Understanding Treatments for Metastatic Renal Carcinoma

Advanced kidney cancer is serious stuff, but you have options. Learn more about the best way forward.

by Jeanine Barone Health Writer

You’re probably reeling after learning that you have metastatic kidney disease. This diagnosis might even have you thinking there’s little you can do to fight the spread of this cancer. In fact, though, the field is rapidly changing, providing more treatment options than ever before. We’re here to help guide you through the various treatments available for advanced kidney cancer, including what’s most-often recommended, for whom, and how they work.

What Is Advanced Kidney Cancer?

Let’s start with the basics: Renal cell carcinoma, the most common form of kidney cancer, grows within the kidney, but it can spread beyond the kidney itself. If the cancer spreads, it’s referred to as stage IV kidney cancer or metastatic kidney cancer. Kidney cancer can spread both near and far, from the adrenal gland that sits atop the kidney to the lymph nodes that are scattered around the body. The most common sites for the tumor to spread include the bones, lungs, and brain. It’s scary stuff, for sure, but there are several different routes to treating advanced kidney cancer. The path you take will be something you’ll discuss with your doctor.

“When a patient has metastatic kidney cancer, we review multiple factors to determine the best treatment options,” says Jorge A. Garcia, M.D., an assistant professor at the Case Western Reserve University School of Medicine and chief of solid tumor oncology, based in Cleveland, OH. These factors include where the cancer has spread, whether you have other health conditions, and what medications you’re taking. For example, you’ll want to tell your physician if you have an autoimmune condition, such as celiac disease or multiple sclerosis; if you’ve had an organ transplant; or if you’re taking a steroid or other medications that affect the immune system, says Sandy T. Liu, M.D., assistant professor, hematology-oncology at the David Geffen School of Medicine at UCLA in Los Angeles. All of these variables can reduce the likelihood that you’re a good candidate for immunotherapy, a broad category of drugs used to treat metastatic kidney cancer.

When Is Surgery an Option?

“While not common, there are some instances where surgery may be recommended for patients with metastatic kidney cancer,” says Randy F. Sweis, M.D., assistant professor of medicine at University of Chicago Medicine. One instance is when just a few tumors have spread and they can be readily removed with the goal of eradicating the cancer or at least prolonging the time until you’ll need further treatment, says Dr. Sweis. Another instance is when there is a tumor causing pain or other problems, such as bleeding or damage to a bone.

“The decision for surgery in patients with metastatic kidney cancer requires a close discussion between the patient, medical oncologist, and surgeon,” says Moshe Ornstein, M.D., a kidney cancer medical oncologist at the Cleveland Clinic. In some cases where the cancer has spread to only a few body parts, Dr. Ornstein will first treat with immunotherapy for a few months and then determine (via computed tomography—CT scans) if the tumor has shrunk. “[I can then] reconsider whether surgery is appropriate. This way I am not unnecessarily sending a patient to surgery right away but at the same time not taking it off the table.”

Medication Options: What Are Targeted Therapies?

There are two general types of medications doctors use to curtail or slow the growth of cancer cells or reduce the size of tumors. One is a category called targeted therapies. Most are given as pills, and they focus on (or target) specific proteins or other molecules found on the surface of or inside the cancer cell in order to battle the cancer. There are two main categories of targeted therapies: VEGF inhibitors (vascular endothelial growth factor) and mTOR (mammalian target of rapamycin) inhibitors. According to Dr. Liu: “VEGF inhibitors are the workhorse for kidney cancer treatment.” These drugs (such as cabozantinib and sunitinib) work by preventing blood vessels in and around the tumor from growing—something that’s necessary for cancer cells to multiply. Some of the most-common side effects include diarrhea, headaches, hair loss, numbness, or a stuffy nose.

The mTOR inhibitors are drugs (such as everolimus and temsirolimus) that work by hampering a protein needed for tumor cells to grow and divide. However, “mTOR monotherapy [a.k.a. taken alone and not in combination with another drug] is less effective than a VEGF inhibitor,” says Dr. Liu. Your doctor might prescribe this as a second line of treatment when other drugs aren’t working. Side effects include mouth sores, loss of appetite, fatigue, swelling in the arms or legs, or breathing problems.

Medication Options: How Can Immunotherapy Help?

Besides the targeted therapies we just covered, the other first-line treatment most-often used to treat advanced kidney cancer is an immunotherapy known as checkpoint inhibitors. Checkpoint inhibitors (such as nivolumab and pembrolizumab) block the “checkpoints”—specific proteins found on the surface of T cells (a type of immune cell). (Normally, when the T cell binds to a healthy cell, the checkpoint proteins allow the T cell to recognize it as “self” and, therefore, it doesn’t attack. But cancer cells can trick the immune system into accepting them as healthy cells.) With checkpoint inhibitors, when the T cell encounters the cancer cell, the checkpoint proteins are shut off, allowing the immune system to recognize the cancer cells as “foreign” and then destroy them. The side effects of checkpoint inhibitors include skin rash, joint pain, fatigue, or fever.

Medication Options: What Is Combination Therapy?

If your doctor is treating your disease with medication, it’s most likely going to be a combination of targeted therapies and immunotherapy, and it’s just what it sounds like: two different drugs prescribed at the same time. It may be a combo of two immunotherapy drugs or a combo of one immunotherapy drug with one targeted-therapy drug. Doctors like this technique because when the drugs work together, they often improve survival rates.

According to Dr. Liu: “Combination immunotherapy is the mainstay to treat kidney cancer in 2021.” She adds that the backbone of this treatment is PD-1 immunotherapy (such as nivolumab or pembrolizumab), a checkpoint inhibitor, where, for example, nivolumab can be combined with another checkpoint inhibitor (such as ipilimumab) or pembrolizumab can be combined with axitinib, a targeted therapy. (Some of the drugs used in combination therapy are pills while others require an infusion into a vein). However, combination therapy can come with a greater array and degree of side effects, so physicians may offer combination therapy to those people who are otherwise healthy.

How Do I Manage Medication Side Effects?

It’s all about keeping an open line of communication with your doctor. Dr. Liu says that having your doctor explain the potential side effects up front allows you to be on the lookout so that if they happen, you can immediately let your doctor know. There are many ways to deal with side effects, including reducing the dose, putting the drug on a temporary pause, or use other drugs to manage immune-related side effects.

Dr. Liu adds: “It is also important to have a multi-disciplinary team that specializes in immune-related side effects [since] they can be very challenging to manage.” So in addition to your oncologist—your lead cancer doc and the expert when it comes to managing severe immune side effects—you might also have input from MDs who specialize in immunology, dermatology, infectious disease, and other subspecialties to help your oncologist treat your side effects.

What About Radiation Therapy?

Radiation therapy, a.k.a. radiotherapy, involves targeting the tumors that spread with high doses of X-rays, which kill the cancer cells. Typically, this procedure is done if the tumors are small and have not spread to many places in the body, nor can they be removed by surgery.

Typically, a machine outside the body focuses the radiation on the tumor site, reducing damage to the surrounding tissues. “Radiation is [typically] used for brain and bone metastasis,” says Subodh Regmi, M.D., a urologist with the University of Minnesota Medical School and M Health Fairview in Minneapolis. The side effects include hair loss, nausea, fatigue, or skin redness.

... and Ablation Therapy?

Ablation is a treatment that avoids damage to the surrounding tissues. It involves using either extreme cold (such as with liquid nitrogen) or heat (generated by the energy waves of radiofrequency)—typically delivered by a probe or a needle through the skin—to destroy the tumors. Ablation therapy can be used in parts of the body, like the bone, where surgery can’t be done to remove the tumor, says Dr. Regmi. Side effects may include pain and bleeding.

Bottom Line

Any time cancer spreads, it’s scary and advanced kidney cancer is no exception. The key is to get informed about the range of treatments available and to consider the options that might be right for your particular disease. And that means having an ongoing, open dialog with your doctor and asking all your questions—big and small. From an array of medication options to surgery, radiation or ablation, your outlook with advanced kidney cancer has never been better.

Jeanine Barone
Meet Our Writer
Jeanine Barone

Jeanine Barone is a scientist and journalist with an eclectic background. She’s a nutritionist and exercise physiologist who regularly writes about travel, health, fitness, and food for numerous top-tier publications. Jeanine enjoys active travel, especially long-distance cycling and cross-country skiing.