Renal Cell Carcinoma

Treatment Options

Your doctor and other members of your health care team will help you learn more about the many treatment options available for renal cell carcinoma (RCC). Surgery and radiation therapy are considered local therapies, and chemotherapy, immunotherapy and targeted therapy are considered systemic therapies because the drugs travel throughout the body via the bloodstream. These types of treatment can be used alone or in combination with each other. Your specific treatment plan will be selected according to several factors, including the type of RCC, the stage of disease, the location of the tumor(s), your overall kidney function and your general health.

Surgery

RCC is typically treated with surgery to remove either part of the kidney (partial nephrectomy) or the entire kidney (radical nephrectomy). The type of surgery that’s best for you depends on the size and stage of the cancer, whether you have one or two kidneys and whether tumors are present in one or both kidneys.

For a partial nephrectomy, the surgeon removes only the cancerous tumor, as well as some of the kidney tissue around the tumor. The goal of a partial nephrectomy is to preserve kidney function and decrease the risk of complications compared with a radical nephrectomy. In addition, research has shown that a partial nephrectomy provides outcomes similar to those after a radical nephrectomy. Because of this, more people with RCC are now being treated with a partial nephrectomy.

However, a radical nephrectomy is still needed in some cases, especially for large tumors or when the tumor has spread beyond the kidney. With this procedure, the surgeon removes the entire kidney, some nearby fatty tissue and, in some cases, the attached adrenal gland as well. Many people will still have normal kidney function with only one kidney. During the procedure, the surgeon will often remove some of the surrounding lymph nodes to more accurately stage the cancer and predict prognosis.

A partial or radical nephrectomy can be done with one of three techniques.

  • Open surgery. Using this approach, the surgeon removes the tumor or kidney through a large incision in the abdomen or the flank (side). After the procedure, the incision is closed with stitches.
  • Laparoscopic surgery. This less-invasive technique involves passing a laparoscope (a wand-like camera) and small instruments through a series of small incisions in the wall of the abdomen to remove the tumor or kidney. Laparoscopic surgery can preserve the muscles and/or nerves in the area and generally offers a shorter recovery time and fewer postoperative complications than open surgery.
  • Robotic-assisted surgery. With this approach, the surgeon controls a robotic system that includes a camera and small instruments that are inserted into the body through several small incisions. Like laparoscopic surgery, robotic-assisted surgery is less invasive than open surgery. This type of operation provides a wider view of the kidney and nearby area than laparoscopic surgery.

Studies have shown that the outcomes are similar for all three surgical approaches when done by surgeons who have expertise in the specific techniques, so talk to your doctor about which choice is best for you. With any of these operations, you will receive a general anesthetic to keep you asleep and pain-free during the surgery. In general, people who have surgery stay in the hospital approximately four to seven days.

A cytoreductive nephrectomy is surgery to remove the entire kidney with the primary tumor when metastatic disease is present (disease that has spread to distant parts of the body). It is not always possible to remove all of the cancer if there are many metastases, but removing some of the cancer can still be helpful for some people. A metastasectomy is surgery that may be used when the primary tumor can be completely removed and there are only a limited number of metastases. This approach works best for metastases in the brain, bone or lung.

Active Surveillance

Instead of doing surgery, doctors may choose to perform a biopsy on a small kidney tumor, then watch it closely to see if it grows. This option may be used for people with kidney tumors that are less than 4 centimeters, which is about 1.5 inches. This approach is often used for older people or those who are not healthy enough for surgery. If the tumor grows quickly or becomes larger than 4 centimeters, the tumor will be removed or treated in another way.

Arterial Embolization

Arterial embolization is not done often, but it’s an option when surgery to remove the cancer is not possible. This procedure blocks the main blood vessel that feeds the kidney so that the tumor will starve and eventually shrink.

Ablative Techniques

Ablative techniques are alternatives to surgery. One ablative technique is cryoablation. With this procedure, the surgeon inserts a hollow needle into the tumor through the skin or during laparoscopic surgery, and then passes cold gas through it. The extreme cold produces an ice ball that kills the tumor. Another ablative technique is known as radiofrequency ablation. Instead of cold gas, the surgeon passes high-energy radio waves through the needle to heat the tumor and kill the cancer cells. Ablative techniques are not standard treatment for RCC, but they may be used for older individuals or for people with other health risks.

Radiation Therapy

Radiation therapy is the use of high-energy X-rays to kill cancer cells. RCC typically doesn't respond well to radiation therapy, but it’s sometimes used for people who cannot have surgery because of health problems. More often, radiation therapy is used to relieve the symptoms of RCC, including bleeding, pain and problems related to metastasis to the bones or brain. If your doctor includes radiation therapy in your treatment plan, a radiation oncologist will oversee it. He or she will carefully plan your radiation therapy to calculate the appropriate dose and determine the optimum treatment schedule before treatment begins.

Chemotherapy

Chemotherapy drugs, also called cytotoxic drugs, are used to stop the growth of cancer cells. Chemotherapy is sometimes referred to as conventional chemotherapy to distinguish it from targeted therapy, which relies on more recently developed drugs that target specific molecules in RCC. RCC is generally resistant to standard chemotherapy; however, these drugs can be more effective for certain RCC subtypes, especially when used in combination with other chemotherapy drugs (see Commonly Prescribed Medications for RCC below).

Targeted Therapy

Researchers have learned about the cell pathways that can lead to many types of cancers and also have learned how to develop drugs that block those pathways. These drugs are known as targeted drugs (or agents), and treatment is known as targeted therapy. Although all cancer treatments target specific pathways, these targeted therapies are directed at more recently recognized targets, which are often more specific to the cancer cells or the mechanisms encouraging their growth. Targeted therapy drugs block the signals that proteins and other molecules send, which direct basic cancer cell functions, such as cell growth, division and death.

Effective targeted therapy (and, in fact, any therapy) depends on two factors: identifying targets that play an important role in the growth and survival of cancer cells, and developing agents that can attack those targets. Two important targets for RCC that researchers have identified are vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). These growth factors activate proteins in and around the cancer cells that stimulate new blood vessel growth; these blood vessels then help tumors grow and spread. Targeted therapy drugs have been developed to inhibit these proteins in order to delay cell growth and possibly shrink tumors.

Targeted therapy drugs are widely used as first-line and second-line therapies for advanced RCC (see Commonly Prescribed Medications for RCC below). First-line therapy is any treatment that is given first; second-line therapy is given if the first-line therapy fails.

Cancer cells often become resistant to targeted therapy drugs, making the drugs less effective over time. Researchers continue to explore ways to overcome resistance, identify new pathways to target and develop new agents to interrupt the growth of RCC cells (see Clinical Trials).

Immunotherapy

Immunotherapy uses the body’s immune system to help fight RCC cells. Different types of immunotherapy, including checkpoint inhibitors and cytokine therapy, involve promoting, strengthening or re-engaging an immune response against RCC. The checkpoint inhibitor used to treat RCC targets PD-1, a protein on immune system cells called T-cells that normally helps keep these cells from attacking other cells in the body. By blocking PD-1, the checkpoint inhibitor boosts the immune response against cancer cells. This can shrink some tumors or slow their growth. Used as second-line therapy to treat RCC, this checkpoint inhibitor is given intravenously (through a vein in the arm or hand).

Cytokines are proteins in the body that activate the immune system. The biologic drugs used in cytokine therapy are versions of those proteins that have been made in a laboratory. The goal of cytokine therapy is to shrink the RCC tumor or slow its growth. These biologic drugs are used only in a small percentage of people with RCC because the drugs can have serious side effects and are often not effective in getting a response from the tumor. However, when a response does occur, it may be long-lasting. Cytokine therapy is given either intravenously (through a vein in the arm) or subcutaneously (by injection under the skin) and may be used in combination with or following targeted therapy.

Commonly Used Medications

Chemotherapy
floxuridine
fluorouracil – also known as 5-FU
Immunotherapy
interferon alfa
interleukin-2 (Aldesleukin, Proleukin)
ipilimumab (Yervoy)
nivolumab (Opdivo)
pembrolizumab (Keytruda)
Targeted Therapy
axitinib (Inlyta)
bevacizumab (Avastin)
bevacizumab-awwb (Mvasi)
cabozantinib (Cabometyx)
everolimus (Afinitor, Afinitor Disperz)
lenvatinib (Lenvima)
pazopanib (Votrient)
sorafenib (Nexavar)
sunitinib (Sutent)
temsirolimus (Torisel)
tivozanib (Fotivda)
Some Possible Combinations
avelumab (Bavencio) with axitinib (Inlyta)
axitinib (Inlyta) with pembrolizumab (Keytruda)
nivolumab (Opdivo) and cabozantinib (Cabometyx, Exelixis)

As of 3/11/21

Oral and Intravenous Treatment Medications

Some drugs to treat RCC are taken orally (by mouth), and others are given intravenously (through a vein in the arm or hand). These treatments are considered “systemic” because the drugs travel through your entire body to kill cancer cells; because of this, some of the side effects can be similar (see Side Effects).

Oral Medications

Oral medications can be in many forms, including liquid, tablet or capsule. Your treatment team will provide you with clear instructions on how to take your oral drugs, but it's up to you to follow those instructions at home. You will see your treatment team at regular intervals to track how the RCC is responding to the medications, but the success of the treatment depends in part on medication adherence.

Medication Adherence

Medication adherence refers to the extent to which a person follows instructions and guidelines for medications, as prescribed by the health care provider.

There are four key factors to proper medication adherence:

  1. Taking the right drug
  2. At the right dose
  3. At the right time
  4. On the right schedule

When people don’t follow their scheduled regimen exactly as prescribed, it’s called nonadherence. Most often, nonadherence is unintentional. If you miss one or more doses of your medication because you forgot to take it, let your health care provider know. If you are frightened about side effects, be sure to discuss your concerns with your medical team so they can assist you with your adherence.

Intentional nonadherence includes deliberately not refilling your prescriptions or taking less than recommended. Nonadherence can have a serious impact on your cancer care and can lead to increased side effects, unnecessary changes to the treatment plan, hospitalization and poor outcomes.

The most serious consequence of medical nonadherence is running the risk that your treatment will be ineffective. Studies show that not taking cancer medication as prescribed by a doctor can lead to cancer progression or recurrence. Because of how the drugs work, even small alterations to a treatment regimen can lead to failure.

It’s important to stick to your treatment plan exactly as your doctor prescribed. The only people who should alter it are members of your health care team. Treatment regimens are the most beneficial if decisions are shared by you and members of your health care team, so communicate often with them about any questions or concerns you have to be sure you’re taking your medication as prescribed.

Intravenous Medications

Intravenous (IV) treatments can be given as either a short infusion (an “IV push”), in which the drugs are pushed from a syringe through a catheter (slender tube) for just a few minutes, or by an IV infusion, in which a drug solution steadily flows into your body for anywhere from a half hour to several hours.

On the day of your IV treatment, you may want to bring a friend or family member with you for support, and/or something to keep you busy, such as a book or knitting materials.

When you arrive at the medical facility, you will meet the health care professional who will give you your treatment. He or she will check your vital signs (temperature, blood pressure, pulse and respirations), measure your height and weight, and insert the IV catheter into a vein in your arm. You may have a blood sample drawn and tested to make sure your body is strong enough to receive treatment that day. (A sample of blood may be drawn instead before your vital signs are checked.) After the initial discomfort of the needle stick, you usually don’t feel any pain, burning, coolness or anything unusual as the drug infuses.

When your treatment session ends, the health care professional will remove the IV catheter and needle and discuss the potential side effects again. It can be helpful to drink plenty of fluids for several hours after your treatment to flush the drugs through your body. Talk to your doctor about what to expect from your specific treatment plan.

Questions to Ask Your Doctor When Discussing Treatment Options

  • Who will be coordinating my RCC treatment?
  • What is the goal of each of my treatment options?
  • How do the benefits of the recommended cancer treatment compare with the risks?
  • Are there any clinical trials open to me?
  • Will I need to be hospitalized for the treatment or is it done in an outpatient clinic?
  • What is the expected timeline of each treatment plan?
  • How will each treatment affect my daily life?
  • Is there a way to decrease the possibility that side effects will occur?
  • Are there medications available to relieve or prevent side effects?
  • How can I keep myself as healthy as possible during treatment?
  • What resources are available to me?

Second-Line Therapy

It’s important to talk to your doctors and nurses about your cancer care throughout the entire treatment process. Asking questions about all of your treatment options allows you to make more informed decisions about your comprehensive care every step of the way.

A cancer treatment plan is selected depending on which options are most likely to have the greatest benefit with the fewest side effects and risks. The plan for this initial treatment, known as first-line therapy, is most often determined based on the results of clinical trials involving patients with a similar cancer diagnosis. Every individual has a different response to treatment, so what may work for others may not always be the best option for you. If your first-line therapy is not successful, stops working at any point, or causes unmanageable or dangerous side effects – or if other health conditions prevent you from continuing – you should talk to your doctor about subsequent treatment options, known as second-line therapy.

Several factors influence the potential success of a second-line therapy, including your cancer type, stage, age, overall health and treatment history, including what treatments you’ve had already and how your disease responded (effectiveness, side effects, etc.). If you and your oncologist need to discuss second-line therapy options, the following questions may be helpful to get the conversation started:

  • Is there a second-line therapy available, and how is it different from the first-line therapy?
  • How does the dosing of the second-line therapy differ from that of previous treatments?
  • What is the goal of this treatment (to eliminate the cancer, alleviate symptoms, or both)?
  • What are the risks, benefits and potential side effects?
  • What is the success rate of this treatment for my cancer type?
  • What is my prognosis if I choose not to have second-line therapy?