Urothelial Carcinoma (Transitional Cell Carcinoma)

Written by Kate Rope
Medically Reviewed by Laura J. Martin, MD on April 30, 2025
11 min read

Urothelial carcinoma is cancer of the urinary system. The urothelium is a kind of epithelial (protective) lining of the urinary system, which includes the urinary tract, bladder, your ureters (the tubes that connect your kidneys to your bladder) and the part of your kidneys that hold urine. The urothelium’s job is to keep your urine from coming in contact with other parts of your body. Carcinoma is the word for cancer that starts in epithelial cells, and it is the most common type of cancer. 

Urothelial carcinoma is also called transitional cell carcinoma because the cells in the urothelium can transition between different shapes to enable the bladder to stretch and shrink as needed. 

Is urothelial cancer the same as bladder cancer? 

Urothelial carcinoma is responsible for 90% of bladder cancer cases. But there are some types of bladder cancer that have different causes, and urothelial carcinoma can also be kidney cancer. Both bladder and kidney cancer are highly treatable when they are caught early. 

Most urothelial carcinoma stays in the lining of the bladder. There are different types of urothelial carcinoma based on how the cancer grows and where it goes. 

Invasive vs. noninvasive urothelial carcinoma. Also called non-muscle invasive, noninvasive urothelial carcinoma grows only in the urothelium. Three-fourths of newly diagnosed bladder cancers are noninvasive. Invasive urothelial carcinoma has spread beyond the bladder lining into the muscle of the bladder. 

High-grade vs. low-grade urothelial carcinoma. “Grade is determined by the pathologist,” says Adam Weiner, MD, a urologic surgeon at Cedars Sinai Medical Center in Los Angeles, California. “The surgeon removes some of the tumor in the operating room using a camera in the bladder. The pathologist looks under a microscope and they can tell based on the size of the cells and some other characteristics that tell them how quickly the cells are dividing.”

In low-grade urothelial carcinoma, the cancer cells look more like the normal cells of the endothelium. They tend to grow slowly and stay within the lining of the bladder. High-grade urothelial carcinoma means the cells look different from normal cells. They tend to grow more quickly and are more likely to spread into the muscle and beyond. 

Flat vs. papillary urothelial carcinoma. Flat urothelial carcinoma is made up of flat cancer cells that sit flush with the bladder wall and are unlikely to become invasive but are likely to come back after treatment. It is also known as carcinoma in situ. In papillary urothelial carcinoma, the cancer cells grow into the space of the bladder in shapes that are described as finger- or mushroom-like. Papillary bladder cancer can be low-grade, high-grade, invasive, or noninvasive. Low-grade, noninvasive papillary urothelial carcinoma is unlikely to return after treatment.

Scientists don’t know exactly what causes urothelial carcinoma (transitional cell carcinoma), but they do know what kinds of things increase your risk of developing it. These include: 

Smoking and using other tobacco products. Smoking is one of the major risk factors for urothelial carcinoma. That’s because tobacco and cigarettes contain harmful carcinogens (cancer-causing chemicals) that are filtered through your blood and end up in your urine. From there, these chemicals can damage your urinary tract lining, making you vulnerable to developing cancer.  

Being exposed to cancer-causing chemicals in your workplace. Research has found that when people are exposed to chemicals that are either in – or used to make – dyes, rubber, some fabrics, leather, and hairstyling supplies, they are more likely to develop urothelial carcinoma. 

Chronic inflammation in your urinary system. Repeated urinary tract infections or bladder catheters can cause inflammation, which increases the risk of cancer by damaging DNA and causing abnormal cells to multiply. 

Radiation therapy. Radiation to treat other cancers near the urinary system, as well as the chemotherapy drug cyclophosphamide, can put you at risk of urothelial carcinoma.

Family history. Having a family history of urothelial carcinoma or the genetic conditions Lynch syndrome and Cowden’s syndrome may predispose you to developing urothelial carcinoma. 

Other things that can increase your risk include being older and being male. Two-thirds to three-quarters of all bladder cancers happen in men. 

“Bladder cancer is most commonly diagnosed by a cystoscopy, a procedure that places a scope [camera] in the bladder and up the ureteral tract (the tube connecting the kidneys to the bladder), where a biopsy can be taken,” says Christina Annunziata, MD, PhD, senior vice president of extramural discovery science at the American Cancer Society. “The biopsy will show whether cancer is present and the type and grade.” This can be done in your doctor’s office. 

If your doctor is fairly certain that you have a tumor in your bladder, it can be removed at the same time as you are diagnosed. This involves a cystoscopy done in the hospital with an additional treatment called transurethral resection of bladder tumor (TURBT), which removes the tumor in full for testing. 

“We usually also try to go into the muscle to see if the cancer has gone into it,” says Weiner. “If the tumor is high grade or muscle invasive, we are going to get a CAT scan of the chest, abdomen, and pelvis to see all areas.” 

The most common symptoms of urothelial cancer are blood in your urine, pain, fatigue, and weight loss. 

Other symptoms of urothelial carcinoma (transitional cell carcinoma) include:

  • Low-grade fever
  • Significant and continuous back pain
  • Painful urination
  • A lump in your kidney area

Some of these symptoms — such as frequent or painful urination — are also symptoms of urinary tract infections in women. So it does happen that women are sometimes incorrectly diagnosed with recurrent urinary tract infections when they have urothelial carcinoma. 

“There are a number of studies that show there is evidence that females are diagnosed with bladder cancer at a later stage relative to their male counterparts,” says Weiner. 

“If a young woman has blood in their urine and then UTI symptoms, we’re going to be less concerned that it's a bladder cancer issue,” says Weiner, “because most bladder cancers occur in older patients.” However, says Weiner, if you are over 60 and not showing signs of bacteria in your urine or improving on antibiotics, it’s reasonable to ask to be referred to a urologist, especially if you have a smoking history.

“Staging refers to the location of the cancer and is typically described as local (in the bladder or ureter only), regional (spread to nearby lymph nodes), or distant (spread to far away lymph nodes or to other organs like lung, liver, bones). Treatment is determined by the stage and grade/type of the cancer,” says Annunziata. 

Here are the stages of urothelial carcinoma or transitional cell carcinoma:

Stage 0 urothelial carcinoma is located only in the lining of the bladder and has not spread into the muscle or anywhere else. Stage 0 urothelial carcinomas come in two types: 0a and 0is. Stage 0a, noninvasive papillary carcinoma, is the kind that grows into the bladder in finger-like shapes. Stage 0is, urothelial carcinoma in situ, is a flat tumor on the lining of the bladder. 

Stage I urothelial carcinoma has spread, but only into the connective tissue that lies under the bladder lining and not into the muscle. 

Stage II urothelial carcinoma is also called muscle invasive bladder cancer because the tumor has gone beyond the connective tissue into the muscle beneath it. 

Stage III urothelial carcinoma has grown further into the body but has stayed in the general area of the bladder. It is also called “locally advanced urothelial carcinoma” and is divided into stage IIIA and stage IIIB. 

  • Stage IIIA urothelial carcinoma has spread beyond the muscle and into the layer of fat that surrounds it. It may also have spread to reproductive organs including the prostate, uterus, or vagina or to just one lymph node in the pelvis.
  • Stage IIIB urothelial carcinoma has either spread to two lymph nodes or one lymph node that is near blood vessels that bring blood to other parts of the body. 

Having cancer cells in more than one lymph node or in lymph nodes near these important arteries means that the cancer is spreading deeper into the body. 

Stage IV urothelial carcinoma is also called metastatic urothelial carcinoma. Metastatic means that the cancer has travelled far from where it started in the body. Stage IV also has two substages: IVA and IVB. Five percent of newly diagnosed bladder cancers are metastatic.

  • Urothelial carcinoma stage IVA has traveled to distant lymph nodes or into the abdominal wall, which is made up of muscles, fat, and tissues and protects the organs inside your abdomen or the pelvic wall, which protects the organs in your pelvis. 
  • Urothelial carcinoma stage IVB has spread to one or more organs in completely different regions of the body such as the lungs or bones. 

There are effective treatments for bladder cancer and, since so many bladder cancers are diagnosed early, many of them are minimally invasive. 

Surgery

There are different levels of surgery to treat bladder cancer that depend on the stage and grade of the cancer. For non-muscle invasive low-grade urothelial carcinoma, providers can usually remove the tumor with a procedure called transurethral resection of bladder tumor (TURBT). The tumor is essentially scraped (and sometimes burned off) from the bladder lining. It can be combined with chemotherapy in the bladder to lessen the likelihood of recurrence. Patients are monitored on a regular basis going forward so that any recurrence can be caught and removed. 

Surgery to remove the bladder, called a cystectomy, is sometimes necessary for muscle-invasive bladder cancer or non-muscle invasive, high-grade urothelial carcinoma that keeps recurring. If the bladder is removed, there are two options to remove urine from the body going forward. 

  • Continent diversion: There are several types of continent diversion procedures.  In one type, surgeons remove a portion of the small intestine and reshape it into a round shape and attach it to the ureters and the urethra. This enables people to go to the bathroom by sitting down on a toilet and relaxing their pelvic floor muscles to release the urine. 
  • Incontinent diversion: This procedure involves removing a smaller section of the small intestine and attaching it to the ureters on one end and the abdominal wall on the other. People wear a sealed plastic bag over the hole in their stomach and under their clothes where urine collects outside their body. To release it, they empty the bag into a toilet. 

 Determining which option is right for you will be a conversation between you and your doctor involving your particular situation and preferences. 

Chemotherapy 

Chemotherapy drugs can be used in a few different ways depending on the stage and grade of bladder cancer. 

After a TURBT procedure, doctors may put chemotherapy drugs directly into the bladder. “We have evidence that if we do a TURBT on a tumor that we suspect is low grade, if we give those patients one dose of chemotherapy into the bladder at the time of the procedure, that can reduce the rate of recurrence,” says Weiner.

Muscle-invasive urothelial carcinoma is usually treated by the infusion of chemotherapy medications through an IV. It may require follow-up radiation or bladder removal if necessary. 

For metastatic urothelial cancer (stage IV bladder cancer), chemotherapy given by IV is usually a required part of more involved treatment. 

Radiation therapy

Radiation therapy to the area of the tumor is used when bladder cancer is muscle invasive and there is a hope of avoiding bladder removal surgery. 

Immunotherapy

Immunotherapy works by prompting someone’s immune system to kick into high gear and fight the cancer cells. There are two ways this works for bladder cancer. One sends immune cells to fight the cancer. The other helps turn off gatekeepers in the immune system called checkpoints. Their role is to keep immune cells from going into overdrive and fighting healthy cells. Checkpoint inhibitors are a new kind of immunotherapy that tells those gatekeepers to step aside and let the immune system go to work. “Giving these prior to surgical removal of the bladder can be really helpful to prevent recurrences later,” says Weiner. 

Immunotherapy is used for high-grade urothelial carcinoma or when there is a large amount of low-grade tumors. Some medications are inserted into the bladder through a catheter in your doctor’s office. It then sits in the bladder for an hour to an hour and a half and then is urinated out. “It really revs up the immune system itself. A bunch of immune cells come to the bladder, see these cells and attack them,” says Weiner. 

Checkpoint inhibitor immunotherapy is usually delivered through an IV and reserved for stage II bladder cancer or higher. “Giving these prior to surgical removal of the bladder can be really helpful to prevent recurrences later,” says Weiner. 

Targeted therapy

Traditional chemotherapy is designed to attack any fast-growing cells, which cancer cells usually are. Targeted therapy is an advancement in cancer treatment that uses medications that are designed to recognize specific kinds of cancer cells and eliminate them in different ways. They are usually used in combination with other treatments. A major study in the New England Journal of Medicine found that patients who received combination immunotherapy and targeted therapy as a first-line treatment had fewer side effects and lived longer than those who received conventional chemotherapy.

In general, urothelial carcinoma is a highly treatable cancer. If found early, the cancer can be removed by surgery and usually will not come back. Patients are also regularly monitored to look for any recurrence and treat it early. 

Here are the five-year survival rates (how many patients will be alive five years after diagnosis) by stage:

  • 97% for noninvasive bladder cancer
  • 71% for cancer that is only found in the bladder (lining or muscles)
  • 39% for bladder cancer that has spread to nearby lymph nodes or organs
  • 8% for metastatic bladder cancer

Urothelial carcinoma (also known as transitional cell carcinoma) makes up most bladder cancers and is highly treatable if caught early. Smoking and being exposed to certain industrial chemicals significantly increase the risk of bladder cancer, which also is more common in men. New advances in immunotherapy are really good news for people who are diagnosed with urothelial cancer. 

Is urothelial carcinoma a fast-growing cancer? 

Urothelial carcinoma can be fast or slow-growing. 

What stage is high-grade urothelial carcinoma? 

The grade of urothelial carcinoma is different than the stage. Stage is determined by whether the cancer has spread beyond the lining of the bladder.

What are the chances of urothelial cancer recurrence? 

The rates of urothelial cancer recurrence are 30% to 60% for noninvasive. Knowing this, your provider will monitor you closely for recurrence so that it will be found early and can be treated successfully. 

Can urothelial carcinoma be cured​? 

While experts do not use the word “cure” with urothelial carcinoma, patients can go into long-term remission.