Kidney Cancer

What is the Kidney?
The kidneys are two bean-shaped organs 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 correct. In addition, the kidneys produce erythropoetin, a hormone responsible for the production of (the oxygen carrying) red blood cells. The kidneys can be divided into two main functional parts. The outer region of the kidneys is called the cortex, and, as it is responsible for the filtration of blood, it consists of series of collecting tubules. The inner region of the kidneys contain medullary pyramids that collect the filtrate (urine) from these collecting tubules and send it to the urinary bladder via the ureters. This inner region is called the renal pelvis. Different types of cancers develop from the two different regions of the kidneys.
The kidneys are located in the posterior aspect of the abdomen, basically 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 quickly and 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 spread. A malignant tumor is called cancer when these 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 mentioned 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 obviously 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. It 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, though the most prominent risk is cigarette smoking. Persons who smoke have twice the risk of developing kidney cancer, 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 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 pedigree. 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 screening tests for kidney cancer that are akin to mammography or colonoscopy. However, the use of CT scans and ultrasounds have enhanced the early detection of kidney cancer once signs or symptoms have developed (see below). Kidney cancers that develop in the area of the collecting system (the inner portion of the kidney) are prone to earlier detection because of intravenous pyelograms (IVPs) and urine cytology. 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.
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% 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.
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.
How is kidney cancer diagnosed and staged?
Diagnosis
Work up of a kidney cancer usually starts after the patient presents with symptoms, with the exception of those cancers that are found incidentally. The entire 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 preoperatively in 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 urine. In addition, a chest x-ray and bone scan are usually done, to ensure against metastatic spread to the lungs and bones, respectively. In the case of cancers within the inner part of the kidney (the collecting system), the IVP is an additional test that is extremely important to not only document the local extent of tumor, but also to ensure against simultaneous tumors somewhere else in the urine collecting system
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. This, obviously, 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 is 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, first some background on how cancers grow and spread, and therefore advance in stage.
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 giving the symptoms of hematuria, a mass and abdominal pain. If more growth occurs, it could 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.
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 the tumors that arise from cells' travel to other organs are called 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. This replaced the "Robson Modification of the Flocks and Kadesky Staging System" because of its superiority in describing the local extent and lymph node involvement. 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 esophagus 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, but extending above the diaphragm
T4-tumor invades outside of these areas
For collecting system 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 possible curative treatment for kidney cancer. The procedure that is done in the case of kidney cancer is called a radical nephrectomy. This procedure includes the removal of the entire kidney that is involved with tumor as well as the adrenal gland associated with the kidney and subsequently, the fat surrounding the kidney and adrenal gland. 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) has been attempted 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 region of the kidney is about 5%. Therefore, this treatment is very effective.
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 body can repair radiation damage much quicker than tumor cells, 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. As the local failure in patients with complete removal of the tumor is 5%, adding local radiation, which is done to improve local control of a tumor, would do little to improve results. In patients without a complete removal of tumor, there could be a role for postoperative radiation therapy, though it should only be done as part of an investigational trial.
Chemotherapy is defined as 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.