https://www.ncbi.nlm.nih.gov/books/NBK66010/

https://www.webmd.com/cancer/transitional-cell-cancer

https://my.clevelandclinic.org/health/diseases/6239-transitional-cell-cancer

https://www.cancer.gov/types/kidney/patient/transitional-cell-treatment-pdq

https://www.cxbladder.com/row/blog/managing-life-after-bladder-cancer/

https://www.cancer.org/cancer/types/bladder-cancer/after-treatment/follow-up.html

https://thepatientstory.com/uc-san-francisco/kevin-r/

https://www.regionalcancercare.org/cancer-types/transitional-cell-carcinoma/

https://www.cancer.org.au/cancer-information/types-of-cancer/rare-cancers/upper-tract-urothelial-cancer

FAQ

Why is blood in my urine the main symptom of transitional cell carcinoma?

Blood in the urine, called hematuria, occurs because growing tumors in the bladder, kidney, or ureter can damage blood vessels in the lining of these organs. As the tumor grows, it disrupts the delicate tissue and causes bleeding that mixes with your urine. This is typically the first noticeable sign because even small amounts of blood can change the color of your urine.[1][4]

If I’ve had bladder cancer, am I at higher risk for kidney cancer too?

Yes, having a history of bladder cancer significantly increases your risk of developing transitional cell carcinoma in the upper urinary tract, including the renal pelvis and ureters. This happens because the same type of cells line all these organs. After treatment for upper tract cancer, 30% to 50% of people will later develop bladder cancer, and if both the renal pelvis and ureter were involved, this risk increases to 75%.[1][15]

How much does smoking really increase my risk of bladder cancer?

Smoking dramatically increases your risk of developing transitional cell carcinoma. Smokers are three times more likely to get bladder cancer compared to non-smokers, and smoking is thought to cause about half of all bladder cancer cases. The harmful chemicals in tobacco smoke are filtered through your kidneys and stored in your bladder, exposing the lining to cancer-causing substances for extended periods.[4][6]

Does transitional cell carcinoma of the kidney spread differently than other kidney cancers?

Transitional cell carcinoma of the renal pelvis and ureter behaves more like bladder cancer than like other kidney cancers, because it arises from the same type of cells that line the bladder. Doctors treat upper tract transitional cell cancers using similar approaches to bladder cancer treatment, not like they would treat renal cell carcinoma, which is the most common type of kidney cancer.[5][13]

What does it mean when doctors say transitional cell carcinoma is “high-grade” versus “low-grade”?

Grade refers to how abnormal the cancer cells look under a microscope and how aggressively they behave. Low-grade transitional cell carcinoma has cells that still look relatively normal and grow slowly. These cancers are less likely to spread or come back after treatment. High-grade cancers have very abnormal-looking cells that grow rapidly, are much more likely to invade deeper tissues and spread to other parts of the body, and are more likely to return after treatment.[3][15]

🎯 Key Takeaways

  • Transitional cell carcinoma accounts for about 90% of bladder cancers but only 5-10% of kidney cancers, making bladder involvement far more common.[1]
  • Men are four times more likely than women to develop bladder cancer and twice as likely to develop kidney cancers involving transitional cells.[1]
  • Quitting smoking is the single most effective step you can take to prevent this cancer, as smoking causes about half of all bladder cancer cases.[4]
  • Blood in the urine is usually the first warning sign, though symptoms may not appear until the cancer has grown, making it easy to overlook early disease.[1]
  • When caught early and still superficial, these cancers can be cured in more than 90% of cases, but deeply invasive tumors are much harder to cure.[15]
  • Even after successful treatment, up to 70% of non-muscle invasive bladder cancers may return within two years, requiring long-term monitoring.[20]
  • The cells affected by this cancer can stretch and shrink like an accordion, which is why they’re called “transitional”—they change shape as your bladder fills and empties.[2]
  • Workplace exposure to chemicals in dyes, rubber, leather, paint, and plastics significantly increases your risk, making protective equipment essential for workers in these industries.[1]