Transitional Cell Cancer of the Renal Pelvis and Ureter

Urothelial Carcinoma, Upper Tract Urothelial Carcinoma

Transitional cell cancer of the renal pelvis and ureter is a rare cancer affecting the upper urinary tract, most commonly diagnosed in adults over age 65. When caught early, it is highly treatable, though it often recurs and requires careful long-term monitoring.

Table of contents

• What Is This Cancer?
• The Renal Pelvis and Ureter
• Causes and Risk Factors
• Signs and Symptoms
• Diagnosis
• Treatment Options
• Outlook and Prognosis

What Is This Cancer?

Transitional cell cancer of the renal pelvis and ureter is a rare cancer that starts in specialized cells lining the upper parts of the urinary tract. These cells are called transitional cells or urothelial cells, and they have a unique ability to stretch and change shape as urine flows through the system^[1].

This cancer accounts for only about 7% of all kidney tumors, and transitional cell cancer of the ureter is even less common, making up only 4% of upper urinary tract tumors^[2]. It is sometimes called upper tract urothelial carcinoma because it occurs in the renal pelvis or ureters, which make up the upper urinary tract^[1].

More than 90% of cancers in these areas come from transitional cells that have become cancerous and grow in an uncontrolled way. When this happens, instead of forming a flat lining, masses form in the urinary tract, which can disrupt urine flow, cause pain, and lead to blockages or bleeding^[1].

This cancer is histologically identical to urinary bladder cancer. Both share the same risk factors and can occur as part of what doctors call “field cancerization,” which results from exposure of the lining to cancer-causing substances that are excreted or activated in the urine^[6].

The Renal Pelvis and Ureter

• Kidney
• Renal pelvis
• Ureter
• Bladder

The renal pelvis is the hollow area at the center of each kidney where urine collects before flowing into the ureters. The ureters are long tubes, about 25 to 30 centimeters (10 to 12 inches) long, that connect each kidney to the bladder^[3].

The kidneys are two bean-shaped organs located on either side of the backbone, above the waist. An adult’s kidneys are about 5 inches long and 3 inches wide. The kidneys play an important role in the urinary system by filtering and cleaning the blood, removing waste products and extra water as urine. The urine collects in the middle of each kidney in the renal pelvis, then passes through the ureter into the bladder. The bladder holds the urine until it passes through the urethra and leaves the body^[3].

The walls of the renal pelvis and ureter are made up of three main layers of tissue. The innermost layer is the urothelium, which contains the transitional cells that line the inside of each renal pelvis and ureter. Beneath this is the lamina propria, a thin layer of connective tissue containing blood vessels, nerves, and glands. The outermost layer is the muscularis propria, a thick muscle layer made up of smooth muscle that pushes urine from the kidney down to the bladder^[4].

Causes and Risk Factors

Doctors do not yet know the exact cause of transitional cell cancer of the renal pelvis and ureter. Though genetics seem to be a factor, it also appears that environmental factors, including smoking and exposure to certain chemicals, raise risk^[1].

Several risk factors have been identified that increase the likelihood of developing this cancer. Cigarette smoking appears to be the most significant acquired risk factor. It is suggested that 70% of upper urinary tract urothelial tumors in men and 40% of those in women can be attributed to smoking^[6].

People who work in certain industries face an increased risk. Workers in the chemical, petrochemical, aniline dye, and plastics industries, as well as those exposed to coal, coke, tar, and asphalt, are at increased risk for renal pelvis and ureteral tumors. People who work with certain chemicals used in dyes, rubber, leather, paint, textiles, and hairdressing supplies may also have an increased risk^[6][1].

Additional risk factors include being male—men are four times more likely to get bladder cancer and twice as likely to develop kidney cancers—and being over age 65, as most people diagnosed are in this age group^[7].

A personal history of bladder cancer significantly increases risk. People who have had bladder cancer are at increased risk of transitional cell carcinoma of the renal pelvis and ureters. In fact, 20% to 48% of patients with upper urinary tract cancer later develop bladder tumors, and 2% to 4% of patients with primary bladder cancer develop upper urinary tract cancer^[6][1].

Lynch syndrome, an inherited genetic condition, also increases the risk of several cancers, including urothelial cancer^[1].

The painkiller phenacetin was once associated with kidney damage that could lead to transitional cell cancer, but it has been off the market since the late 1980s and was not frequently used in the United States. No other painkillers have been associated with this cancer^[1].

Signs and Symptoms

Symptoms may not appear right away, but when they do, blood in the urine is usually the first noticeable sign. Other symptoms of transitional cell cancer of the renal pelvis and ureter include^[1][3]:

• Blood in the urine (which may make urine appear pink, red, or brown)
• Back pain
• Cramps in the side or back
• Fatigue
• Unexplained weight loss
• Pain or burning with urination
• Frequent urination
• A lump or mass in the kidney area (the side and back, between the ribs and hips)
• Persistent low back pain

You should contact a healthcare provider if you notice any of these symptoms, particularly blood in the urine^[7].

Diagnosis

Several tests may be used to diagnose transitional cell cancer of the renal pelvis and ureter. Your doctor will examine you and test your urine for blood. You may also have blood tests to check your general health^[4].

Your doctor may refer you to a specialist called a urologist for further tests. These may include^[4][7]:

• Urinalysis: A test of a urine sample to look for blood or other abnormalities
• Urine cytology: Looking for cancer cells in your urine under a microscope
• CT urogram: A special CT scan using contrast dye to look at the urinary system
• CT scan of the chest: To check whether cancer has spread
• Cystoscopy: Using a thin flexible tube to look inside the bladder
• Ureteroscopy: Using a thin flexible tube to look inside the ureter and kidney to check for abnormal areas
• Biopsy: Taking a small piece of tissue to check for cancer cells
• Intravenous pyelogram (IVP): An X-ray using contrast dye that makes blockages in the kidneys, ureter, and bladder stand out
• MRI or ultrasound: Other imaging tests that may be used to see tumors inside your body

Even when ureteroscopy and pyeloscopy are successfully performed, accurate assessment of how deep the cancer has invaded is difficult^[2].

Treatment Options

Because these upper tract cancers come from the same types of cells that line the bladder, doctors treat them the way they treat bladder cancers, not the way they treat other kidney cancers. There are now a large number of treatments available, ranging from surgery to immune therapies to chemotherapies, including combinations^[1].

Surgery

Surgery is the main treatment for transitional cell cancer of the renal pelvis and ureter. Total excision of the ureter with a bladder cuff, renal pelvis, and kidney—called radical nephroureterectomy—is recommended to provide the greatest likelihood of cure and remains the gold standard of treatment^[2][12].

The surgeon removes the entire kidney, all of the ureter, and the tissue where the ureter connects to the bladder (the bladder cuff). The surgeon may also remove some nearby lymph nodes and surrounding tissue. This surgery is most often done using laparoscopic surgery, where the surgeon makes several small cuts and uses special tools and a camera. Sometimes open surgery is done instead, with a large cut along the side and abdomen^[12].

For small tumors in the lower part of the ureter closest to the bladder, a segmental resection of the ureter may be done. The surgeon removes the part of the ureter with the tumor along with a margin of healthy tissue, then reattaches the ureter to the bladder^[12].

Endoscopic surgery may be done for cancer that is low grade and at an early stage. It may also be done when the kidneys aren’t working well, you only have one kidney, or there is cancer in both sides of the urinary tract. This involves removing the tumor using an endoscope and cutting tools passed through it. Laparoscopic nephroureterectomy is becoming popular, with recurrence rates equivalent to open surgery^[13][12].

Chemotherapy

Chemotherapy uses anticancer drugs to destroy cancer cells. It can be used before surgery (neoadjuvant chemotherapy) or after surgery (adjuvant chemotherapy) to treat cancer that has spread to the lymph nodes or other parts of the body^[12].

Neoadjuvant chemotherapy offers the advantage of using cisplatin-based regimens while patients still have maximal kidney function, before it is reduced by surgery. Adjuvant chemotherapy is generally recommended in select patients with adequate kidney function^[14].

Immunotherapy and Other Treatments

Topical immunotherapy or chemotherapy can be administered to reduce the recurrence rate after endoscopic management of upper urinary tract cancer. Immunotherapy has shown promise but is associated with higher recurrence rates than surgery^[13][14].

The role of radiation therapy in the management of upper urinary tract transitional cell cancer is not well defined. Some studies suggest adjuvant radiation therapy to improve local control after radical surgical treatment for high-grade disease^[14].

Treatment decisions depend on many factors, including the size of the cancer, whether it has spread, how abnormal the cancer cells look, the stage and grade of the cancer, and your overall health^[12].

Outlook and Prognosis

The good news is that when transitional cell cancer of the renal pelvis and ureter is caught early, it is very treatable. These cancers are curable in more than 90% of patients if they are superficial and confined to the renal pelvis or ureter. When the cancer spreads, however, long-term survival rates taper off, depending on how far the cancer has traveled within the body^[1][2].

Patients with deeply invasive tumors that are confined to the renal pelvis or ureter have a 10% to 15% likelihood of cure. Patients with tumors that have penetrated through the urothelial wall or with distant metastases usually cannot be cured with available forms of treatment^[2].

The major prognostic factor at the time of diagnosis is the depth of infiltration into or through the wall. Most superficial tumors are likely to be well differentiated, while infiltrative tumors are likely to be poorly differentiated. The deeper the tumor has grown into the wall, the less favorable the prognosis^[2][24].

The grade of the cancer also affects prognosis. Low-grade cancers do not usually grow into the muscle layer of the wall and do not usually spread to other parts of the body, giving them a good prognosis. High-grade cancers have a greater risk of spreading and a poorer prognosis^[24].

Cancer recurrence is a significant concern. The incidence of subsequent bladder cancer after previous upper tract transitional cell cancer ranges from 30% to 50%. When involvement of the upper tract is diffuse (involving both the renal pelvis and ureter), the likelihood of subsequent bladder cancer increases to 75%^[2].

The incidence of cancer developing in the opposite side (contralateral) upper tract ranges from 2% to 4%^[2]. These cancers often come back, so rigorous and close follow-up is required^[7].