Surgery

It takes time to heal after surgery, and the time needed to recover is different for each person. Patients are often uncomfortable during the first few days. However, medicine can usually control their pain. Before surgery, patients should discuss the plan for pain relief with the doctor or nurse. After surgery, the doctor can adjust the plan if more pain relief is needed

It is common to feel tired or weak for a while. The health care team watches the patient for signs of kidney problems by monitoring the amount of fluid the patient takes in and the amount of urine produced. They also watch for signs of bleeding, infection, or other problems requiring immediate treatment. Lab tests help the health care team monitor for signs of problems.

If one kidney is removed, the remaining kidney generally is able to perform the work of both kidneys. However, if the remaining kidney is not working well or if both kidneys are removed, dialysis is needed to clean the blood. For a few patients, kidney transplantation may be an option. For this procedure, the transplant surgeon replaces the patient’s kidney with a healthy kidney from a donor.

Arterial Embolization

After arterial embolization, some patients have back pain or develop a fever. Other side effects are nausea and vomiting. These problems soon go away.

Radiation Therapy

The side effects of radiation therapy depend mainly on the amount of radiation given and the part of the body that is treated. Patients are likely to become very tired during radiation therapy, especially in the later weeks of treatment. Resting is important, but doctors usually advise patients to try to stay as active as they can.

Radiation therapy to the kidney and nearby areas may cause nausea, vomiting, diarrhea, or urinary discomfort. Radiation therapy also may cause a decrease in the number of healthy white blood cells, which help protect the body against infection. In addition, the skin in the treated area may sometimes become red, dry, and tender. Although the side effects of radiation therapy can be distressing, the doctor can usually treat or control them.

Biological Therapy

Biological therapy may cause flu-like symptoms, such as chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhea. Patients also may get a skin rash. These problems can be severe, but they go away after treatment stops.

Chemotherapy

The side effects of chemotherapy depend mainly on the specific drugs and the amount received at one time. In general, anticancer drugs affect cells that divide rapidly, especially:

Blood cells: These cells fight infection, help the blood to clot, and carry oxygen to all parts of the body. When drugs affect blood cells, patients are more likely to get infections, may bruise or bleed easily, and may feel very weak and tired.

Cells in hair roots: Chemotherapy can cause hair loss. The hair grows back, but sometimes the new hair is somewhat different in color and texture.

Cells that line the digestive tract: Chemotherapy can cause poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores. Many of these side effects can be controlled with drugs.

Nutrition

Patients need to eat well during cancer therapy. They need enough calories to maintain a good weight and protein to keep up strength. Good nutrition often helps people with cancer feel better and have more energy.

But eating well can be difficult. Patients may not feel like eating if they are uncomfortable or tired. Also, the side effects of treatment, such as poor appetite, nausea, or vomiting, can be a problem. Some patients find that foods do not taste as good during cancer therapy. The doctor, dietitian, or other health care provider can suggest ways to maintain a healthy diet.

Follow-up Care

Follow-up care after treatment for kidney cancer is important. Even when the cancer seems to have been completely removed or destroyed, the disease sometimes returns because cancer cells can remain in the body after treatment. The doctor monitors the recovery of the person treated for kidney cancer and checks for recurrence of cancer. Checkups help ensure that any changes in health are noted. The patient may have lab tests, chest x-rays, CT scans, or other tests.

Support for People with Kidney Cancer

Living with a serious disease such as kidney cancer is not easy. People with kidney cancer may worry about caring for their families, keeping their jobs, or continuing daily activities. Concerns about treatments and managing side effects, hospital stays, and medical bills are also common. Doctors, nurses, and other members of the health care team can answer questions about treatment, working, or other activities. Meeting with a social worker, counselor, or member of the clergy can be helpful to those who want to talk about their feelings or discuss their concerns. Often, a social worker can suggest resources for financial aid, transportation, home care, or emotional support.

Support groups also can help. In these groups, patients or their family members meet with other patients or their families to share what they have learned about coping with the disease and the effects of treatment. Groups may offer support in person, over the telephone, or on the Internet. Patients may want to talk with a member of their health care team about finding a support group

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Results from a small pilot study were presented at the recent American Urological Association’s annual meeting, giving surgeons a sneak peek at a new imaging process that gives healthy kidney tissue a fluorescent glow, clearly differentiating it from cancerous tissue. This glow assists surgeons in the accurate removal of cancerous tissue during a partial nephrectomy, or the removal of a portion of the kidney.

According to the National Cancer Institute, in 2007, it’s estimated that there will be 51,190 new cases of kidney cancer, and almost 13,000 deaths from the disease.

“In general, surgery is the most effective treatment for kidney cancer. Improving surgeons’ ability to see all of the malignant tumor is a significant step forward,” said Edward Messing, M.D., chair of the Department of Urology at the University of Rochester Medical Center.

Indocyanine Green or ICG, a dye that has been widely used for more than 50 years to help diagnose and treat various diseases of the eye, liver and heart, is the source of the guiding fluorescence. The compound, which binds to proteins in the blood, fluoresces and becomes visible once exposed to a laser beam, demonstrating patterns of blood and lymphatic circulation. It’s also very safe when injected into patients, and in fact is approved for use in pregnant women.

Doctors at the University of Rochester Medical Center’s James P. Wilmot Cancer Center recently discovered that when ICG is injected into the kidney during surgery, it clearly shows the boundaries of the cancerous tumor in just seconds, giving surgeons a quick and safe way to definitively mark the margins of cancerous tissue. This allows them to spare as much healthy kidney tissue – and kidney function – as possible.

The study, presented by urologist Dragan Golijanin, M.D., included an analysis of images from ten surgeries on people with cancer of the kidney. The technique outlined each of the tumors with a clarity not often seen in the operating room.

The discovery comes at a time when the number of partial nephrectomies is on the rise. In 2002, 12.3 per cent of all kidney cancer operations were partial nephrectomies, compared with almost 20 per cent today. Physicians are discovering that maintaining maximum kidney function is crucial, especially for older people on medications, who make up most kidney cancer patients. This is a sharp contrast with the traditional approach, which has been to remove the entire kidney – even if it contains only a small, localized tumor – so long as the patient has a second, functioning kidney.

“Sparing even a little bit of kidney tissue, that I might have otherwise taken out, is a very good thing,” said Messing, who performs over 50 full and partial nephrectomies each year and helped author the study. “Now, with the ICG dye process, I clearly see the tumor’s outline and know that I am eliminating as much cancer as possible. I also can see tiny satellite tumors that we never were able to see before. This technique couldn’t come at a better time, as more and more surgeons are opting for partial nephrectomies whenever possible.”

The extensions of many kidney tumors are extremely difficult to spot with the naked eye, so surgeons currently rely on pre-operative imaging, ultrasound and pathology to guide their excisions. Each approach has limitations. Ultrasound images greatly depend on the expertise of the technician, and it adds a step that can be cumbersome during delicate surgery. Preoperative imaging often misses small lesions, can be imprecise with complex tumors, and ineffective in guiding cancer removal when tumors are embedded deep within the kidney. Pathology tests, while very accurate, take time, and cannot point to all cancerous areas, because it’s practical to only test a few samples from excised tissues during the operation (when the surgeon could still remove more kidney needed to get out the entire cancer). So in the end, most surgeons err on the side of caution, removing large chunks of healthy tissue surrounding the tumor to ensure maximum cancer control.

The idea of using a dye that had been floating around in the medical landscape since the 1950s was the brainchild of Golijanin, a resident training under Messing who was searching for a way to illuminate nerves that surround the prostate during prostatectomy surgery. His research led him to articles written by Robert W. Flower, M.D., the physician who first introduced ICG to the medical world some 40 years ago to help diagnose and treat blood circulation problems in the eye. Golijanin noticed a consistent theme in Flower’s writings: Not only did ICG seem to have amazing ‘glowing’ properties inside the blood vessels, but it appeared to attach to other types of tissue as well.

“And so we began to look at ways we could use ICG in prostate surgery, and that has in turn led to a lot of additional discoveries, such as how well it illuminates normal kidney tissue, but not tumors,” Golijanin said. For his development of ICG as an imaging tool, Golijanin and colleagues received the top prize for best scientific manuscript at the World Congress of Endourology in 2006.

“The basic technology has been around for decades, but it’s only recently that we are discovering its potential to differentiate tumors from healthy tissue in a variety of cancers where imaging is not as precise as we’d like it to be,” Golijanin added.

Next on the horizon in the kidney research is to develop a way to illuminate ICG laparoscopically, which will open the door for future use of this technique in other kidney procedures.

In addition, the research team will continue to work with Novadaq Technologies Inc., a Canadian medical devices company, to further explore ways to use ICG to accurately excise a tumor with minimal removal of healthy tissues in prostate, bladder and penile cancers, and in the treatment for a condition known as testicular torsion.

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This reduced risk was seen in people who drank beer, wine or liquor. The findings are in the May 16 issue of the Journal of the National Cancer Institute.

Despite their review, the researchers stressed that not smoking and maintaining a healthy weight are the best ways to reduce the risk of renal cell cancer. They noted that alcohol raises the risk of cancers of the oral cavity, larynx, throat, esophagus, liver and breast, and possibly the colon and rectum.

“These healthy lifestyle choices (not smoking, weight control) should be encouraged, and doing so may also reduce the risk of many other cancers as well as cardiovascular disease,” study author Jung Eun Lee said in a prepared statement.

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Radiofrequency ablation has been used successful in liver tumors since the early 1990s. A needle-like treatment probe, guided by computer tomography (CT), is inserted into the tumor where it emits a high-frequency alternating current. The current heats the tumor tissue and destroys it. Radiofrequency ablation is an outpatient procedure in which the patient is sedated but conscious, and a local anesthetic is used at the puncture site.

The technique targeted tumors ranging in size from 0.6 centimeters to 8.8 centimeters in size. A total of 125 tumors in 104 patients were treated between 2000 and 2006. Of the 95 tumors that were smaller than 3.7 cm, all were completely eradicated by a single treatment, the researchers reported .

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Kidney cancer is a condition in which one or more types of cells in the kidney become cancerous or “malignant”. These cells begin to grow uncontrollably and invade the surrounding tissues. Eventually they spread throughout the body or “metastasize”.

Distinguishing the Types

There are well over a dozen different types of kidney cancers but the most common are Renal Cell Carcinoma (RCC), Transitional Cell Carcinoma (TCC), and Wilm’s Tumor.

Knowing the Causes

It isn’t exactly clear why certain kidney cells become cancerous. At the present time, the best we can do is to identify risk factors associated with kidney cancer.

Learning the Risk Factors

Renal cell carcinoma (RCC) tends to occur when you are older (> 60 years old) and it is more common in men, smokers and the obese. Exposure to dialysis and certain toxins can increase your risk for RCC. The risk factors for transitional cell carcinoma (TCC) are similar to that of bladder cancer. In fact, having one increases your risk chance of having the other. Tobacco and certain chemicals and medications can be particularly important for TCC.

Recognizing the Symptoms

Most kidney cancers do not produce pain and may remain silent until late in the disease. It is estimated that as many as 40% of patients are found to have kidney cancer incidentally found during a radiological procedure done for another reason. The “classic” symptoms talked about in textbooks are blood in the urine, pain in the flank or lower ribcage, and a mass in the abdomen.

Making the Diagnosis

Kidney cancer is usually suspected after a kidney mass is found with an IVP, ultrasound, CT, or MRI. Although these tests can strongly suggest cancer, it is usually necessary to get a biopsy to prove it and determine what type of cancer it is.

Staging of Kidney Cancer

After the diagnosis is made, the cancer is “staged” based on a specific classification system. The staging helps determine both treatment and prognosis.

Treating Kidney Cancer

The treatment options for kidney cancer are pretty limited compared to other cancers. The best treatment is to surgically remove all of it before it spreads. With more advanced treatment, Interleukin-2 is the main chemotherapy agent used.

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RISK FACTORS FOR KIDNEY CANCER

a)      Kidney cancers most commonly occur in adults older than 50 years.

b)      Men are twice as likely to have renal cancers as women are.

c)      Cigarette smoking increases the risk of developing renal cell cancer.

d)      Environmental and occupational exposures to asbestos, cadmium, and organic solvents increase the risk of developing kidney cancer.

e)      Obesity and eating a high-fat diet have been linked with as many as 20% of kidney cancers.

f)        von Hippel-Lindau disease is a genetic condition that has a high incidence of kidney cancer.

SIGNS AND SYMPTOMS

a)      Hematuria (blood in the urine)

b)      Abdominal or low back pain unrelated to injury

c)      Unintentional weight loss

d)      Fatigue

e)      Anemia (low red blood cell count)

f)        Fever

g)      High blood pressure

h)      Leg or ankle swelling

TESTING FOR KIDNEY CANCER

Diagnosis of renal cancer may involve several kinds of tests. In addition to a detailed medical history, physical examination, and laboratory blood testing, tests may include a computed tomography (CT) scan, ultrasound, magnetic resonance imaging (MRI), or intravenous pyelography (a dye and x-ray test of the kidneys). Chest x-ray and bone scan may be used to detect metastatic disease. Arteriography, a technique that uses dye in the blood vessels feeding the kidney, may define the extent of the tumor or help plan surgical treatment.

TREATMENT

Surgical removal of the kidney (nephrectomy) and surrounding tissue may cure kidney cancer in persons whose tumor is confined to the kidney. Radiation therapy (high-energy x-ray treatments) may be offered to patients to treat pain and advanced or metastatic kidney cancers or to help shrink a tumor that is causing obstruction. Immunotherapy helps to boost the body’s own immune system to fight the cancer. Interferon and interleukin 2 boost the immune system and may be used to treat patients with advanced kidney cancer. Patients who volunteer for clinical trials (medical research studies) may be offered immunotherapy in combination with experimental treatments.

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Now, a publication issued by the European Association of Urology (EAU) at the association’s annual meeting in March 2007, gives cause for hope (1). Experts in the treatment of mRCC, writing on the latest research findings, say that new, more effective, drugs have the potential to change the outcome of the disease radically. “We are in a position to change the natural history of this disease by transforming mRCC into a chronic disease” say the authors led by Professor Jean-Jacques Patard of Rennes University Hospital, Rennes, France (1).

Their optimism stems from the development of small molecule drugs, swallowed as tablets, that are able to target receptors on and within cancer cells, inhibiting kinases (specialised enzymes) with the effect of arresting growth and depriving tumours of their blood supply. Much more work needs to be done to identify combinations of drugs that will put cancers into complete remission and prevent metastases recurring after surgery, the authors warn, but they say there are already two drugs that can make a major contribution beyond the standard treatments already used.

Sunitinib (Sutent) manufactured by Pfizer was shown in a large phase III clinical trial of 750 mRCC patients with a low or intermediate risk to extend the time period before their disease progressed. Patients received either sunitinib or the standard therapy of interferon (IFN) alpha. Those receiving sunitinib more than doubled the length of their progression-free survival to 11 months compared to 5 months for IFN alpha. Their risk of dying or seeing their disease worsen was more than halved (58%). Tumours were more than five times more likely to shrink when treated with sunitinib than with IFN alpha. Response rates were 31 per cent versus 6 per cent. These results were highly statistically significant. What is more, patients felt their quality of life was improved more by sunitinib than IFN alpha and a smaller number of them experienced side effects causing treatment to be withdrawn. Although the results are not yet available to show how treatment affects length of survival overall, the data are encouraging.

New EAU guidelines recommend first-line use

The results of the sunitinib trial have meant that the drug is now officially approved in Europe and America for first-line use in mRCC. Within two months of Pfizer receiving permission to promote the drug in this indication, the EAU has already advocated its use as first-line therapy in its latest guidelines. Professor Kurt Miller, a member of the German Working Group for Urological Cancer, who is based in Berlin said the EAU’s first-line sunitinib recommendation was an important step in getting the therapy acknowledged as the standard of care for mRCC therapy across Europe. Physicians in some European countries are likely to encounter reluctance in willingness to fund the treatment costing around €3000 per patient per month but Professor Miller said: “There is strong clinical evidence to support its use.”

The second major contribution highlighted, concerned another targeted therapy, temsirolimus, in development by Wyeth as Torisel. The drug is a specific inhibitor of M tor (mammalian target of rapamycin), a kinase that plays a key role in cell cycle regulation. A phase III study of mRCC patients with poor prognosis, comparing first-line temsirolimus with IFN alpha, showed temsirolimus extended median survival by 49 per cent (10.9 vs 7.3 months). The product is not yet licensed but when it receives marketing approval the EAU guidelines recommend that clinicians should consider it for first-line treatment of poor-risk mRCC patients.

Further research is already in progress to explore the optimal combinations of targeted therapies and how they can best be used to help patients keep their cancers suppressed for much longer than has been possible to date. More data is likely to be available later this year.

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Radiation may be used as a palliative treatment, to ease pain and other symptoms of advanced kidney cancer that has spread to bone or other areas of the body.

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Two drugs approved for use in the US since December 2005, however, have demonstrated benefit in shrinking kidney cancer tumors and also in delaying the time it takes for new tumors to develop. The drugs, marketed under the brand names Nexavar and Sutent, are not cures for the disease, but a Medical College of Wisconsin cancer specialist explains that they have already had a significant impact in the field of renal cell carcinoma treatment and may ultimately prove to extend survival time for patients.

“We are on the right track, learning more all the time about the biology of kidney cancer tumors and about how to disrupt that biology,” said Nancy B. Davis, MD, Medical College Assistant Professor of Medicine. “Kidney cancer is pretty rare in the US and in the rest of the world. Although there are a couple different kinds of kidney cancer; the most common kind is sporadic, meaning that it is not genetically transmitted.

“There is a hereditary form of kidney cancer that involves a particular genetic mutation. Those cancers tend to occur early, in people in their 30s or 40s, and tend to be hereditary, meaning that other family members have had that kind of kidney cancer. The vast majority of kidney cancer, however, is not hereditary.”

While kidney cancer may be rare compared to other cancers, the National Cancer Institute (NCI) of the National Institutes of Health estimates that in the US more than 51,000 new cases will be diagnosed and nearly 13,000 people will die from the disease in 2007.

Usually Detected in Advanced Stage

“The risk factors for kidney cancer are not well defined,” said Dr. Davis, “although we do know that smoking is related to kidney cancer and that some toxin and chemical exposures can lead to kidney cancer. But overall it is difficult to determine why a particular person got kidney cancer. Most of the time we can’t make that determination.

“Kidney cancer typically grows slowly. The classic literature will tell you that the tumors present with blood in the urine, back pain, an abdominal mass. But that happens in less than 10% of the people with kidney cancer. A tumor must grow large enough to cause any of those findings, so these findings don’t occur until late, if ever. When we find kidney cancer, it usually has been asymptomatic (presenting no obvious signs of disease), and may be quite large and quite advanced.

“A very early diagnosis is needed in order to cure kidney cancer. It can be cured if detected soon enough, with surgery to completely remove the tumor. But even in patients with early-stage disease, small tumors less than four centimeters that can be taken out completely, about 5% will recur. Once it is metastatic (moves to other areas) it is rarely curable.”

Chemotherapy Agents Have Little Impact

In simple terms, kidney cancer kills by spreading to other parts of the body and causing organ failure. It is most often treated with radical nephrectomy, in which a surgeon removes the entire kidney, possibly the adrenal gland and some tissue around the kidney. In Stage 1 kidney cancer patients, simple nephrectomy may be employed to remove just the kidney. Patients with only one kidney or with cancer in both kidneys, or with small tumors of less than 4 centimeters (about three-quarters of an inch) may have a partial nephrectomy, with only a part of the kidney removed.

Other kidney cancer treatments include arterial embolization (a substance is injected into the renal artery that inhibits blood flow and thereby starves the tumor of oxygen and other things it needs to grow), radiation therapy (high-energy rays used multiple times over several weeks to kill cancer cells), and immune therapy (using the immune system’s natural ability to fight cancer by introducing large quantities of interleuken-2, which is normally produced in the body in small amounts to fight infection and disease). The use of immune therapy is decreasing since the approval of newer, more targeted, drugs.

Kidney cancer is essentially non-responsive to chemotherapy, a mainstay of treatment for many other cancers. “Kidney cancer does not respond to typical chemotherapy agents that we consider for disease like breast cancer or lung cancer,” said Dr. Davis. “Those agents get into the cell and stop cells from growing and dividing by intercalating into their genetic code.

“When a cancer cell is growing very slowly, cell division is not taking place and the cells are not susceptible to intercalating agents. Chemotherapy agents don’t work well in slow-growing tumors, including kidney cancer and myeloma (a primary tumor of the bone marrow). If the drugs can’t get in, it’s hard to kill it.”

Nexavar and Sutent Block Cell Growth

The immune-modulating medication interleuken-2 has low response rates, said Dr. Davis. Statistically, she said, only about 15 out of every 100 kidney cancer patients will have shrinkage in their tumor using high-dose interleuken-2 and, out of those 15 patients; fewer than one may have a prolonged remission or potential cure. For a variety of reasons, including significant side effects, only a very select group of young, otherwise healthy patients are candidates for interleuken-2 treatment.

Survival rates among kidney cancer patients are similarly grim. While by no means certain in terms of accuracy for any individual patient, said Dr. Davis, patients with metastatic kidney cancer but with none of the characteristics in a validated five-factor predictive model have a median survival of 20 months, patients with one or two of the five factors fall into a survival range of about 11 months, and patients with three or more of the factors have a median survival of 4 months.

Having new drugs that show promise for providing benefit to a higher percentage of kidney cancer patients is a big step forward, said Dr. Davis. She noted that the Medical College was involved in the global study just prior to Nexavar’s approval and is currently engaged in other major kidney cancer studies. One is a trial of the two new drugs in the post-operative setting “to see if we can decrease the recurrence rate in patients who are at higher risk,” and the others involve earlier phases of research into two other new agents.

“Nexavar and Sutent are both orally available medications that block cell growth and proliferation at a molecular level,” said Dr. Davis. “They target receptors called tyrosine kinases on the cancer cells. Blocking these targets prevents new blood vessel formation and tumor proliferation/growth. These medications really have radically changed the treatment of renal cell carcinoma. We have two more therapies, in addition to immune therapy, that, while they do not cure kidney cancer, are fairly well tolerated and can provide tumor response (meaning shrinkage of tumor) and also delay time-to-tumor progression. While neither drug has statistically met a survival endpoint, with further follow up they may prolong life in an advanced kidney cancer population.

“It’s a very exciting time in kidney cancer treatment development and research. Just in the past 18 months we’ve gone from having pretty ineffective yet highly toxic therapies to offer, to having two oral drugs which are fairly well tolerated and do show benefit. Currently there are ongoing clinical trials investigating newer agents and new combinations of agents. We don’t have a cure, so we’re not anywhere near the end of research and development for this disease. But the new agents that are available now and those coming along provide us further options for these patients.”

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