Metastatic kidney cancer, also called stage 4 kidney cancer, means the cancer has spread beyond the kidneys to other parts of the body.

About 1 in 3 people already have metastatic disease when they are diagnosed with kidney cancer. Another 30 percent of those diagnosed at an earlier stage will later develop metastases.

This article explains the symptoms of metastatic kidney cancer and what to watch for as it spreads. We’ll also discuss your treatment options and when doctors might recommend each.

Symptoms of Metastatic Kidney Cancer

Metastatic kidney cancer symptoms depend mostly on where the cancer has spread. Only about half of people have symptoms from their kidney tumors. Signs and symptoms to look out for include:

• Blood in your urine (pee), which can turn it pink or red
• Unintentional weight loss
• Loss of appetite
• Swelling in your feet and legs
• Fever
• Swollen or enlarged lymph nodes

Some people also develop paraneoplastic syndromes. These can cause high blood pressure, anemia (low red blood cell count), high calcium levels, abnormal liver function test results, and problems with the nervous system, skin, muscles, joints, or hormones.

Metastasis to the Lungs

The lungs are the most common site of kidney cancer metastasis. You may not notice any signs of lung metastases at first.

Sometimes, doctors find the spread on imaging tests done to check other parts of the body. Over time, tumor growth in the lungs can cause:

• Coughing with or without blood
• Shortness of breath
• Chest pain
• Loss of appetite, which can lead to weight loss
• Fluid buildup around the lungs, which can make shortness of breath worse

Metastasis to the Bones

Metastatic kidney cancer often spreads to the bones. Between 20 percent and 35 percent of people with advanced RCC develop bone metastases.

Bone pain is typically the first sign of cancer spread. According to Moffitt Cancer Center, bone metastases tend to form in the:

• Spine
• Skull
• Hip bones in the pelvis
• Femur, the long bone in the thigh
• Ribs
• Humerus, the long bone in the upper arm

Cancer that spreads to the bones can greatly affect daily life. Tumors can weaken the bones and raise the risk of breaks or fractures. Bone pain can be hard to manage, especially if it gets worse when you move or walk.

Tumors in the spine can put pressure on the spinal cord or the nerves at the base of the spine. This pressure may lead to tingling, muscle weakness, pain, and loss of bowel or bladder control.

Metastasis to the Brain

Metastatic kidney cancer spreads to the brain in 4 percent to 11 percent of cases. Renal cell carcinoma (RCC) is the most common type of kidney cancer.

RCC tends to cause brain metastases more often than other kidney cancer types. Clear cell renal cell carcinoma is an aggressive form of RCC that also spreads to the brain.

Brain tumors can cause different symptoms depending on their size and location. People with metastatic kidney cancer to the brain may develop:

• Headaches, usually caused by the tumor pressing on brain tissue
• Loss of coordination and balance problems
• Muscle weakness
• Problems with memory, speech, and sensation

Metastasis to the Adrenal Glands

Your adrenal glands sit on top of your kidneys. They make hormones that help control blood pressure, stress, and metabolism. In some cases, kidney cancer can spread to your adrenal glands.

Adrenal tumors usually don’t cause any symptoms. In fact, they’re often found accidentally on imaging tests for other health issues.

Small case reports have looked at cases of metastatic kidney cancer spreading to the adrenal glands. If the adrenal glands don’t work as they should, you may need hormone replacement.

Treatment options include systemic therapy for the kidney cancer or surgical removal of the adrenal metastasis in some cases.

Metastatic Kidney Cancer Treatment Options

Metastatic kidney cancer treatment mainly uses systemic therapies like immunotherapy and targeted therapies. These medications travel through the bloodstream to kill cancer cells. In some cases, surgery and radiation therapy may be useful.

You and your doctor will work together to find the best treatment options for you. Your plan depends on the type of kidney cancer you have and where it’s spread. Your doctor will also consider your overall health and treatment goals.

Immunotherapy

Combination immunotherapy is now a standard treatment for metastatic kidney cancer. It boosts your immune system to recognize and destroy cancer cells. Immune checkpoint inhibitors (ICIs) are commonly used in kidney cancer.

ICIs block proteins on cancer cells and immune cells that turn off the immune response, allowing your immune system to work better.

Examples of ICIs used in metastatic kidney cancer include:

• Avelumab (Bavencio)
• Ipilimumab (Yervoy)
• Nivolumab (Opdivo)
• Pembrolizumab (Keytruda)

TKIs and VEGF Inhibitors

Targeted therapies block proteins that cancer cells use to grow and multiply. One example is tyrosine kinase inhibitors (TKIs).

Some TKIs also stop kidney tumors from creating new blood vessels. They block vascular endothelial growth factor (VEGF). TKIs prevent tumors from getting oxygen and nutrients, shrinking them.

TKIs are taken as pills. For some people, they’re combined with other medications, like immunotherapies. Most TKIs are FDA-approved to treat RCC.

Examples of TKIs include:

• Axitinib (Inlyta)
• Cabozantinib (Cabometyx)
• Lenvatinib (Lenvima)
• Pazopanib (Votrient)
• Sorafenib (Nexavar)
• Sunitinib (Sutent)
• Tivozanib (Fotivda)

Your doctor will choose a TKI depending on other treatments you’ve tried before. For example, ICI-based combinations are now the preferred first treatment.

Sunitinib and pazopanib are alternative options in select cases. These are often the first medications given for metastatic RCC. If they stop working, you may receive cabozantinib or axitinib next.

Bevacizumab (Avastin) is a medication that blocks new blood vessel growth. It’s given as an infusion through a vein (IV) every two weeks.

Inhibitors of mTOR

Mammalian target of rapamycin (mTOR) inhibitors block the mTOR protein, which cancer cells use to grow and divide. Two mTOR inhibitors used in metastatic kidney cancer are everolimus (Afinitor) and temsirolimus (Torisel). Everolimus is a pill, and temsirolimus is given as an IV infusion.

Doctors can prescribe mTOR inhibitors alone or together with a TKI. For example, the combination of everolimus and lenvatinib is given as a second-line treatment. Temsirolimus can be given as a first-line treatment alone.

Belzutifan

Belzutifan (Welireg) is known as a hypoxia-inducible factor (HIF) inhibitor. It blocks a protein that helps cancer cells grow and form new blood vessels.

Belzutifan treats advanced RCC with a clear cell component after treatment with both an immune checkpoint inhibitor and a VEGF-targeted drug.

Surgery and Radiation Therapy

Surgery usually isn’t part of treating metastatic kidney cancer. However, the American Cancer Society notes it can be useful in some cases.

Most of the time, treatment includes systemic therapies first to shrink tumors. Smaller tumors are easier to treat with surgery or radiation therapy.

If you’re healthy enough, your doctor may recommend surgery if the primary tumor in your kidney can be removed and there’s limited cancer spread to other parts of the body, which can also be removed.

If only your kidney tumor is removable, doctors sometimes recommend a nephrectomy. This surgery removes the entire affected kidney.

You may then receive immunotherapy or other systemic therapy to help treat any remaining cancer cells. Radiation therapy can also help treat kidney cancer that’s spread to other organs.

Clinical Trials

Clinical trials are research studies that test new treatments or new ways to use current treatments. They may give you a chance to take part in a study testing those treatments.

Some oncology trials study brand-new drugs, while others look at combinations of approved medications. If you’re interested in joining a clinical trial for metastatic kidney cancer, talk to your cancer care team.

Metastatic Kidney Cancer Prognosis: What’s the Outlook?

According to the American Cancer Society, the five-year relative survival rate for metastatic kidney cancer is 19 percent. This compares people with metastatic kidney cancer with people in the general population.

The good news is that life expectancy with metastatic kidney cancer continues to improve. New treatments now help people live longer with advanced kidney cancer.

Join the Conversation

On MyKidneyCancerTeam, people share their experiences with kidney cancer, get advice, and find support from others who understand.

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