Patient information: Renal (kidney) cell cancer

RENAL CELL CANCER OVERVIEW

Renal (kidney) cell cancer is a condition in which one or more cancerous tumors develop in one or both kidneys (figure 1). Over time, the tumors grow in size and can invade surrounding tissues. In its more advanced stages, renal cancer can metastasize (spread throughout the body), causing tumors to develop in other organs.

TYPES OF RENAL CELL CANCER

Renal cancer can be primary, meaning that the tumor first developed in the kidney. The kidneys can also develop metastatic or secondary tumors as a result of cancer that spreads from some other part of the body.

There are several types of primary renal cancer:

• Renal cell carcinomas (RCCs) comprise 80 to 85 percent of all renal cancers; they typically arise in the renal cortex (the outer layer of the kidney, (figure 2).
• Transitional cell carcinomas arise within a portion of the kidney called the renal pelvis (figure 2), where the urine collects before being transported to the bladder for storage. These types of tumors are more closely related to bladder cancer than to renal cancers, and they are treated similarly. (See "Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer".)

• Wilms tumor, also called nephroblastoma, is another type of kidney tumor that is found most commonly in children. (See "Presentation, diagnosis, and staging of Wilms tumor" and "Treatment and prognosis of Wilms tumor".)

Here we will focus on the symptoms, diagnosis, and treatment of primary renal cell carcinoma.

RENAL CELL CANCER RISK FACTORS

Primary RCC is most common in people over age 50. It is more common in men than in women, and in blacks as compared to white (non-Hispanic) people. Although the cause of kidney cancer is usually not known, certain factors can increase your risk.

• Cigarette smoking — Cigarette smoking doubles the risk of developing RCC.
• Chemical exposure — Exposure to substances in the workplace, such as cadmium, asbestos, and petroleum by-products increases the risk for RCC.
• Obesity — Increased body weight appears to be associated with an increased risk for RCC in both men and women.
• Acquired cystic disease of the kidney — Acquired cystic disease of the kidney develops in a large percentage of patients who are on chronic dialysis because of kidney failure. Approximately 30 percent of patients with acquired cystic disease will develop RCC.
• Medication overuse — Prolonged use of medicines containing aspirin and a compound called phenacetin (banned in the United States since 1987) can lead to kidney failure, and also increases the risk of renal cancers.
• Genetic factors — Certain inherited disorders such as von Hippel-Lindau syndrome, Birt Hogg Dube syndrome, and tuberous sclerosis are associated with an increased risk for RCC.

Periodic screening of the urine or abdominal ultrasound may be recommended for people with an inherited risk of RCC. This includes patients with von Hippel-Lindau syndrome, Birt Hogg Dube syndrome, tuberous sclerosis, those who have been on dialysis for several years, and those with a strong family history of RCC.

RENAL CELL CANCER SYMPTOMS

The most common early symptoms of RCC are:

• Hematuria (blood in the urine)
• Flank pain (pain in the side at the lower ribcage)
• A new growth in the abdomen

However, most renal cell cancers do not cause pain, and many patients with RCC have no symptoms until the disease is advanced.

RENAL CELL CANCER DIAGNOSIS

If a kidney cancer is suspected, an abdominal CT scan is usually performed to see the size and location of the tumor and determine whether the tumor has invaded surrounding tissues and organs.

Other studies, including a CT scan of the chest, a bone scan, and an abdominal MRI may also be performed to determine if the cancer has grown beyond the kidney.

RENAL CELL CANCER STAGING

After the diagnosis of RCC is confirmed, the cancer is staged. Staging is a system used to describe the aggressiveness and spread of a cancer. Staging information is useful in determining treatment and prognosis. In general, patients with earlier stage disease have the most favorable prognosis or outcome.

In broad terms, the stages of RCC are as follows:

• Stage I — Patients with stage I RCC have a small (less than 7 cm) tumor that is limited to the kidney. The lymph nodes are not involved.
• Stage II — Patients with stage II RCC have a larger (greater than 7 cm) tumor that is limited to the kidney.
• Stage III — In patients with stage III disease, the tumor has invaded the adrenal gland (which sits atop each kidney), tissues surrounding the kidney, or major nearby veins, such as the vena cava. Stage III disease also includes patients with enlarged abdominal lymph nodes.
• Stage IV — Patients with stage IV disease are those who have large tumors that extend into surrounding tissues, and/or metastases to other distant locations.

RENAL CELL CANCER SURGICAL TREATMENT

Treatment for renal cell cancer may include surgery, radiation therapy, or medications such as immunotherapy or targeted therapy.

Surgery — Surgery is an option for people with early RCC (stage I, II or III disease). When the cancer has not spread beyond the kidney, surgery offers a reasonable chance for a cure. Several types of surgery may be considered, including radical or partial (nephron-sparing) nephrectomy.

Radical nephrectomy — Radical nephrectomy is generally recommended for tumors larger than 4 cm. The procedure requires removal of the entire kidney. The remaining, normal kidney takes over the function of filtering the blood to remove toxins and excess water. The nearby adrenal gland and regional lymph nodes may also be removed in this procedure, and parts of adjacent organs that are involved with the cancer may also be removed.

Partial nephrectomy — In a partial nephrectomy, the tumor and some of the surrounding kidney tissue are removed. Partial nephrectomy is generally preferred for smaller kidney tumors.

Cryoablation and radiofrequency ablation — Other procedures may be recommended if partial and radical nephrectomy are not an option. These include:

• Cryoablation (destroying the tumor by a freezing technique)
• Radiofrequency ablation (RFA, destroying the tumor by using radiofrequency heat energy).

Surgery in patients with advanced RCC — For patients who have more advanced disease, surgery is sometimes performed in conjunction with medical therapy (see 'Renal cell cancer medical therapy' below. For example, in some patients with advanced disease, the response to immunotherapy may be enhanced by removing the kidney tumor. This is referred to as debulking or cytoreductive surgery; the goal is to remove as much of the tumor as possible so that immunotherapy is more likely to slow or stop growth of the cancer.

Similarly, surgical removal of metastatic tumors (outside the kidney, particularly those involving the lungs) may be helpful.

RENAL CELL CANCER MEDICAL THERAPY

RCC is often silent until it has reached an advanced stage, meaning that surgery is not an option. Medical (ie, non-surgical) treatment may be recommended for people who are diagnosed with advanced RCC and those whose cancer has recurred (grown or spread) after surgery.

Interleukin-2 immunotherapy — Immunotherapy is the standard medical treatment of advanced renal cancer. The immune system helps to fight and protect the body from harmful substances. The immune system is triggered when it detects a "foreign" substance. Renal tumors may be recognized as foreign substances, which increases their sensitivity to therapies that activate the immune system.

Removal of the kidney (debulking) — Surgical debulking procedure is recommended for some people before immunotherapy since this improves the chances of responding to immunotherapy.

Interleukin-2 — The most active immunotherapy drug used to treat RCC is interleukin-2 (IL-2). High dose IL-2 was previously the standard treatment for advanced RCC. However, it can cause serious, even toxic side effects, and some patients are not able to tolerate it. When completed, IL-2 produces tumor shrinkage in 15 to 20 percent of patients, with nearly half of the tumor responses being complete and many being long-lasting [1].

High-dose IL-2 is considered by many to be the preferred treatment for people with advanced RCC who are able to tolerate it. Experts are working to identify the group of people who will benefit from high dose IL-2, with the hope that the treatment would only be give to those who are most likely to benefit.

Side effects of IL-2 — High dose IL-2 can cause serious side effects, and patients must be treated in the hospital and closely monitored (often in the intensive care unit) during therapy. Common side effects include flu-like symptoms (muscle and joint aches, low grade fever, chills), nausea, vomiting, diarrhea, low blood pressure, shortness of breath, confusion, skin rash, and a temporary drop in the platelet count.

Targeted therapy — Several medicines have been developed that target the differences between tumors and normal tissue. These are called targeted drugs, and include sorafenib, sunitinib, temsirolimus, everolimus, and bevacizumab. These targeted drugs do not produce long-term remission or cure, but they can slow the growth of the cancer.

Chemotherapy — Renal cell cancer is generally resistant to chemotherapy, although it may be used in people with certain types of RCC.

RENAL CELL CANCER SYMPTOM MANAGEMENT

People with advanced RCC often need treatment for pain and other symptoms. Pain is often treated with pain medications. Blood clots can sometimes develop in the urinary tract and cause spasms. Spasms may be treated with IV fluids or by having a stent (a thin tube) inserted into the urinary tract to keep it open and allow clots to pass through.

Therapeutic embolization — Kidney cancers often cause bleeding since they contain a large blood supply. Embolization is a procedure in which a gelatin-like substance is injected into selected blood vessels near the kidney cancer. The gelatin forms a barrier that blocks blood flow to the area fed by the blood vessels.

Embolization may be done to lower the risk of hemorrhage (heavy bleeding) during nephrectomy in people with large tumors. It is also used to control symptoms, such as bleeding and pain, in people who are not candidates for surgery or who have metastases.

Radiation therapy — Tumors that metastasize to areas outside the kidney can cause pain. Radiation treatment can be used to relieve pain from metastatic tumors. At sites such as the brain and lungs, radiation therapy is used to reduce the size of the tumor.

CLINICAL TRIALS

Progress in treating renal cell cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

       www.cancer.gov/clinical_trials/learning/

       http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Bladder cancer treatment; non-muscle invasive (superficial) cancer

Professional Level Information:
Acquired cystic disease of the kidney in adults
Clinical features, diagnosis, and management of von Hippel-Lindau disease
Clinical manifestations, evaluation, and staging of renal cell carcinoma
Epidemiology, pathology, and pathogenesis of renal cell carcinoma
Evaluation of a solid renal mass
Immunotherapy of renal cell carcinoma
Molecularly targeted therapy for advanced renal cell carcinoma
Overview of the prognosis and treatment of renal cell carcinoma
Surgical management of localized renal cell carcinoma
Surveillance for metastatic disease after nephrectomy for renal cell carcinoma
Presentation, diagnosis, and staging of Wilms tumor
Treatment and prognosis of Wilms tumor

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (www.niddk.nih.gov)

• National Cancer Institute

      (www.nci.nih.gov/)

• American Cancer Society

      (www.cancer.org)

• National Kidney Foundation

      (www.kidney.org)

• Kidney Cancer Association

      (www.kidneycancerassociation.org)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)

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