Kidney Cancer: The Basics

Ryan P. Smith, MD and Christine Hill-Kayser, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 25, 2008

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What is the Kidney?

The kidneys are two bean-shaped organs that are located in the back of the abdomen, and that have many important functions essential for life. Among the most important are filtrating the blood, removing waste products from the blood and ensuring that the electrolytes within the blood are correctly balanced. In addition, the kidneys produce erythropoietin, a hormone responsible for the production of (the oxygen carrying) red blood cells. Each of the kidneys can be divided into two main functional parts. The outer region of the kidney is called the cortex The cortex consists of a series of tubes (called collecting tubules) and is responsible for the filtration of blood.. The inner region of the kidney is called the renal pelvis. The renal pelvis contains medullary pyramids that collect the filtrate (urine) from collecting tubules in the cortex and send it through the ureters to the urinary bladder. Different types of cancers develop from the two different regions of the kidneys.

The kidneys are located in the posterior aspect of the abdomen, directly in front of where the lowest ribs can be felt on a person's back. A physician can palpate them in the abdomen at times, though often only if the kidney is enlarged or has a mass on it.

What is kidney cancer?

The definition of a tumor is a mass of abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any ability to spread to distant parts of the body. A tumor is called malignant, or cancer, if tumor cells gain the propensity to invade tissues and spread locally as well as to distant parts of the body. In this sense, kidney cancer occurs when cells in either the cortex of the kidney or cells in the renal pelvis grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Cancers are described by the types of cells from which they arise. Again, when discussing kidney cancer, the cortex and the renal pelvis must be discussed separately. In the kidney cortex, the vast majority of cancers arise from the cells that line the collecting tubules, more specifically, the proximal tubules. Cancers that develop from lining such as this are called carcinomas. In this case, they are called renal cell carcinomas. Over 75% of renal cell carcinomas are called clear cell carcinomas, named after the characteristics they display when looking at them under the microscope. Other classifications, in decreasing order of prevalence, include chromophilic, chromophobic, oncocytic, and collecting duct cancers. However, it does not appear that these various types of renal cell carcinoma differ in presentation or prognosis.

Cancers of the renal pelvis, or medulla, are uncommon. Over 90% of cancers that develop in the renal pelvis are called transitional cell carcinomas. They are so named because they develop from cells that line the renal pelvis and upper ureters.

Am I at risk for kidney cancer?

Kidney cancer occurs in approximately 31,000 Americans per year and cancers of the renal pelvis will occur in approximately 3,000 Americans per year. Most patients are diagnosed between the ages of 50 and 70. Kidney cancer is more common in men than women, with an equal preponderance in whites and blacks. A number of risk factors are associated with an increased probability of renal cell cancer: The most prominent risk is cigarette smoking. Persons who smoke have twice the risk of developing kidney cancer as people who don’t smoke, and smoking is directly responsible for up to one out of every three cancers. The risk for kidney cancer also increases fourfold in persons with a first-degree relative who had kidney cancer. Other, less-proven risk factors include obesity (especially in women), analgesic abuse, high blood pressure, and several uncommon hereditary diseases, including von Hippel-Lindau disease and polycystic kidney disease.

How can I prevent kidney cancer?

As cigarette smoking doubles the risk of kidney cancer, the best way to decrease your risk of developing kidney cancer is to discontinue smoking. Other than smoking, the only substantial risk factors for the development of kidney cancer are related to family history. Obviously, no one can change the family they are born into, so the risk factor of having someone in the family with a history of kidney cancer, or rare genetic diseases such as von Hippel Lindau and polycystic disease cannot be prevented.

What screening tests are available?

There are no screening tests for kidney cancer that are akin to mammography for breast cancer or colonoscopy for colorectal cancer. However, the use of CT scans and ultrasounds have enhanced the early detection of kidney cancer once signs or symptoms have developed (see below). Intravenous pyelograms (IVP) are used to assess kidney function. IVPs are done by injecting dye into a patient's arm and then taking x-rays of the abdomen to see that dye subsequently excreted by the kidneys as urine. Cytology is simply looking at urine under a microscope and looking for cancerous cells within the urine. Because they may cause early symptoms that lead to testing, kidney cancers that develop in the area of the collecting system may be detected earlier than those in other regions.

With the advent of CT scans and ultrasounds, 25-40% of kidney cancers are now detected incidentally during the work up of a different problem. These tumors are more likely to be smaller (hence causing no symptoms), and hence more likely to result in a cure.

What are signs of kidney cancer?

Kidney cancer presents as signs and symptoms of either the local tumor in the kidney or as signs and symptoms resulting from spread of disease to other locations in the body (metastatic disease). Symptoms resulting from local tumor extension include hematuria (blood in the urine), abdominal pain, and a flank mass. Hematuria is the most common symptom and present as either gross hematuria, where the blood is visible in the urine, or as microscopic hematuria, where the blood is only detected by laboratory testing. Therefore, any presence of blood in the urine that is detected in a urine sample should be investigated. In medical textbooks, patients present with the "classic triad" of all three symptoms, though only about 10% of patients actually have all three symptoms at diagnosis.

Symptoms caused by metastatic disease include fever, weight loss, and night sweats (drenching sweats that require changing of clothes or bedsheets). Other symptoms include hypertension, increased calcium in the blood, and liver problems. These more unique symptoms are thought to be caused by chemical signals released by the tumor cells into the bloodstream and the body's reaction to them.

How is kidney cancer diagnosed and staged?

Diagnosis

Work up of a kidney cancer usually starts after the patient develops symptoms, with the exception of those cancers that are found incidentally. The point of all of the tests done prior to treatment of kidney cancer is to determine the extent of disease that is present so that treatment can be adjusted accordingly. This includes documenting the extent of disease both locally, in the tissues and lymph nodes surrounding the kidney, as well as ensuring there is no spread distantly, outside the area of the kidney (called metastases). The most sensitive test to document local disease is the CT scan, which has been shown to predict the tumor extent 90% of patients. MRI scans have been used to ensure the tumor has not involved any of the large blood vessels that are in the vicinity of the kidney. Other tests, including basic laboratory blood tests and analysis of the urinemay be used to evaluate general health and the extend of the cancer. In addition, chest x-ray and bone scan are usually done, to ensure that metastatic spread to the lungs and bones, respectively, has not occurred. To obtain a diagnosis of any cancer, tissue or cells must be examined by a pathologist. Therefore, to obtain a diagnosis of kidney cancer, a biopsy is often obtained by inserting a needle into the presumed tumor mass during a CT scan. However, there are also times that the CT scan and/or MRI is so convincing that the mass is a tumor, that the initial biopsy is done during an open surgical procedure, which is done to ultimately remove the kidney as treatment for the kidney cancer. The most appropriate surgical approach must be determined on an individual basis.

Staging

After all of these tests are performed, the stage of the cancer is known. The staging of a cancer basically describes how much it has grown before the diagnosis has been made, documenting the extent of disease. This is often extremely important in terms of what treatment is offered to each individual patient. Before the staging systems are introduced, we will first describe some of the ways that cancers may grow and spread.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way kidney cancer can spread is by local extension to invade through the normal structures. This initially includes the kidney, hence causing hematuria, a mass, and abdominal pain. If more growth occurs, cancer can grow to involve the main vein that leaves the kidney (the renal vein), the large vein that returns blood from the bottom half of the body to the heart (the inferior vena cava), or into other organs-most commonly the adrenal glands which sit atop the kidneys.

Kidney cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Kidney cancer can spread, at times, into the lymph nodes surrounding the kidney, called the perirenal lymph nodes.

Kidney cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and cause distant metastases. Cancers of the kidney generally spread locally into the fat surrounding the kidney, the adrenal glands, or the veins prior to spreading via the lymphatic system or the bloodstream. However, tumors, especially larger tumors, can access the bloodstream and spread to the lungs and bones, most commonly. Kidney tumors have also been known to spread to the testis and ovaries through the testicular or ovarian veins that are in close proximity to the kidney.

The staging system used today in kidney cancer is designed to describe the extent of disease within the area of the kidney, in the surrounding lymph nodes, and distantly. The staging system most commonly used today to describe kidney tumors is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the extent of the "primary" tumor (the tumor in the kidney itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (i.e.-metastases).

The "T" stage is as follows:

For kidney (cortex) tumors:

  • T1-tumor size of 7 cm or less and confined to the kidney
  • T2-tumor size more than 7 cm, but still confined to the kidney
  • T3a-tumor invading into the adrenal gland or just outside of the kidney
  • T3b-tumor invading into the renal vein or inferior vena cava, but contained below the diaphragm
  • T3c- tumor invading into the renal vein or inferior vena cava, and extending above the diaphragm
  • T4-tumor invades outside of these areas

For medullary tumors:

  • T1-tumor contained within the collecting system
  • T2-tumor invades into the muscular layer of the wall of the collecting system
  • T3-tumor invades into the fat surrounding the collecting system
  • T4-tumor invades into other organs

The "N" stage is as follows for any subsite:

  • N0-no spread to lymph nodes
  • N1-tumor spread to a single lymph node
  • N2-tumor spread to multiple lymph nodes or for collecting system tumors, lymph node spread that is between 2 and 5 cm
  • N3-for collecting system tumors only, those lymph nodes that are >5 cm

The "M" stage is as follows:

  • M0-no tumor spread to other organs
  • M1-tumor spread to other organs

The overall stage is based on a combination of these T, N, and M parameters:

For kidney cortex tumors

  • Stage I: T1N0M0
  • Stage II: T2N0M0
  • Stage III:
    • T1-2N1M0
    • T3N0-1M0
  • Stage IV: and T4, any N2 or M1

For collecting system tumors

  • Stage I: T1N0M0
  • Stage II: T2N0M0
  • Stage III: T3N0M0
  • Stage IV: any T4, any N1-3, any M1

Though complicated, these staging systems help physicians determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer.

What are the treatments for kidney cancer?

Surgical resection (removal) is the only known curative treatment for kidney cancer. The procedure that is most often done in the case of kidney cancer is called a nephrectomy. This procedure includes the removal of the entire kidney that is involved with tumor The surgical procedure also usually includes removing at least some of the lymph nodes surrounding the kidney, which has shown to increase survival in patients with kidney cancer. So-called partial nephrectomies (where only a part of the kidney is removed) may be utilized in some patients with small tumors. This should only be attempted in patients with tumors <4cm. If the tumor can be completely removed, the risk of the tumor coming back in the remaining part of the kidney is about 5%. Therefore, this treatment is very effective.

For larger tumors that require total nephrectomy, the adrenal gland and the fat surrounding the kidney and adrenal gland may need to be removed in order for the entire tumor to be removed.

Even if the kidney cancer has spread to a single different part of the body, a nephrectomy may be recommended, as it has been shown to improve survival. If there are many sites of disease, however, nephrectomy has not been shown to be useful.

Radiation therapy makes the use of high energy x-rays to kill cancer cells. It does this by damaging the DNA in tumor cells. Normal cells in our bodies can repair radiation damage much more quickly than tumor cells can, so while tumor cells are killed by radiation, many normal cells are not. This is the basis for the use of radiation therapy in cancer treatment. Radiation is delivered using large machines that produce the high energy x-rays. Radiation therapy, however, is not routinely used in the initial treatment of kidney cancer.. Radiation may be considered for patients whose tumors are too large to be completely removed; after as much surgical removal as possible is performed, radiation may be useful in treating tumor that remains. This treatment is experimental and should be done only as part of a clinical trial.

Radiation may also be used as a method for pain relief in patients who have pain from kidney cancer that has spread to other regions of the body.

Chemotherapies are drugs that are used to kill tumor cells. Up to this point, there is no chemotherapy regimen that has been consistently shown to be efficacious in the treatment of curative or metastatic kidney cancer. New modalities are constantly being investigated, including interferon, anti-angiogenesis agents (which inhibit the tumor from growing more blood vessels), and molecular agents that target specific genes that may be essential for the tumor cells' survivals.



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