Let's Talk About Metastatic Kidney Cancer
When cancer spreads beyond the kidney, treating this disease becomes more challenging, but not hopeless. Learn how new medications are changing the game.
Finding out that you have kidney cancer is scary. Learning it has spread beyond your kidney—that’s even worse. But metastatic kidney cancer is not a death sentence. Radiation therapy and surgery can offer relief from some of the most debilitating symptoms of advanced kidney cancer, while new medications that stave off disease progression are helping people live longer, with fewer side effects. We have the rundown on what it means to have metastatic kidney cancer, and the latest treatment options available.
Our Pro Panel
We went to some of the nation's top experts in kidney cancer to bring you the most up-to-date information possible.
Pedro Barata, M.D.
Tulane Cancer Center
New Orleans, LA
Katy Beckerman, M.D, Ph.D.
Vanderbilt University Medical Center
Pavlos Msaouel, M.D., Ph.D.
The University of Texas MD Anderson Cancer Center
While anyone can get kidney cancer, more than 90% of patients get diagnosed with renal cell carcinoma when they’re over 45, and almost half when they’re over 65. Men are nearly twice as likely as women to develop the disease. The type of kidney cancer is often the best indicator of how quickly the cancer can spread, but any form of kidney cancer has the potential to develop in different areas of the body.
It’s rare for patients to be completely disease free after treatment, but not unheard of, although there’s always a chance that the disease can come back. Less than 5% of patients show no evidence of disease after targeted therapies, and almost 10% of patients show a complete response to a certain combination of immunotherapies, while between 4% and 6% are disease free after treatment with a mix of immunotherapies and targeted therapies.
To progress to stage 4 kidney cancer, cancer cells travel through the blood or lymphatic system (part of the immune system) to other areas of the body. Most often, they appear as new tumors in the lungs, bone, liver, and brain, but they can show up almost anywhere.
Doctors often recommend clinical trials for patients who don’t have clear cell renal cell carcinoma, like papillary or chromophobe RCC. If you are enrolled in a trial, you might receive the standard treatment or be part of the first wave of patients to try a new therapy.
What Is Kidney Cancer, Again?
Behind your gut sit two potato-shaped organs that filter your blood, make pee, and keep your blood pressure and red blood cell count in check—these are your kidneys. If a solid mass forms inside these organs, then grows and spreads, it’s called a cancerous tumor. When tumors develop in the pipelines of the kidney that filter blood, the cancer is called a renal cell carcinoma (RCC), and that’s what this guide will focus on.
There are a bunch of different renal cell carcinomas, depending on what the cancer cells look like under a microscope. The most common variety is called clear cell renal cell carcinoma (you might have guessed: its cells look clear), which shows up in about three-quarters of renal cell carcinoma patients.
Besides knowing what type of kidney cancer you have (once you’ve had a biopsy or surgery), you’ll also find out how far the cancer has progressed, or the cancer stage (I through IV). When cancer cells spread and form tumors outside of the kidney, that’s called metastasis, and is considered stage IV (also 4), or advanced kidney cancer.
How Common Is Metastatic Kidney Cancer?
Nearly a third of people with renal cell carcinoma have already reached stage 4 cancer by the time they are diagnosed—kidney cancer symptoms are notoriously invisible, so many people don’t realize they have it until the advanced stages. And in those with earlier stages of kidney cancer, metastatic cancer reappears in about one in four cases, usually in the first three years after initial treatment.
Renal cell carcinoma that has reached the stage of metastatic cancer spreads through the blood or lymphatic system (a network of lymph nodes that runs throughout the body, part of the immune system), so tumors can pop up almost anywhere. Here’s where kidney cancer travels most often:
Lungs (in almost half of people with metastatic disease).
Bone (in about a third of patients)
Lymph nodes (about one in five patients)
Liver (about one in five patients)
Adrenal glands (nearly one in ten patients)
Brain (in close to 8% of patients)
When tumors reach these regions, people often have corresponding symptoms, like trouble breathing, bone pain, or neurologic issues.
Treatment Options for Metastatic Kidney Cancer
If cancer has spread beyond the kidneys, medications (also called systemic therapy) are the mainstay treatment, but people can also benefit from radiation therapy and surgery. Before we dive into the pharmaceutical options, here’s an overview of those other treatments.
About a third of patients with metastatic kidney cancer receive radiation, which uses high energy waves to kill cancer cells, either through a machine outside the body (called external-beam radiation therapy) or by being placed directly into a tumor with a needle or catheter.
This doesn’t get rid of a tumor, but can help relieve symptoms like pain and bleeding, and is most commonly used when cancer has spread to the bones or brain. The side effects of radiation range but can leave your skin with the feeling of a bad sunburn, and cause nausea, diarrhea, and fatigue.
It’s not a cure, but surgery to remove some or all of a kidney (a nephrectomy) can extend the life of patients with advanced kidney cancer over a few months, according to a number of studies, and can help manage symptoms of the disease. Keep in mind, this is only an option when patients are healthy enough to undergo an invasive medical procedure.
Drug Therapy for Metastatic Kidney Cancer
The last 15 years have seen a dramatic surge in medications to treat advanced kidney cancer, from just two (quite toxic) drugs that were only effective in a small percentage of patients, to over a dozen meds that combat cancer cells in different ways, often used in combination.
While for some patients, certain medications appear to get rid of cancer cells altogether, this type of response is rare. More often, people take these medicines until their cancer starts to progress again, then doctors switch to different therapies.
Since most of these meds are still so new, they haven’t all been compared to one other. There are a number of options for the first choice of medications and order to try. These decisions often depend on conversations between you and your doctor. But researchers are continuously learning more about how these drugs affect different people in clinical trials.
It’s important to realize that nearly every medication for kidney cancer has been tested to treat clear cell renal cell carcinoma—the most common kidney cancer—and some, but certainly not all, have also shown to be effective in treating other types of cancer as well. If you have a less common renal cell carcinoma, doctors recommend seeing a specialist who has experience treating rare kidney cancers.
How Do Cancer Drugs Work?
The medications out there are split into two groups: immunotherapies (or biologic therapy) and targeted therapies. Often these two types of drugs are used together. Here’s a deeper dive into individual medications.
Immunotherapies (Biologic Therapy)
These treatments ramp up the body’s immune system to fight cancer cells, and can be broken into three major approaches:
Immune Checkpoint Inhibitors
One of the reasons that cancer is so hard to treat is that cancer cells doing a frustratingly good job of hiding from the systems in the body that are supposed to detect and kill them. That’s because cancer cells are covered with the same proteins (called checkpoints) that are found on other cells in your immune system, called T cells. T cells are supposed to act as the body’s army against outside invaders, but imagine going to battle against a sea of soldiers who are all wearing the same armor. Which ones do you shoot? T cells have a hard time battling cancer cells when they are wearing their “disguise.”
This new class of drugs, usually given by infusion, works by outwitting the cancer cells, blocking their ability to make checkpoint proteins (hence the name checkpoint inhibitors), and thereby exposing the cancer cells to T-cell attack. Here’s what’s available:
Bavencio (avelumab): This is approved for use along with a targeted therapy called axitinib as a go-to choice (or first line therapy).
Keytruda (pembrolizumab): This is also approved in conjunction with axitinib as a first line therapy.
Opdivo (nivolumab): Approved as a first line therapy for patients with certain risk factors, in conjunction with ipilimumab.
Yervoy (ipilimumab): Approved in conjunction with nivolumab.
Your immune system naturally produces these proteins that slow tumor growth. This biologic treatment was one of the only medications available in the past, but it’s now only used in conjunction with a targeted therapy called bevacizumab for maximum efficacy.
Interferon Alfa (IFN-alpha): given by injection.
This type of drug was also one of the earliest options for treating advanced kidney cancer but is no longer a primary treatment option. It works by telling your body to produce certain white blood cells called lymphocytes that attack cancer cells. But only about 10% of patients respond to this drug at high doses, and it can cause life-threatening complications (called capillary leak syndrome). Doctors recommend that the treatment is only used at experienced cancer centers.
Proleukin (aldesleukin): given by IV
Side Effects of Biologic Therapies
Since these drugs stimulate the immune system, they can cause a wide range of side effects, ranging from rashes to fever, fatigue, heart disease, diarrhea, and shortness of breath.
These drugs make use of how cancer cells function to limit their spread, either by stopping blood vessels from growing in a tumor (called angiogenesis) or limiting certain proteins called tyrosine kinases that keep cancer cells alive. These are the major targeted therapies used for metastatic kidney cancer:
Cancer cells produce a protein called vascular endothelial growth factor, or VEGF, that encourages blood vessels to form, spurring tumor growth. (Normal cells also produce this protein, but in smaller amounts.) These drugs block the blood vessel growth, starving a tumor of nutrients.
Avastin or Mvasi (bevacizumab): Given by IV, this is approved as a first line treatment, given with Interferon.
Cabometyx or Cometriq (cabozantinib): Another first line treatment.
Inlyta (axitinib): This is only approved for patients who haven’t improved with other treatments.
Lenvima (lenvatinib): Approved for use with everolimus, this drug is only for patients who haven’t improved with other treatments.
Nexavar (sorafenib): Approved as a first line treatment.
Sutent (sunitinib): Approved as a first line treatment.
Votrient (pazopanib): This is approved as a first line treatment that has fewer side effects than sunitinib in many patients, but may impair liver function.
mTOR is a protein that helps control cell division and is often more active in cancer cells than normal cells. Aptly named, mTOR inhibitors block this protein to halt cancer cell growth.
Afinitor, Afinitor Disperz, or Zortress (everolimus): These drugs are only approved for patients who haven’t improved with other treatments.
Torisel (temsirolimus): Given by IV; this is only approved as a first-line treatment for patients with a number of risk factors that show the disease is progressing.
Side Effects of Targeted Therapies
These drugs come with a range of side effects, including nausea, diarrhea, high blood pressure, vomiting, fatigue and weakness, and other, more serious, symptoms.
What’s the Prognosis for Advanced Kidney Cancer?
Overall, about 13% of patients with metastatic kidney disease survive for five years after their diagnosis, according to the most recent figures. Researchers have also found a number of risk factors that can help predict your chance of survival with advanced kidney disease, including how quickly you require systemic treatment after your diagnosis, as well as certain markers in your blood for:
Neutrophils (a type of white blood cell)
Keep in mind that although 13% is a low number, many treatments are so new that their success is not yet captured in the data. Also, survival rates refer to an average outcome of a large group—it can’t tell you about your disease and response to treatment.
While it’s not the norm, some metastatic patients remain disease-free after treatment with certain medications, though doctors still don’t fully understand why these drugs beat off cancer in some people and not others.
The bottom line: Statistics are just that—averages of many people, none of whom have your unique situation (or your unique kick-ass willpower). While statistics can help guide your doctors in what treatments to try, it can’t tell them—or anyone—how your story will unfold. You can still play a role in shaping your future by making healthy choices and thinking positive thoughts. Go ahead, we’re right here with you.
- FDA-Approved Drugs for Advanced Disease: National Cancer Institute. (2020). “Drugs Approved for Kidney (Renal Cell) Cancer.” cancer.gov/about-cancer/treatment/drugs/kidney
- Treatment Guidelines (1): American Urological Association (2017). “Renal Mass and Localized Renal Cancer: AUA Guideline.” auanet.org/guidelines/renal-cancer-renal-mass-and-localized-renal-cancer-guideline
- Treatment Guidelines (2): (2017). National Comprehensive Cancer Network. “Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.” jnccn.org/view/journals/jnccn/15/6/article-p804.xml
- Surgery for Advanced Disease: Tumori Journal. (2017). “Treatment of Advanced Renal Cell Carcinoma: Recent Advances and Current Role of Immunotherapy, Surgery, and Cryotherapy.” ncbi.nlm.nih.gov/pubmed/27791232
- Systemic Therapy: New England Journal of Medicine. (2017). “Systemic Therapy for Metastatic Renal-Cell Carcinoma.” nejm.org/doi/full/10.1056/NEJMra1601333
- Overview of Available Medications: Japanese Journal of Clinical Oncology. (2019). “Overview of current and future systemic therapy for metastatic renal cell carcinoma.” ncbi.nlm.nih.gov/pubmed/30722031
- Recent Changes in Clinical Practice: European Urology. (2019). “European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update.” ncbi.nlm.nih.gov/pubmed/30803729
- First Line Treatments: Cancer Treatment Reviews. (2018). “Current and Emerging Therapies for First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma.” ncbi.nlm.nih.gov/pubmed/30173085
- Response to Immunotherapies: New England Journal of Medicine. (2018). “Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma.” nejm.org/doi/10.1056/NEJMoa1712126?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov
- How Different Medications Work: National Cancer Institute. (2020). “Renal Cell Cancer Treatment” cancer.gov/types/kidney/patient/kidney-treatment-pdq#_1
- Risk Factors: International Metastatic RCC Database Consortium. (2020). “IMDC Risk Model for Metastatic Renal Cell Carcinoma.” mdcalc.com/imdc-international-metastatic-rcc-database-consortium-risk-model-metastatic-renal-cell-carcinoma
- Individual Response to Treatment: Nature Reviews Clinical Oncology. (2019). “Towards individualized therapy for metastatic renal cell carcinoma.” ncbi.nlm.nih.gov/pubmed/30992569
- Drug Resistance: Urological Oncology. (2017). “Strategies to Overcome Therapeutic Resistance in Renal Cell Carcinoma.” ncbi.nlm.nih.gov/pmc/articles/PMC5318278/