Kidney, Urethral or Ureteral Cancer

Under normal circumstances, the kidneys work like clockwork, cleaning the blood and removing wastes from the body. The cells lining the urinary tract are called urothelial cells. But what happens when the urothelial cells lining of the urinary tract multiply uncontrollably and form tumors? Although blood in your urine or pain in your side may signal a benign problem, it could mean a malignancy or an urothelial cancer. The information below should help you understand cancer of the ureter and renal pelvis.

What happens under normal conditions?

The kidneys are the body’s sophisticated filtering system. These two bean-shaped organs, located near the middle of the back below the rib cage, filter about 200 quarts of blood daily to sift out about two quarts of extra water and waste products as urine. The actual processing occurs in millions of tiny units, called nephrons, which contain equally tiny blood vessels, glomeruli and urine-collecting tubules. Together, they host a complicated chemical exchange in which nutrients are recaptured for the body while waste products and water are filtered from the blood. The resulting urine is then transported into the kidney’s collecting system – the renal pelvis – before moving through the ureters to the bladder, where it is stored until being pushed out the urethra.

What is upper urinary tract cancer?

It is a disease in which cancer cells are found in the tissues of the kidneys, the renal pelvis, and/or in the ureters that connect the kidneys to the bladder.

In particular, tumors of the renal calyces, (the outer extensions of the renal pelvis into the parts of the kidneys that do the actual filtering of blood) renal pelvis and ureters originate in the urothelium (also called transitional epithelium), the innermost tissue layer that lines the inner aspect of the bladder, as well as the upper urinary tract. This lining is unique in that it expands and contracts while still providing a barrier to prevent waste products in urine from reentering the bloodstream. But as such, the urothelium is also a target for cancer because the cells are exposed constantly to chemicals and other carcinogens filtered out of the bloodstream and into the urinary tract during the filtering process of the kidney. These carcinogens are capable of stimulating uncontrollable cell division or growth.

Thus, it is not surprising that urothelial cancer is the fifth most common non-skin malignancy in the United States, often occurring after many decades of exposure to a variety of carcinogenic products (e.g., chemicals, radiation or tobacco). It is also not surprising that because the renal calyces, renal pelvis, ureters and bladder share common urothelial cells, the cancers involving these organs often appear and behave similarly. The difference, however, is that because the bladder acts as a reservoir, it may be at greater cancer risk since its urothelial cells are exposed for prolonged periods to potentially harmful substances. Under certain conditions, such as when the urine has an unusually high concentration of carcinogens, cancer may also occur in the kidney or ureters.

Who is at risk for upper urinary tract cancer?

Men are roughly twice as likely to develop these tumors as women but women have a 50 percent higher chance of dying from them. Scientists have yet to pinpoint the role of race in the seriousness of upper tract tumors, but they believe that because of other similarities with bladder cancer, which is far less common, but more deadly in blacks of each gender than white, the differences with upper urinary tract cancer will be the same. As with bladder cancer, the peak incidence for upper tract cancer is in the elderly – it is most common in individuals over the age of 70 with tumors rare in patients younger than age 40. These tumors are highly likely to be multifocal or occur in more than one place.

While the most potent triggers include long-term exposure to a variety of workplace chemicals – manufacturing or refining substances such as dyes, petrochemicals and plastics – from a population wide viewpoint, the worst offender is cigarettes. If you have been a smoker, your risk level is related roughly to the number of years you have used tobacco. Also, unlike lung and esophageal cancer, where the risk of malignancy goes down rapidly within two or three years after smoking is stopped, the risk of upper urinary tract or bladder cancer takes decades to descend. Even then, it never reaches a non-smoker’s level of risk. Other risk factors include ingestion of large quantities of pain medicines include phenacetin and other analgesics for many years or certain herbal preparations used to help lose weight.

What are the symptoms of upper urinary tract cancer?

The principal symptom is hematuria or blood in the urine. Since hematuria can also indicate any number of urinary tract problems, all possible sources of blood should be investigated, beginning with the upper urinary tract.

A second common sign of kidney cancer is a blockage of the kidney and collecting system above the malignancy. You may have no symptoms if this blockage is caused by the tumor itself. In fact, the tumor growth process may be so slow that the malignancy causes no symptoms and is only detected incidentally by an X-ray or ultrasound that reveals abnormal kidney enlargement.  A person may experience severe pain in the lower back, flank or even abdomen along with nausea. Since these are also signs of kidney stones, that person should see a urologist immediately to get an accurate diagnosis.

Other less common presenting complaints include symptoms of advanced disease, including flank or abdominal mass, weight loss, anorexia, and bone pain. 

How is upper urinary tract cancer diagnosed?

Investigating for cancer starts with a complete medical history and physical examination, during which your urologist will feel your abdomen, flank, and back for any lumps or masses. He or she will also order a group of blood tests to check for any chemical changes. Often a microscopic examination (cytology) of shed malignant cells can assist in identifying an upper urinary tract cancer. This can be accomplished by examining urine. The caution, however, is that normal urine from the other kidney may dilute the malignant cells, making the test not adequately sensitive for detecting upper tract cancers.

If your doctor suspects a malignancy or still cannot locate the source of your bleeding, they will probably order various imaging tests, starting with a computerized tomography (CT) scan with pyelography. Use of this test may be limited in patients with poor kidney function.

Today, doctors also rely on other sophisticated imaging technologies, either individually or in combination, to evaluate hematuria and flank pain. Both kidney ultrasound and CT scans are painless, non-invasive ways to scope the organ. But while CT scans can detect kidney and ureteral stones with great sensitivity, they are less capable of diagnosing urinary tract tumors unless they are combined with IVP or intravenous injection of contrast dye. CT scan or MRI may also be helpful in assessing if the cancer has spread to any other organs such as lung, liver, lymph nodes and bones.

If your source of bleeding is still in doubt, your doctor may order a cystoscopy, a telescopic look through the urethra into the bladder, using a special fiber-optic instrument. Combining cystoscopy with a retrograde X-ray using contrast dye injected up the ureters into the kidney may be particularly necessary if you have poor kidney function since excreting contrast dye alone can be inadequate.

If the urologist still does not have a complete picture, he or she may order a direct visual inspection of your upper urinary tract.  A thin scope is inserted through the ureteral opening into the bladder and passed upwards inside the ureter to the renal pelvis. If necessary, the doctor will take a biopsy so a definitive diagnosis can be made.

In any case, once the urologist has a confirmed diagnosis, he or she will determine if and how far the tumor has spread to distant parts of the body by focusing on common sites for metastases. Again, a CT scan may be used to evaluate the abdomen, pelvis and neighboring lymph nodes and organs, such as the liver. But your doctor may also order an MRI, an imaging technique using short magnetic field bursts to create images on a computer. Other possible tests include a chest X-ray to look at your lungs and a bone scan to examine your skeleton to ensure the cancer has not spread to the bones.

How is upper urinary tract cancer treated?

The treatment course chosen by you and your physician will depend on many factors, including how aggressive the tumor is, the size, location and extent of your tumor as well as your age, medical history and overall health. The anatomy of your kidney’s collecting system may also come into play.

The majority of renal pelvis and ureteral cancers are treated with a nephroureterectomy – surgical removal of the kidney and one entire ureter including its insertion into the bladder. The “radical” form of this procedure involves removing the entire kidney and ureter plus surrounding lymph nodes and tissue. Since you will no longer have use of the kidney, your doctor will be concerned about your overall kidney function. If you have already lost a kidney to another malignancy or a non-cancer event – stones, infections or trauma -or if your overall kidney function is impaired from a medical disease such as diabetes, high blood pressure, or glomerulonephritis , your doctor will make an effort to keep the remaining kidney and ureter on the side that is involved with the tumor.

If your doctor opts to spare the kidney the tumor can be removed by either segmental resection or with endoscopic removal. Segmental resection involves removing the affected portion of the urinary tract and then re-attaching the plumbing so that the kidney is still connected to the bladder. Alternatively in selected patients, the tumor can be removed through a small scope called a ureteroscope. This is particularly successful if the growth is small, localized and not very aggressive-looking (low grade) under the microscope.

While topical chemotherapy and immunotherapy often works well in preventing bladder tumor recurrences when instilled into the bladder, it is not commonly administered for renal pelvis or ureteral cancer. Unlike the bladder, which retains fluid for hours, giving any precancerous tissue ample exposure to powerful medicines that could make a difference, the upper urinary tract collecting system is a channel. So drug exposure is far less reliable. Still, your doctor may use drugs in addition to surgery under some circumstances, such as poor or no function in the opposite kidney. Likewise, targeting high-energy radiation or gamma rays at malignant cells has proven very effective in destroying other cancers with minimal damage to normal organs. However, it is rarely used for urothelial tumors since the area is small and there is a risk of toxicity to neighboring tissue, including the remaining kidney tissue.

What can be expected after treatment for upper urinary tract cancer?

The recovery after the procedure depends on the procedure chosen. A minimally invasive approach will render a quicker recovery compared to traditional open surgical approaches. However a minimally invasive approach is not always the best option in all cases. If your surgeon has removed your kidney, but you have a functioning spare, your quality of life, diet and medications should not be seriously affected since one good kidney can nearly do the work of two.

But, as with bladder cancer, recurrences of urothelial tumors elsewhere in the urinary tract are common, even if the initial growth is only superficial. About 30 percent of patients with upper tract urothelial tumors that have been removed subsequently develop new tumors lower in the ureter or the bladder. You will need frequent follow-up cystoscopic examinations of the bladder and remaining upper tract. If the lower ureter on the side of the cancer is not removed, it will be surveyed regularly with either retrograde X-rays or a scope.

Also, cancer recurs in the opposite upper urinary tract in less than 3 to 5 percent of patients with prior upper tract tumors. Although preservation of a kidney is generally desirable, in most cases, you can lose an entire kidney and ureter from treatment without causing undue risk to the other organ or your future health.

The prognosis or outlook for patients with cancers of the upper urinary tract is, in large part, dependent on two factors: 

  1. How aggressive the cancer cells are found to be. Low grade disease is considered less aggressive and has a lower likelihood of spreading to other organs and high grade disease is more aggressive with a higher chance of disease spread outside the bladder. 
  2. How far the malignancy has penetrated into the wall of the collecting system or beyond. Prior to treatment, your doctor will stage your cancer, to determine how far it has spread. Often these factors cannot be determined accurately until the tumor is removed and studied microscopically by a pathologist . When an upper urinary tract cancer is caught early, the chances of surgical cure are good.

Frequently Asked Questions:

Will I need additional treatment after the tumor is removed?

You will need continued check-ups of your lower and upper urinary tracts. Upper urinary tract TCC is more likely to occur in multiple places compared to other cancers. For the first few years after treatment and less frequently thereafter, your doctor will perform quarterly cystoscopic and other examinations. Those follow ups should continue at least annually throughout your lifetime. Additional therapy for a removed tumor will depend, in large part, on the extent or spread of the malignancy . If it is confined to the ureter or renal pelvis without involving neighboring lymph nodes or the tissues outside the collection system, there is a high likelihood of cure. Additional treatments would not be necessary. But if the cancer has spread well beyond the collecting system, especially involving regional lymph nodes, you will probably be placed on additional systemic chemotherapy to combat any microscopic tumor deposits that may be present already but not apparent.

If my kidney is removed will I need dialysis?

Rarely would you need dialysis unless you have a serious pre-existing kidney dysfunction or major abnormalities (including absence) of your other kidney.

Are my relatives at increased risk for this cancer if I have it?

Unlike cancers of the prostate and certain forms of kidney, breast and colon cancer, there is little evidence that urothelial cancer is inherited. But in a very small proportion of cases there are clear-cut genetic tendencies that probably impact how someone’s body might handle or metabolize a specific chemical carcinogen . It is possible in those circumstances that a close relative with identical exposures to the same cancer-causing agent would be at higher risk for upper tract cancers than unrelated individuals with similar exposures. So if you have kidney or bladder cancer, it is probably beneficial to your parents, siblings or children to avoid obvious carcinogens. Moreover, anyone, particularly someone in that intimate circle who develops signs of urothelial cancer, should see a urologist immediately.

After surgery, how can I protect my remaining kidney?

If your surgery leaves you with only one kidney, it is important to avoid major contact sports (e.g., football, karate or boxing) that could hurt your organ. It is also smart to avoid routine use of non-steroidal anti-inflammatory drugs (e.g., aspirin and ibuprofen). In rare instances, they can cause kidney damage. Also, by treating medical conditions – high blood pressure, diabetes , high cholesterol and obesity – that have the potential of causing kidney deterioration, you are preventing future damage. Depending on how well your remaining kidney functions, it may be necessary to avoid intravenous iodine contrast dyes used for certain imaging tests and X-rays. A diet with limited salt and protein ingestion may be beneficial for those with compromised kidney function.

Are there known ways to prevent upper urinary tract cancers?

Since the exact cause of urothelial cancer is not known, it is impossible to prevent every case. Still, scientists have identified a strong association between renal pelvis and ureteral cancers and tobacco use. So for the vast majority of individuals, avoiding cigarettes is a most important first step. Others include eluding or being careful with cancer-causing agents such as chemicals in the workplace. A sobering word to the wise – the risks for urothelial cancer only slowly decline over many years after one stops smoking. In addition, the risk for more aggressive urothelial cancers is much higher in smokers who have already had their first urothelial cancer treated successfully. Also, while data are inconclusive on urothelial cancer risks tied to pipes, cigars or chewing tobacco, they are believed to be far lower than those linked to cigarettes.

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