Advanced Renal Cell Carcinoma (Kidney Cancer): Treatment Options and the Latest Advances

Clear cell renal cell carcinoma is the most common type of kidney cancer. Nonclear cell renal cell carcinoma accounts for about 20% of all kidney cancer. Unlike some other types of cancer, most people who develop renal cell carcinoma don’t experience any symptoms. This means that sometimes people aren’t diagnosed with renal cell carcinoma until the cancer has spread to other parts of the body. This is called advanced renal cell carcinoma. 

Other times, people find out they have renal cell carcinoma while the cancer is still only in the kidney. In some cases, the cancer returns despite treatment. Relapsed (or returned) renal cell carcinoma is another type of advanced renal cell carcinoma.

Advanced renal cell carcinoma is more difficult to treat but that doesn’t mean there isn’t hope. There are new medications that treat this type of cancer. These breakthrough medications can help people live longer and have fewer side effects than some other types of cancer treatment. Let’s take a look at the options for treating advanced renal cell carcinoma. 

What are the treatment options for advanced renal cell carcinoma? 

Advanced renal cell carcinoma is usually treated with systemic therapy. These are medications that are given by mouth or via an IV. They work by targeting cancer cells in different ways. The goal is to find cancer cells and stop them from growing. 

There are two main types of systemic therapy: targeted therapy and immunotherapy. Chemotherapy, which can treat other types of cancer, doesn’t work well for clear cell and most nonclear cell renal carcinomas. So chemotherapy isn’t a common treatment option for these kidney cancers.  

Instead, people receive targeted therapy and immunotherapy, either together or alone. The exact treatment plan and combination will be different from person to person depending on their specific situations. 

Keep in mind that there are different types of renal cell carcinoma. Clear cell renal cell carcinoma is the most common type. These approaches work best for clear cell renal carcinoma but may also work for nonclear types of this cancer, too. 

The goal of systemic therapy is to get people to remission. If remission lasts a long time, particularly even after treatment is stopped, some people can be cured even if they have advanced kidney cancer. If a cure isn’t possible, targeted therapy can still prolong remission and help people live longer.

Targeted therapy

Targeted therapy can be used to treat stage 4 or relapsed renal cell carcinoma. They block proteins or chemicals that allow cancer cells to grow by blocking a key protein made by clear cell kidney cancer called vascular endothelial growth factor (VEGF). There are the two main types of targeted therapy:

• Monoclonal antibodies: There are many types of monoclonal antibodies. The ones that fall under this category prevent blood vessel growth by blocking VEGF. This “starves” tumors so they can’t grow and spread.

• Kinase inhibitors: These include tyrosine kinase inhibitors that block the receptors for VEGF in the cancer, and mTOR inhibitors. mTOR and VEGF receptor inhibitors block signals inside the cancer cell so they cannot grow and can slow the blood vessel growth around the cancer. 

Immunotherapy

Immunotherapy is the other type of systemic therapy that treats advanced renal cell carcinoma. Immunotherapy works by boosting your immune system. Normally, immune cells fight off cancer cells, but this process is tightly controlled by your body because of proteins called immune checkpoints. These checkpoints shield the cancer from the immune system. By blocking a checkpoint, immunotherapy helps the immune system bypass these controls. 

Immunotherapy can treat relapsed or stage 4 renal cell carcinoma. It can be given alone or with targeted therapy. 

There are two main types of immunotherapy:

• Monoclonal antibodies: These monoclonal antibodies aren't the same as the ones that are part of targeted therapy. Though both are made in a lab, they work differently. These monoclonal antibodies block the immune checkpoint proteins that control the immune system’s response to cancer. They’re called immune checkpoint inhibitors. People usually receive two immune checkpoint inhibitors at the same time because the medications work better when given together, according to research. Some immune checkpoint inhibitors can also be given with a kinase inhibitor since these treatments attack cancer in different ways. It’s not known which of these approaches works best, but all approaches have shown improved outcomes when compared with older treatments for kidney cancer.

• Cytokine therapy: These medications boost a protein that plays an important role in the immune system. This treatment is called high-dose interleukin-2 and was used in the past before immune checkpoint inhibitors were developed. Cytokine therapy isn’t used to treat advanced kidney cancer very often. 

Surgery

Most people with advanced renal cell carcinoma can’t be treated with surgery. Usually the cancer has spread too much for surgery to help. 

But in some cases, people may benefit from cytoreductive nephrectomy. This procedure removes the tumor inside the kidney and works best if people have a large tumor and only a small amount of metastases. Studies are looking at who should be offered a cytoreductive nephrectomy.

Surgery can also remove large areas of metastases that can relieve pain and discomfort or when there are only a few number of metastases. 

In some cases, this type of surgery can help people avoid systemic therapy. In some cases, people with advanced renal cell cancer can even be cured with surgery alone. But most people who receive surgery also will need treatment with systemic therapy if they have advanced kidney cancer with metastasis. 

Radiation therapy

Like surgery, radiation therapy can’t treat advanced renal cell carcinoma on its own. But it can be helpful to relieve pain from bone or brain metastasis. Radiation therapy works by using energy from radiation to shrink or kill cancer cells.

People can receive radiation therapy along with systemic therapy to treat advanced renal cell carcinoma.

How are systemic therapies used together to treat advanced renal cell carcinoma?

Targeted therapies and immunotherapies may be used together or alone to treat advanced renal cell carcinoma. Since each type of therapy works in a different way, putting them together gives people a better chance at fighting off cancer. Some people also take two immunotherapies at the same time.

There’s a dizzying array of medications in each of these categories. Here’s a chart that can help you keep track:

What new treatment options are being developed for advanced renal cell carcinoma?

New breakthroughs in treatment are helping people with kidney cancer live longer, fuller lives. New treatments are tested in clinical trials before becoming available to everyone. 

For some people with advanced renal cell carcinoma, a clinical trial is the best first step in treatment. You can find out more about what clinical trials are available using the Kidney Cancer Association’s clinical trial finder tool.

You can also connect with the Kidney Cancer Association’s patient navigator by phone or email. These experts can tell you more about emerging treatments and how to get access to clinical trials.

What is the prognosis for advanced renal cell carcinoma?

Right now, the estimated 5-year survival rate ranges from 15% to 72%. In cases where the cancer has only spread to nearby body parts, people have a higher 5-year survival rate. But people with more widespread cancer have lower survival rates.  

But keep in mind that the prognosis for advanced renal cell carcinoma is changing. These numbers are updated every 5 years. They don’t yet reflect the complete effect of targeted therapies and immunotherapy. As time goes on, these numbers may continue to get better. 

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Written by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

Reviewed by:

Andrew J. Armstrong, MD, ScM

Andrew J. Armstrong, MD, ScM, is a tenured professor of medicine, surgery, pharmacology, and cancer biology and director of research for Duke Cancer Institute’s Center for Prostate and Urologic Cancers.

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