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INTRODUCTION — The kidneys are bean-shaped, approximately fist-sized organs that are located on each side of the mid-back, just below the rib cage (figure 1). The kidneys filter blood and get rid of excess water and waste in the urine.
The most common form of kidney cancer in adults is renal cell carcinoma (RCC). RCC usually does not cause obvious symptoms, especially in the early stages. As a result, the cancer may not be discovered until it is advanced.
Treatment of RCC may include surgery to remove part or all of a kidney. In some people, medicine is used to slow the growth of the cancer.
This article discusses the symptoms, diagnosis, and treatment options for RCC. More detailed information about RCC, written for health care providers, is also available by subscription. (See 'Professional level information' below.)
CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.
In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.
RENAL CELL CARCINOMA SYMPTOMS — Most people with renal cell carcinoma (RCC) do not have obvious symptoms. This means that RCC is sometimes not found until the cancer is advanced. When symptoms do occur, the most common ones include:
●Blood in the urine (hematuria)
●Pain in the sides of the mid-back (the flank)
●A palpable mass in the abdomen or side of the back
●Swelling around the left testicle
●Weight loss, night sweats, and/or unexplained fever
If you have any of these symptoms, talk to your doctor or nurse.
RENAL CELL CARCINOMA DIAGNOSIS — If you have symptoms of renal cell carcinoma (RCC), your doctor or nurse may order an imaging test, such as an ultrasound or computed tomography (CT) scan, to look at the kidneys. In many cases, however, the cancer is found when one of these tests is done for another reason and incidentally identifies an abnormal mass or growth in the kidney.
If you have an ultrasound that shows a growth on your kidney, a CT scan, generally before and after intravenous (IV) contrast injection, will be done. The CT scan may also tell if the growth appears cancerous and/or has spread outside the kidney (metastasized).
Unlike other cancers, a biopsy is not always needed to be sure that you have RCC. Instead, the diagnosis may be based on how the tumor looks on the CT scan. Later, the diagnosis is confirmed when the tumor or entire kidney is removed during surgery.
Staging — Once RCC is diagnosed, the next step is to determine its stage. Staging is a system used to describe the size, aggressiveness, and spread of a cancer. A cancer's stage helps to guide treatment and can help predict the long-term outlook.
An RCC's stage is based on:
●The size of the tumor
●Spread of the cancer to nearby lymph nodes, blood vessels, or tissue surrounding the kidney
●Signs of cancer in other organs (liver, lung, bone, etc)
RCC stages range from stage I, meaning the tumor is smaller than 7 cm (approximately 3 inches) and has not spread outside the kidney, to stage IV, meaning the tumor has spread beyond the outer layers of the kidney or to distant lymph node(s) or other organ(s).
In general, lower stage cancers are less aggressive or advanced and are less likely to come back after treatment compared with higher stage cancers. Stage I, II, and III RCCs are referred to as localized RCCs, while a stage IV RCC is referred to as an advanced or metastatic RCC.
LOCALIZED RENAL CELL CARCINOMA TREATMENT — The preferred treatment for most people with localized renal cell carcinoma (RCC) is surgery to remove part or all of the kidney and, if necessary, the nearby lymph nodes.
The decision to remove part or all of the kidney depends on your cancer's size, where it is located in your kidney, whether there is one or multiple tumors, and how well your kidneys work.
●If you have multiple tumors, or your tumor is large or located centrally within the kidney, complete removal of the kidney may be necessary, especially if your other kidney works normally. (See 'Radical nephrectomy' below.)
●In other situations or if your kidneys do not work well, removing part of the kidney may be a better option. (See 'Nephron-sparing treatments' below.)
Radical nephrectomy — "Radical nephrectomy" is the medical term for a surgery that removes the entire kidney and surrounding tissues. Most people can live normally with only one kidney.
Nephron-sparing treatments — Nephron-sparing treatments are treatments for RCC that do not remove the entire kidney. Normally, the kidneys filter waste out of the blood with tiny structures, known as nephrons. Nephron-sparing treatments allow some of the nephrons in the same kidney to continue working. This treatment is generally preferred if it is feasible, especially if your kidneys do not work well, a situation in which preserving as many nephrons as possible is a priority.
Nephron-sparing treatments include:
●Surgery to remove part of the kidney (called partial nephrectomy); this is the more common treatment.
●Treatment that destroys the cancer by burning it (called radiofrequency ablation) or freezing it (called cryoablation).
Treatment after surgery — For people with low-stage localized RCC, further treatment is not usually provided after surgery. Further treatment has not been proven to decrease the chance of the cancer returning or to extend life. However, for people with higher-stage localized RCC or tumors that are higher grade (ie, cancer cells and tissue that look more abnormal under a microscope and appear more likely to grow and spread), additional medical treatment may be used to decrease the chance of the cancer returning.
It is important to see your doctor on a regular basis after being treated for cancer to monitor for signs that the cancer has returned. (See 'Follow-up after local treatment' below.)
TREATMENT OF ADVANCED RENAL CELL CARCINOMA — For people with advanced or metastatic renal cell carcinoma (RCC), treatment with a medicine (called medical treatment) may be recommended instead of or along with surgery. Medical treatment may also be recommended if your cancer recurs after surgery.
Surgery to remove the kidney or areas outside the kidney where the cancer has spread (metastases) may be done before medical treatment. For someone with advanced RCC, surgery does not usually cure the cancer, but it can reduce symptoms or delay systemic medical treatment.
The most commonly used medical treatments for advanced RCC are:
●Immune therapy (also called immunotherapy) – This is the term for drugs that work with your immune system to stop or slow the growth of cancer cells. Currently, approved drugs include ipilimumab (an "anti-cytotoxic T-lymphocyte antigen-4 [CTLA-4] checkpoint inhibitor"), and nivolumab, pembrolizumab, and avelumab (drugs that block the anti-programmed cell death 1 [PD-1] pathway).
●Targeted therapy – This includes antiangiogenic therapies, a class of medicines that reduce the blood supply to the tumor, thus slowing or stopping the growth of the tumor, as well as other medicines that directly inhibit the growth of the cancer.
Advanced RCC is hard to cure. When possible, people with advanced RCC are encouraged to enroll in a clinical trial, as the optimal use of approved treatments and several promising not-yet-approved agents are still being investigated. (See 'Clinical trials' below.)
Immune therapy
Nivolumab — Nivolumab (brand name: Opdivo) is a type of drug called an anti-PD-1 checkpoint inhibitor that unleashes the body's immune system so it can reject the kidney cancer. Nivolumab is often given in combination with another drug, ipilimumab, particularly in patients who have not received prior treatment for advanced-stage disease. Treatment with nivolumab, either by itself or with a drug called cabozantinib (see 'Targeted therapies' below), may decrease the extent of your kidney cancer and help you live longer. Nivolumab can cause the body to develop an immune reaction against its own tissues. This can result in a wide range of side effects, which can be severe or life threatening, but they can be treated with drugs that suppress the immune system, such as prednisone.
Ipilimumab — Ipilimumab (brand name: Yervoy) is an "anti-CTLA-4 checkpoint inhibitor" that also uses the body's immune system to reject the kidney cancer. Ipilimumab is generally used in combination with nivolumab, although the combination has more side effects compared with nivolumab alone. The combination of nivolumab plus ipilimumab was found to be more effective at controlling disease than a blood vessel (vascular endothelial growth factor [VEGF] pathway) targeted therapy (see 'Targeted therapies' below) in patients with advanced-stage disease.
Pembrolizumab — Pembrolizumab (brand name: Keytruda) is another type of anti-PD-1 checkpoint inhibitor that uses the body's immune system to attack the cancer. It is often given in combination with either axitinib or lenvatinib, which are agents that target the blood vessels, particularly in patients who have not received prior treatment for advanced-stage disease (see 'Targeted therapies' below). These treatment combinations can help you live longer and may reduce symptoms related to your cancer. Pembrolizumab can cause side effects due to immune reactions against normal tissue.
Avelumab — Avelumab (brand name: Bavencio) is a type of drug called an anti-programmed cell death ligand 1 (PD-L1) checkpoint inhibitor that uses the body's immune system to attack the cancer. It is given in combination with axitinib, an agent that targets the blood vessels, in patients who have not received prior treatment for advanced-stage kidney cancer. The combination of avelumab plus axitinib is more effective at controlling disease than blood vessel (VEGF) targeted therapy in patients with advanced-stage kidney cancer. (See 'Targeted therapies' below.)
Targeted therapies — Targeted therapies are medicines designed to slow the growth of tumor cells. The medicines are called "targeted" because they work by interfering with a step in the cancer's growth process. Targeted therapies rarely cure the cancer, but they may allow you to live longer and to have fewer symptoms related to your cancer. These therapies are an option for people with advanced or metastatic RCC, either as an alternative to, after, or in combination with immunotherapy.
One set of these agents targets the VEGF pathway, which partly controls the growth of blood vessels. The blood vessels feeding RCC tumors are particularly dependent on VEGF, so treatment with anti-VEGF therapies can damage tumor blood vessels, and this may slow or stop the tumor from growing for long periods of time. Drugs in this category include:
●Pazopanib (brand name: Votrient)
●Sunitinib (brand name: Sutent)
●Cabozantinib (brand name: Cabometyx)
●Axitinib (brand name: Inlyta)
●Sorafenib (brand name: Nexavar)
●Bevacizumab (brand name: Avastin)
●Lenvatinib (brand name: Lenvima)
●Tivozanib (brand name: Fotivda)
A second target for treatment of RCC involves blocking a specific protein called the mechanistic (or mammalian) target of rapamycin (mTOR). These include:
●Temsirolimus (brand name: Torisel)
●Everolimus (brand name: Afinitor)
Some of these medicines are available as a pill that you take by mouth, while others are given into an IV. These medicines are typically given one at a time rather than in combination. The combination of lenvatinib plus everolimus may be offered to some people if initial treatment approaches fail. The most common side effects of mTOR inhibitors include rashes and fatigue, and for VEGF targeted therapy, they include fatigue and high blood pressure.
FOLLOW-UP AFTER LOCAL TREATMENT — Close follow-up after local treatment (radical nephrectomy or nephron-sparing treatment) is important for anyone with renal cell carcinoma (RCC). Follow-up visits allow your doctor to look for signs that the cancer has returned.
During a follow-up visit, you will have an exam, lab tests, and X-ray tests or CT scans. Depending on the stage of your cancer, these tests are recommended every 6 to 12 months for at least five years.
CLINICAL TRIALS — Progress in treating renal cell carcinoma (RCC) requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study new treatments or new treatment combinations. Ask for more information about clinical trials, or read about clinical trials at:
●www.cancer.gov/about-cancer/treatment/clinical-trials
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).
WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Kidney cancer (The Basics)
Patient education: What are clinical trials? (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
This topic currently has no corresponding Beyond the Basics content.
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Overview of the treatment of renal cell carcinoma
Clinical manifestations, evaluation, and staging of renal cell carcinoma
Epidemiology, pathology, and pathogenesis of renal cell carcinoma
Diagnostic approach, differential diagnosis, and management of a small renal mass
Systemic therapy of advanced clear cell renal carcinoma
Antiangiogenic and molecularly targeted therapy for advanced or metastatic clear cell renal carcinoma
The treatment of advanced non-clear cell renal carcinoma
Prognostic factors in patients with renal cell carcinoma
Radiofrequency ablation and cryoablation for renal cell carcinoma
Role of surgery in patients with metastatic renal cell carcinoma
Definitive surgical management of renal cell carcinoma
Surveillance for metastatic disease after definitive treatment for renal cell carcinoma
The following organizations also provide reliable health information.
●National Library of Medicine
(medlineplus.gov/ency/article/000516.htm)
●American Society of Clinical Oncology
(www.cancer.net/cancer-types/kidney-cancer)
●National Cancer Institute
●American Cancer Society
(www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html)
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