a. Von-Hippel Lindau disease is a syndrome with multiple cysts in the kidney and blood vessel malformations in the brain. The kidney tumors are usually benign but may become malignant, and start in both kidneys.
b. Chromosome #3 abnormalities are associated with malformed kidneys and occasional kidney cancers.
c. Beckwith-Wiedemann and Drash syndromes have abnomalities at chromosome #11 and are linked to childhood kidney cancer, called "Wilm's Tumor". The managment of Wilm's Tumor is different than for adult cancers. 5) Hormonal Factors-- giving large amounts of the female hormone estrogen for prostate cancers in men has been linked to the development of kidney cancer. If DES, a potent estrogen, is given to hampsters, they get kidney cancers. Hormones can also be used to treat kidney cancers, as will be seen.

What are the Symptoms of Kidney Cancer?

Often kidney cancer has no symptoms, and is found incidently on an imaging scan of the abdomen, or never discovered at all. The smaller the tumor, the less chance it will cause problems and spread to other areas. However, tumors larger than 3 cm. are more likely to be cancerous and continue to grow, eventually causing problems, The most common symptoms of kidney cancer are:

1) Blood in the Urine ("Hematuria") can be a sign of cancer anywhere along the urinary tract. However, most times blood in the urine is caused by kidney stones, infection, or trauma rather than cancer.
2) Flank Pain from the tumor stretching the "capsule" that surrounds the kidney.
3) Flank Mass from the growing tumor. When combined with flank pain and blood in the urine, these three things are called the "classic triad" for kidney cancers. However, only 10% of the patients with kidney cancer have all three symptoms of this "classic triad"!
4) High Blood Pressure can be seen with anything that alters the kidney's shape.
5) Cancer Syndromes ("paraneoplastic syndromes") from chemicals or hormones produced by the cancer itself and released into the bloodstream. Such syndromes include high blood calcium leading to extreme fatigue, and liver failure ("Staufer Syndrome") which is found in up to 40% of patients with renal cell cancer. This leads to a swollen liver, poor blood clotting ability, and is of cancer spread.
6) Signs of Spread include weight loss, fevers, and night sweats. Symptoms may be found in the bones, lungs or liver (pain) or brain (motor and sensory changes) from spread to these organs.

How Does Kidney Cancer Spread?

It starts in a single cell, usually from the lining of the small tubes ("renal tubules") in the kidney. It grows locally, pushing into the fat surrounding the kidney and evenually through the tough Gerota's Facia.It can travel through the lymphatic system around the kidney to local lymph nodes, and eventually to distant ones along the aorta. Cancer cells may break off, travel through the bloodstream, and "seed" to the liver, lungs, bone and brain. Most patients who's lymph nodes are involved will ultimately develop blood-born spread to distant organs, and even some patients who's lymph nodes are not involved can get distant spread. Nonetheless, lymph nodes remain an indicator for how advanced the disease is, as will be seen under "staging" below. In general, the larger the tumor, the greater it's likelihood of having spread. About 10% of tumors measuring less than 6cm. (under 3 inches) have distant spread at diagnosis, while tumors less than 3cm. have less than a 2% chance of distant spread when first discovered.

How is Kidney Cancer Diagnosed and Evaluated?

The only way to be absolutely sure of a diagnosis of kidney cancer is to get a piece of the tumor and have it evaluated by a pathologist (a physician who specializes in making diagnosis from tissue samples). If a patient comes to the doctor with symptoms suggestive of a cancer in the urinary system, the following tests are. normally done:

1) Complete Physical Examination especially looking for high blood pressure, abdominal masses, and signs of anemia or liver failure.
2) Blood Tests include routine Complete Blood Count (CBC) to test for anemia and infection, and a Chemistry Panel (SMA) which tells about kidney and liver function, as well as blood sugar and sodium and potassium levels. Kidney failure leading to uremia is shown by elevated blood "creatinine" (over 2.0) and "blood urea nitrogen" (BUN) over 40.
3) Urine Tests include complete urinalysis to look for blood, signs of infection, or protien being spilled into the urine which indicates kidney damage.
4) Imaging Tests include "Intravenous Pyelogram" (IVP) which is done when unexplained blood is found in the urine. For this test, a minute amount of contrast dye is injected into an arm vein and this dye is excreted by the kidneys, and ultimately urinated out. X-ray pictures are taken of the abdomen and pelvis to track this dye as its excreted, and abnormalities (like stones or tumor) in the urinary tract can then be identified. The next most common test is a CAT scan of the the abdomen which is excellent for looking at the shape of the kidneys. A tumor larger than 1/2 inch can be seen with the CAT scan, which is also helping for looking for spread of the tumor to the adrenals, lymph glands, or liver. Other tests than can "look" at the kidneys are Magnetic Resonance Imaging (MRI) which uses magnetism instead of radiation to view the softer tissue of the body in incredible detail, or Ultrasound which uses sound waves to look for tumors or cyts on the kidneys. All patients will get plain Chest X-ray to look for signs of spread to the lungs. When surgery is contemplated, some surgeons like getting an "angiogram" of the kidneys which images the blood vessels running through them, since the shape of the blood vessels will approximate the shape of the tumor and tell about its blood supply. Special tests like bone scans (to look for cancer spread to bones) or head CAT scans (to look for spread to the brain) are only done if there are actual symptoms in these areas.
5) Surgical Diagnosis includes either doing a "biopsy" (taking a small piece of the tumor) or doing an "open procedure" (operation) to remove the tumor and then analyze it. A biopsy is often done with using local anesthesia with a "fine needle" placed through the skin and muscle, into the kidney. This placement is usually done under CT scan guidance. It is about 85% accurate at diagnosing cancer. If the tumor is causing symptoms, and the patient can be operated upon, then the diagnosis can be made at surgery. The specifics of surgery are described in the "treatment" section below.

Many tumors smaller than 3cm. are not cancer, but benign tumors instead. Although larger tumors (over 6cm.) are more likely to be cancerous, not all of them are, with studies showing about 60% of them are actually cancer. Thus it is important to actually have a "tissue diagnosis", by biopsy or surgery, before concluding that a tumor is cancerous. If the cancer has obviously spread to other areas, it may be easier to biopsy those areas than the "primary" tumor within the kidney to make the diagnosis.

What are the Types of Kidney Cancer?

Renal Cell Carcinoma, a form of "adenocarcinoma" that arises from glands, is over 98% of adult kidney cancers. It is also called "hypernephroma" or "Grawitz tumor" and often abbreviated "RCC". Less common cancers of the kidney include lymphomas (from the immune cells in the kidney) and sarcomas, which arise from fat or muscle. In children, Wilm's tumor is the most common type, but its diagnosis and treatment is a different subject than adult kidney cancers.

How is the Extent of Kidney Cancer Gauged?

Like all Cancers, the extent of kidney cancer is given by the "Stage". The stage considers the size of the tumor, to where it has locally grown, and to where it has spread:

"Stage I" means the cancer is smaller than 2.5 cm. and limited to the kidney
"Stage II" means the cancer is larger than 2.5 cm. and limited to the kidney
"Stage III" means the cancer spread into the adrenal gland or outside the kidney, but not past "Gerota's
"Stage IV" means the cancer invades through Gerota's Facia, or has otherwise spread to more distant lymph nodes or other areas of the body.

What is Survival from Kidney Cancer?

This naturally depends upon the stage of disease and treatment selected. In general, conventional treatment has yielded the following results by stage:

What is the Conventional Treatment for Kidney Cancer?

Surgery has been, and remains, the conventional treatment for renal cell carcinoma. It is the only proven curative therapy. Great advancements have been made in surgical techniques over the past 3 decades, and surgery is more effective and safer than ever before. The actual surgery is performed by a "urologist" Many operable tumors are incidently discovered during a workup for some other condition, and for these patients 5 - year survival exceeds 90%. For those with less favorable cancers, surgery continues to offer the best hope for cure.

The specifics of surgery include a throrough pre-operative evaluation to determine that the tumor is still localized to the kidney area - since if it has already spread to other body areas surgery is probably useless. There is no increase in survival documented for "debulking" surgery - that is just reducing the size of the cancer, but not removing it all. It is also necessary to determine that the patient is medically operable- meaning that they are an "acceptable" anesthesia risk and can tolerate the operation. High blood pressure which is uncontrolled, poor breathing ability (say from emphysema) or recent heart attack may disqualify the patient from getting surgery. If surgery can be performed, the patient is placed under general anesthesia and an incision is made into their flank on the side of the cancer, below the ribcage. The cancer is exposed, and commonly the entire kidney and adrenal are removed after clamping off their supplying blood vessels. If the cancer has spread locally, it is meticulously dissected off other organs it has invaded and samples of tissue (called "frozen sections") are sent during the operation to a pathologist who is standing by to analyze them. The idea is to get "clear margins", meaning that the tumor has been completely removed from all its peripheral areas. Lymph glands are often removed to test whether the cancer has spread to them, and certainly any enlarged lymph glands (> 1 cm.) are removed. The larger the lymph nodes, the more suspicious they are for cancer spread.

The extensiveness of the surgery performed has been found to be important for predicting results. If just the affected kidney is removed ("total nephrectomy") the results have been poorer than if the entire contents of "Gerota's Facia" are removed ("radical nephrectomy"). The more radical operation will include removal of the adrenal gland, fat surrounding the kidney, and the facia itself. The lymph nodes in the vicinity are also commonly removed. Although removing lymph nodes doesn't seen to affect survival (since patients with cancer spread to lymph nodes often have it spread to distant body areas) it gives important staging information for the urologist, and may help direct further treatment. Any treatment after surgery is called "adjuvant" or extra therapy, and is described below. After the operation, the layers of abdominal facia, muscle and skin are sutured separately, and the patient is sent to the post-surgical suite for observation. If problems develop, they are sent to intensive care, while if everything is normal they are sent to a regular hospital room. It is common today to hook up a morphine or demerol pump for pain after surgery. This pump is controlled by the patient via pushing a button, and is called "patient contolled analgesia' or 'PCA' for short. It is a great advance in adding to patient comfort. After bowel sounds return (usually 2 days after surgery) the patient is started on a liquid diet, which is advanced to regular food as tolerated. The patient is usually in the hospital about 4 days until discharge to home.

Surgery is generally much safer than it used to be. The standard risks of surgery are a chance of operative death (2%) and development of infection (10%). There is a risk of urine leakage or urine cyst formation ("urocele") from where the ureter is tied off from the bladder. There is about a 5% risk of suture rupture, which can lead to the bladder bursting out through the abdominal wall. A significant risk is kidney failure in the other "healthy" kidney, especially if that kidney wasn't so healthy to begin with or if the surgery was longer than expected. If that kindey's blood supply is threatened by lowered blood pressure from surgery, the kidney may develop "acute tubular necrosis" or "ATN" for short. This means that its urine production system is damaged, so it doesn't produce urine and the patient will need to get dialysis. Fortunately, it is often temporary and that remaining kidney will heal in time and produce urine. Obviously, the production of urine is carefully monitored, along with blood chemistries and blood counts, after nephrectomy. The risk of short term kidney failure is about IO%, but of long term term failure is only about 3%. Possible longer term side-effects of surgery include risk of bowel or urine flow obstruction from adhesive bands of scar tissue forming after surgery (about 5%) which will require a second surgery to relieve the obstruction, development of a lymph fluid collection in the removed kidney bed (called a "lymphocele") or abcess which must be surgically drained. The patient can normally return to light activities within 2 weeks of surgery, and heavy lifting within 6 weeks of surgery. If the remaining kidney works properly, it will have no difficulty in properly purifying the patients whole blood supply- we can do fine on one kidney!

Radiation Therapy has been used either in conjunction with surgery (ie. before or after), or as the sole treatment for renal cell carcinoma. It is prescribed and monitored by a "radiation oncologist" While there is no current proof in the literature that radiation therapy helps survival, it can reduce local regrowth of the cancer. Kidney cancer cells can be killed by radiation, and the benefit of radiation given for metastatic disease symptoms (like bone pain or spread to brain) is well documented and standard treatment. Unfortunately, the amount of radiation that can be safely given to the kidney area itself is limited by the tolerance of the nearby intestines and spinal cord. However, radiation therapy has been used in the past, and is currently recommended for consideration after surgery (as "adjuvant therapy") by many radiation oncologists. The situations after surgery ("post-operative adjuvant radiotherapy") for which it can be recommended are the following:

a) Incomplete tumor removal - residual tumor left in the kidney bed. b) Involvement of local lymph nodes c) Involvement of surrounding renal fat or Gerota's Facia d) Tumor extention up into the great blood vessels e) Spillage of the tumor during surgery The specifics of radiation therapy are going to meet the radiation oncologist, who evaluates the patient and makes a recommendation regarding treatment. If radiation is to be administered, the patient returns to the department for a "simulation" whereby the area to be treated is marked out on a replica treatment machine. The simulation takes about an hour, and X-rays are taken and compared with the patients prior CAT scan to confirm the treatment area, or "portal". Watercolor marks, and eventually small permanent tattoos, are placed on the patients skin to designate the treatment area. The simulation information is fed into a "treatment planning computer", which generates a "Plan". The plan tells how much radiation is going to the tumor area, and how much to surrounding normal tissues. Special lead blocks (which fit into the treatment machine) are usually cut, so the patient returns a day or so later to begin the actual treatment. They are placed in a special room, on a hard table, and aligned with laser lights by the technologist who gives the actual treatment. Treatment is given with an invisible beam of photons, the machine is called a "Linear Accelerator" or "Linac" (sometimes cobalt-60 is used, but this is less common today). The treatment is given Monday through Friday, for 4 to 6 weeks, and takes only several minutes each day. The usual dose given for adjuvant treatment is about 45 Gray (units of radiation), given at a rate of 2 Gray per treatment day.

Radiation is generally easy to recieve; the actual treatments are painless. The patient does not become radioactive, get "radiation poisoning", or lose their scalp hair. Expected side effects of radiation are divided into "acute" and "late" reactions. "Acute" reactions occur during the treatment period, while "late" reactions may occur months to years later. Acute reactions include some skin reddening, and possible diarrhea and urinary frequency. These acute reactions usually quickly resolve after completion of treatment. Later reactions include possible bowel or urinary obstruction from scarring caused by the radiation, especially if surgery was priorly performed. The risk for this is as high as 10% over many years. Also, spinal cord damage leading to tingling or even paralysis may occur, but this is exceedingly rare with proper radiation techniques (less than I%). Also rare but possible is the development of a second tumor caused by the radiation. In general, radiation is a safe treatment, and techniques of administering it have advanced dramatically in the past 3 decades. Although it is not proven to improve survival in renal cell carcinoma, getting local control of the tumor, which is more likely with radiation treatments, is essential for cure.

Chemotherapy is also not proven to increase survival for renal cell carcinoma after surgery, but it has been tried. The rationale for giving chemotherapy is that it is the only treatment which may help kill tumor cells that have broken off the main cancer and then seeded in other body areas. These "micrometastasis" are too small to see with any scan, yet they can grow into large tumors and kill the patient. Both surgery and radiation are only local therapies, whereas chemotherapy is a "systemic" treatment which goes all over the body. While chemotherapy is of proven benefit in some kidney tumors (Wilm's tumor, lymphoma, and transitional cell cancer of the renal pelvis) no current agent is more than 20% effective at getting a response in renal cell carcinoma. Unfortunately, even these responses are short-lived and usually only last about 6 months. Cancer cells can develop resistance to chemotherapy much as bacteria become resistant to antibiotics. The-most effective agents for renal cell carcinoma are vinblastine and 5-Flurouracil. As chemotherapy is ineffective and toxic, it isn't often recommended.

What is the Latest, Effective Treatment for Kidney Cancer?

For small kidney cancers, improvements in surgical technique often allow "nephron sparing surgery". This means that instead of removing the entire kidney, enough of that kidney is left to still perform its functions. This is especially important if both kidneys have small tumors, as can occur from polycystic kidney disease, since it will eliminate the need for dialysis or kidney transplantation. The survival at 5 years is over 90% when small cancers are conservatively removed, along with a "safety margin" of normal tissue. For cancers need the top of the kidney, it is advisable to remove the adrenal gland also. Nephron-sparing surgury is gradually becoming an accepted method of treatment for patients with cancers less than 3 cm. in diameter, so long as they are not in the center of the kidney. Recall that there is no advantage to radiation or chemotherapy for small kidney cancers.

For larger cancers, aggressive surgery is warranted since even patients with cancer extending into the vena cava (major vein) may be cured. Even if the cancer tracks all the way into the heart, successful attempts may be made to cure it. For those who's disease is this extensive, cardiopulmonary bypass must be done at surgery (to shut down the heart for a while to operate upon it). Surgery can also be useful for patients with small, discrete metastatic disease. If there is only one site of distant spread, and it can be surgically removed, 5 year survival is about 30%. The most favorable metastasis to remove is solitary spread to the lung, but excision from other sites (central nervous system or bone) can lead to long term survival, especially if no lymphatic involvement is found.

Removal of the kidney (nephrectomy) used to be advocated even for patients with widespread metastatic disease, since rare but definite resolution of all disease was occasionally seen (1 %). Unfortunately, the remissions were short-lived, and the danger of surgery far exceeded its survival benefit, so this has been abandoned except for relief of symptoms from the tumor itself. Radiation can also be used for this, and more safety.

lmmunotherapy is the latest exciting advancement for patients with advanced kidney cancer. lnterieukin-2 ("IL-2") when given in high doses gives a 20% response, produces long remissions, and cures some patients. Unfortunately high dose IL-2 may have severe side effects, usually chills, fever, headache, or heart attack, or kidney failure (sometimes even fatal). However, combining lower dose IL-2 with another immunotherapy drug, "Alpha-interferon" gives better results (26% response) with much less side effects. Just giving alpha-interferon alone gives a 20% response rate but doesn't help survival. A typical dose for IL-2 is 8 million Units given 4 days a week for 4 weeks by intravenous drip. It was approved by the FDA in 1992 for metastatic kidney cancer, and sometimes produces dramatic results with complete disappearance of the cancer. Combining IL-2, Alpha-interferon, Mitomycin-C and 5-Fluorouracil gives 45% response (the best ever) at UCLA in California. Another new area of research is LAK cell (lymphoctye activated killer) cells made by cultivating white blood cells in IL-2, which are then infused into the patient. The response rate is as high as 33%, but not significantly higher than IL-2 alone. However, more patients have durable remmision, and perhaps cure, with LAK therapy.

The most exciting area of immunotherapy is using Tumor-infiltrating Lymphocyte Cellular Therapy ("TIL"). This is a special white blood cell, the "T-lymphocyte" which are isolated from the cancer itself, usually after radical nephrectomy. They are then stimulated by bathing them in IL-2, where they multiply and increase activity. When put back into the patient, they home in on cancer cells without harming normal cells. UCLA has documented an average response rate of 40% with modifications of "TIL" therapy for patients with metastatic disease, with many patients having prolonged survival.

Thus there is more hope than ever before for those with kidney cancer. For patients with small, localized disease, survival is over 80%, and for those with locally advanced disease over 40%. Cures are now being reported even for patients with distant disease spread with new immunotherapy. CancerAnswers has an In Depth Transcript oon Immunotherapy available through our web site. A patient should take a combination approach for the best chance at cure. The kidney cancer patient should embark on a program of nutritional therapy, exercise, spirituality, and "mind over cancer." Positive mental attitude has clearly been shown to be correlated with better outcomes for cancer patients. Furthermore, a patient should select an alternative therapy that does not interfere with their other therapy and that they can believe in. CancerAnswers offers an Alternative Therapy Transcript on Kidney Cancer available through our Website.

Those individuals that are more at risk for kidney cancer would benefit from getting serious medical advice from a physician. Those mysterious symptoms may be a sign of something very serious, such as cancer.

This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Kidney Cancer. Much more, including latest additional treatments for Kidney Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.