Treatment Update: Kidney Cancer

Surgery

Surgery is the primary treatment for kidney cancer that has not spread to other parts of the body.

Depending on the stage and location of the cancer and other factors, surgery may remove the tumor or tumors along with some of the surrounding kidney tissue (known as a partial nephrectomy), or the entire kidney (known as a radical nephrectomy). The adrenal gland (the small gland that sits on top of each kidney) and fatty tissue around the kidney may also be removed.

A laparoscopic approach is often used in surgery. With this approach, the surgeon makes several small incisions in the abdomen. A tiny light, camera and surgical instruments are inserted into the incision to view and remove the tumor. In many cases, laparoscopic surgery has been shown to be as effective as traditional surgery, with an easier recovery. Before deciding on an approach, discuss the risks and benefits of traditional versus laparoscopic surgery with your surgeon.

If the cancer has spread (metastasized) and formed tumors in other parts of the body, the original tumor in the kidney can sometimes still be treated with surgery, followed by other forms of treatment.

Targeted Therapy

Targeted therapies focus on specific molecules and cell mechanisms thought to be important for cancer cell survival and growth, taking advantage of what researchers have learned in recent years about how kidney tumors grow.

• Temsirolimus (Torisel) and everolimus (Afinitor) work by blocking the actions of mTOR, a protein which activates mechanisms in cells that promote cancer growth.
• Tivozanib (Fotivda) treats relapsed (recurred) or refractory (not responding to treatment) advanced kidney cancer following two or more prior therapies. Tivozanib blocks protein kinases, an enzyme that can lead to the growth of cancer cells.

Some targeted therapies are designed to stop angiogenesis (blood vessel growth). Between 2005 and 2012, five anti-angiogenesis drugs were approved by the FDA for the treatment of metastatic kidney cancer:

• Sunitinib (Sutent), pazopanib (Votrient), axitinib (Inlyta) and sorafenib (Nexavar) work by blocking the action of proteins released by tumors which promote the formation of blood vessels, thereby “starving” the tumors. The protein pathways that are blocked include vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).

  • Sunitinib is also approved for the treatment of people who underwent a radical nephrectomy and are at high risk of kidney cancer recurrence.

• Bevacizumab (Avastin) acts by binding directly to and inactivating VEGF.

There are three targeted therapies approved by the FDA to treat people with advanced kidney cancer who previously received anti-angiogenic therapy:

• Cabozantinib (Cabometyx), a drug that targets multiple tyrosine kinases (enzymes that are part of many cell functions, including growth and division). At too-high levels, these enzymes can be involved in the development of renal cell carcinoma, and blocking them may help keep cancer cells from growing.

• Lenvatinib (Lenvima) in combination with everolimus (Afinitor); this is the first regimen that targets both tyrosine kinases and the protein mTOR.

• Belzutifan (Welireg), following treatment with a PD-1 or PD-L1 inhibitor (see Immunotherapy section) and a VEGF inhibitor. Belzutifan works by preventing the accumulation of HIF-2α, a protein associated with tumor growth.

Immunotherapy

Our immune system works constantly to keep us healthy. It recognizes and fights against danger, such as infections, viruses and growing cancer cells. In general terms, immunotherapy uses our own immune system as a treatment against cancer.

• Nivolumab (Opdivo) is for the treatment of people whose metastatic kidney cancer progressed while on an anti-angiogenic therapy (treatments designed to prevent the development of blood vessels). Nivolumab works by interfering with a molecular “brake” known as PD-1 that prevents the body’s immune system from attacking cancer cells. Cancer cells take advantage of PD-1 by expressing another molecule called PD-L1, which directly interacts with PD-1 to protect cancer cells from the body’s immune system.
• Combination of nivolumab and ipilimumab (Yervoy). Ipilimumab is thought to help the immune system destroy cancer cells by blocking the action of CTLA-4, a protein that normally helps keep immune system cells (called T-cells) in check.

Chemotherapy

Chemotherapy is not a standard treatment for most kidney cancers, as kidney cancer cells are usually resistant to chemotherapy drugs. Some drugs, such as vinblastine, floxuridine, 5-fluorouracil (5-FU), capecitabine and gemcitabine have been shown to help a small percentage of people with renal cell carcinomas. In these cases, chemotherapy is often used only after targeted therapy and/or immunotherapy has already been tried. However, chemotherapy is often the first and best option for some very rare kidney cancers such as renal medullary carcinoma, collecting duct carcinoma, Wilms tumors and malignant rhabdoid tumors.

Combination Treatment Approaches

The following approaches are approved by the FDA for the treatment of kidney cancer:

• A combination of the targeted therapy axitinib and the immunotherapy pembrolizumab.
• Axitinib in combination with the immunotherapy avelumab.
• The immunotherapy nivolumab, in combination with the targeted therapy cabozantinib, for the initial treatment of advanced kidney cancer.
• The targeted therapy lenvatinib plus the immunotherapy pembrolizumab as an initial treatment for advanced kidney cancer.
• Nivolumab and hyaluronidase for the treatment of people with advanced kidney cancer who received prior anti-angiogenic therapy.

All cancer treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and allow you to stick with your treatment plan. It’s important to remember that not all patients experience all side effects, and patients may experience side effects not listed here.

Side Effects of Immunotherapy and Targeted Therapy

Targeted therapy drugs don’t have the same effect on the body as do chemotherapy drugs, but they can still cause side effects. Common side effects of targeted therapy include diarrhea, skin rashes, liver problems (such as hepatitis and elevated liver enzymes), problems with blood clotting and wound healing, and high blood pressure.

Immunotherapy travels through the bloodstream, helping to prompt an immune response. Although immunotherapy drugs are generally fairly well-tolerated, certain side effects may be experienced, including those listed in the “General Side Effects” section. Rare and serious side effects include the development of an inflammation in the lungs or in the colon, causing difficulty breathing or severe diarrhea. These symptoms must be treated immediately.

Another complication of immunotherapy can be extreme fatigue. If this occurs, contact a member of your health care team immediately, so that you can receive immediate medical attention.

General Side Effects

Some side effects may occur across treatment approaches. This section provides tips and guidance on how to manage these side effects should they occur.

Managing Digestive Tract Symptoms 

Nausea and vomiting

• Avoid food with strong odors, as well as overly sweet, greasy, fried or highly seasoned food.
• Eat meals cold or at room temperature, which often makes food more easily tolerated.
• Nibble on dry crackers or toast. These bland foods are easy on the stomach.
• Having something in your stomach when you take medication may help ease nausea.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade that provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.
• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine, contact a member of your health care team.
• Choose foods that contain soluble fiber, like beans, oat cereals and flaxseed, and high-pectin foods such as peaches, apples, oranges, bananas and apricots.
• Avoid foods high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Loss of appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal.
• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.
• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna or trail mix.
• If you are struggling to maintain your appetite, talk to your health care team about whether appetite-building medication could be right for you.

Managing Fatigue 

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are taking a medication, your doctor may lower the dose of the drug, as long as it does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks during the day.
• Take walks or do some light exercise, if possible.
• Try easier or shorter versions of the activities you enjoy.
• Ask your family or friends to help you with tasks you find difficult or tiring.

There are also prescription medications that may help, such as modafinil. Your health care team can provide guidance on whether medication is the right approach for your individual circumstances.

Managing Pain

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the-counter medication to determine if it is safe and will not interfere with your treatments. Many pain medications can lead to constipation, which may make your pain worse. Your doctor can prescribe medications that help to avoid constipation.

Physical therapy, acupuncture and massage may also be of help in managing your pain. Consult with a member of your health care team before beginning any of these activities.

Managing Dehydration

The drugs that are used to treat cancer can make you feel dehydrated. Keeping a water bottle with you is one easy way to help you stay well-hydrated. Hydration can also be provided by liquids other than water, such as Gatorade, juice, soup and fruit smoothies. Be sure to stop taking in fluids early enough in the evening so that your sleep is not disrupted.

Frequently Asked Questions

Q: I’ve heard the term “precision medicine.” What does that mean?

A: Each tumor has its own biological makeup, based on the genes found in its cells. An important area of cancer research is understanding this biology. With this information, it’s possible for doctors to know whether a particular tumor is likely to respond to a specific treatment, allowing them to suggest the right treatment for each person’s tumor. This approach is known as precision (or personalized) medicine.

To better understand the biological makeup of a person’s tumor, doctors look for tumor “markers” in cell genes. Markers can predict whether a given treatment will be effective against a tumor and whether there is a high risk of the tumor coming back. Tumor markers and genetic traits are an important step on the road toward precision medicine, and they are being actively studied in clinical trials for kidney cancer and other types of cancer.

Q: Does kidney cancer run in families?

A: There is research indicating there might be a hereditary component in some cases of kidney cancer. If you have a family history of kidney cancer and have also been diagnosed, or if you were diagnosed with kidney cancer at the age of 50 or younger, you should talk to your doctor about the possibility of meeting with a genetic counselor. It’s important to note that there are many risk factors for kidney cancer not related to heredity, including smoking, obesity and high blood pressure.

Q: Are there any kidney cancer treatments that have been granted the Fast Track designation by the FDA?

A: The FDA’s Fast Track program facilitates the development and expedites the review of drugs to treat serious conditions. The purpose is to get important new drugs to the patient earlier. The FDA has granted Fast Track designation to the following investigational drugs:

• Batiraxcept, for the treatment of clear cell kidney cancer that progressed following systemic therapy. Batiraxcept is a protein that binds to another protein called GAS6, inhibiting tumor growth.
• ADI-270, for the treatment renal cell carcinoma, the most common type of renal (kidney) cancer. ADI-270 is a CAR T-cell therapy, a type of immunotherapy.
• IVS-3001, a CAR T-cell therapy, for previously treated HLA-G–positive locally advanced or metastatic clear cell renal cell carcinoma.