Stage 4 Renal Cell Carcinoma: Treatment and Prognosis

Although stage 4 RCC is classified as an advanced stage of cancer, there are still treatment options available.

Surgery

In some cases, when the main tumor is removable and the cancer has not spread extensively, a radical nephrectomy may be performed. This involves surgically removing most or all of the affected kidney.

Surgical removal of other tumors may be needed for people with metastatic cancer. A team of specialists will decide whether the metastasized tumors can be removed without too much risk.

If surgery isn’t possible, tumor embolization may be used. This procedure cuts off the blood supply to the tumor, which helps to reduce symptoms.

Once surgery has been performed to remove local tumors, many people may need systemic therapy. This type of therapy treats cancer throughout the body. It can help to reduce cancer recurrences.

Systemic therapy for stage 4 RCC includes immunotherapy, targeted therapy, radiation, and chemotherapy.

Immunotherapy

Immunotherapy is a treatment technique that aims to stimulate the immune system to attack cancer cells. Not everyone with RCC responds well to immunotherapy, and side effects can be serious.

Immunotherapy, or biologic therapy, is a treatment that helps your immune system attack the cancer. It is often introduced when the RCC cannot be removed with surgery.

Immunotherapy uses a few different types of drugs:

Checkpoint inhibitors

Your immune system uses a system of “checkpoints” to differentiate between healthy and cancerous cells. Checkpoint inhibitors aim to help your immune system find cancer cells that are hiding from your immune system.

Nivolumab (Opdivo) is a checkpoint inhibitor administered through an IV that has become more commonly used in RCC treatment in recent years.

Side effects include:

• rash
• fatigue
• diarrhea
• nausea
• headache
• skin rash
• joint pain
• abdominal pain
• trouble breathing

Interleukin-2

Interleukin-2 (IL-2, Proleukin) is an artificial copy of proteins called cytokines that aim to activate your immune system to attack the tumor cells.

It’s shown to have the potential to cure the disease in certain people. It can have serious side effects so is only used in healthy individuals who are more likely to tolerate the side effects.

One 2017 study of effectiveness on predominantly white men with an aggressive form of RCC did see a higher survival rate with the use of high-dose interleukin-2.

Side effects include:

• fatigue
• bleeding
• chills
• fever
• low blood pressure
• fluid in the lungs
• kidney damage

Interferon alpha

Interferons have antiviral, antiproliferative (inhibits cancer cell growth), and immunomodulatory (affects the body’s immune system) properties. Interferon alpha aims to stop tumor cells from dividing and growing.

Interferon is sometimes given with other drugs, such as bevacizumab (Avastin).

Side effects of interferon include:

• nausea
• flu-like symptoms
• fatigue

Interferons have been mostly replaced by single-agent targeted therapy. Single-agent interferon therapy is typically no longer used.

Targeted therapy

Targeted therapy for RCC means using drugs that specifically target cancer cells. Targeted drugs are desirable because they don’t harm or kill healthy cells in the body.

There are several targeted medications for stage 4 RCC that work to inhibit cell growth. They target a protein called vascular endothelial growth factor (VEGF) that stimulates the growth of cancer cells.

The development of these targeted drugs has helped extend the lives of some stage 4 patients. The treatment has proven promising enough that researchers continue to develop new targeted drugs.

The drug bevacizumab (Avastin) blocks VEGF and is administered through a vein.

Side effects include:

• diarrhea
• weight loss
• fainting
• appetite loss
• heartburn
• mouth sores

A tyrosine kinase inhibitor (TKI) stops new blood vessel growth in tumors and comes in pill form. Examples of this type of drug include:

• sorafenib (Nexavar)
• cabozantinib (Cabometyx)
• pazopanib (Votrient)
• sunitinib (Sutent)

Side effects of TKIs include:

• high blood pressure
• nausea
• diarrhea
• pain in your hands and feet

mTOR inhibitors

Mechanistic target of rapamycin (mTOR) inhibitors target the mTOR protein, which encourages renal cell cancer growth.

These include:

• temsirolimus (Torisel), administered through an IV
• everolimus (Afinitor), taken orally in pill form

Side effects include:

• rash
• weakness
• appetite loss
• mouth sores
• fluid buildup in the face or legs
• high blood sugar and cholesterol

Radiation therapy

Radiation uses high-energy X-ray beams to kill cancer cells. Radiation can also be used after surgery to kill any cancer cells left behind after treatment.

In advanced RCC, it’s often used to relieve symptoms like pain or swelling. This kind of treatment is called palliative care.

Side effects of radiation include:

• stomach upset
• skin redness
• fatigue
• diarrhea

Chemotherapy

Chemotherapy is a traditional treatment method for several types of cancers. It involves using a drug or combination of drugs to kill cancer cells.

Chemotherapy drugs aren’t targeted, however, so they kill healthy cells as well and produce a lot of side effects.

Chemotherapy often doesn’t work well on people with RCC. However, your doctor could recommend it if immunotherapy and targeted treatments haven’t worked.

This treatment is either taken intravenously or in pill form. It is given in cycles with intermittent periods of rest. You typically need to receive chemotherapy every month or every few months.

Side effects include:

• fatigue
• mouth sores
• nausea and vomiting
• diarrhea or constipation
• hair loss
• appetite loss
• increased risk for infections

Another option for people with stage 4 RCC is to become involved in clinical trials. Clinical trials are research trials for testing new drugs and treatments.

You can discuss current clinical trials — as well as their potential risks and benefits — with your doctor or healthcare provider.

Doctors who diagnose and treat RCC and other types of cancer use a staging system. Each person with RCC is given a number designation ranging from 1 to 4. Stage 1 is the earliest stage of the disease and stage 4 is the latest and most advanced.

Staging for RCC is based on:

• size of the primary tumor in the kidney
• spread of cancerous cells from the primary tumor to nearby tissues
• degree of metastasis
• spread of the cancer to other organs in the body

Stage 4 RCC can include different combinations of staging criteria:

• When the primary tumor is large and has spread throughout the kidney and into nearby tissues. In this instance, the cancer cells may or may not have spread into other organs in the body.
• When the cancer has metastasized and is present in distant organs. In this case, the primary tumor may be of any size, and there may or may not be any cancer in the tissues immediately surrounding the kidney.

The 5-year relative survival rate for people with stage 4 RCC is 12 percent. However, different scenarios may result in higher survival rates.

People who are able to have surgery to remove metastatic tumors have better survival rates, and many who are treated with targeted drugs survive longer than those who don’t.