Clear-cell metastatic renal carcinoma means a kidney cancer that started in the kidney’s tiny tubules and now has spread to other parts of the body, such as the lungs, bones, liver, brain, or distant lymph nodes. “Clear-cell” describes how the cancer cells look under the microscope: their inside looks pale or clear because they are full of fat and sugar (glycogen). This type is the most common form of kidney cancer in adults and is usually more aggressive than many other kidney tumors. When it has spread beyond the kidney, doctors call it metastatic or stage 4 disease.
Clear-cell metastatic renal carcinoma is a type of kidney cancer that starts in the tiny filtering cells of the kidney (called proximal tubule cells) and has spread (metastasized) to other parts of the body such as lungs, bones, liver, or brain. “Clear-cell” describes how the cancer cells look pale or “clear” under the microscope because they contain fats and sugars. “Metastatic” means the cancer is no longer limited to the kidney and behaves as a whole-body disease that usually needs systemic (whole-body) therapy, not only local surgery. [1]
Clear-cell metastatic renal carcinoma is the most common subtype of renal cell carcinoma (RCC). Modern care is usually based on a mix of targeted drugs, immunotherapy (drugs that wake up the immune system), surgery when useful, and supportive care such as pain control, nutrition, and emotional support. Treatment is personalized based on risk group, spread pattern, kidney function, and the patient’s general health and wishes. [1][2]
In clear-cell metastatic renal carcinoma, cancer cells often grow from the cortex of the kidney (the outer layer where blood is filtered) and may break away, travel in blood or lymph, and form new tumors in other organs. The spread can happen to lymph nodes, lungs, liver, bones, adrenal glands, or brain. At this stage, cure is harder, and treatment usually focuses on making the cancer smaller, slowing its growth, and helping the person live longer with better quality of life.
Other names
Doctors and medical texts may use several different names for this cancer. All of the terms below are talking about the same basic condition or very close versions of it:
“Clear-cell renal cell carcinoma” (ccRCC) is the main name. It means a kidney (renal) cancer made of clear-looking cells.
“Metastatic clear-cell renal cell carcinoma” is the name when the clear-cell kidney cancer has already spread to other parts of the body.
“Stage 4 clear-cell RCC” or “stage IV clear-cell renal cell carcinoma” is the staging term for clear-cell kidney cancer that has spread outside the kidney to distant organs or to many lymph nodes.
“Clear-cell kidney cancer with metastasis” and “clear-cell metastatic renal carcinoma” are plain-language ways to say the same thing, often used in clinic letters or patient information pages.
Types
Doctors do not usually split metastatic clear-cell renal carcinoma into many brand-new diseases, but they describe “types” based on where and how it has spread, how it behaves, and how it looks under the microscope.
One way is to talk about synchronous metastases, where the cancer has already spread at the time the kidney tumor is first found. This often means the cancer was silent for a long time and is discovered late.
Another way is metachronous metastases, where doctors remove or treat the kidney tumor first and the spread to other organs is discovered months or years later. This pattern can happen even after a period when the person felt well.
Some cases are oligometastatic, which means there are only a few small metastatic tumors, for example one or two spots in the lungs or bone. In these cases, surgery or focused radiation on those few spots may sometimes be added to drug treatment.
Other cases are polymetastatic, meaning there are many metastatic tumors in several organs (for example, lungs, liver and bone at the same time). These people almost always need systemic therapy such as targeted drugs or immunotherapy, rather than local surgery alone.
Pathologists also describe low-grade and high-grade clear-cell RCC under the microscope. Low-grade cancer cells look a bit more like normal kidney cells and tend to grow more slowly. High-grade cells look very abnormal and usually behave more aggressively, with a higher chance to spread and grow fast.
Finally, doctors sometimes group cases by main site of spread, such as lung-dominant, bone-dominant, brain metastases, or liver-dominant disease, because each pattern can cause different symptoms and may need different imaging and supportive care.
Causes and risk factors
The exact cause of clear-cell metastatic renal carcinoma is not fully known. Most people develop it because several risk factors come together over time, including genes, lifestyle, and other health problems.
1. Smoking tobacco
Smoking cigarettes, cigars, or other tobacco is one of the strongest known risk factors for renal cell carcinoma. Harmful chemicals from smoke enter the bloodstream, reach the kidneys, and can damage the DNA of kidney cells. Over many years, this damage can lead to cancer changes in the cells that line the kidney tubules.
2. Overweight or obesity
Having excess body weight raises the risk of clear-cell kidney cancer. Extra fat tissue changes hormone levels and increases chronic inflammation, which can push kidney cells toward abnormal growth and cancer. Weight problems often combine with high blood pressure and diabetes, further increasing risk.
3. High blood pressure (hypertension)
Long-term high blood pressure strains the blood vessels and tiny filters in the kidney. Over time, this constant pressure may damage kidney tissue and change how cells repair themselves, increasing the chance of cancer. Some blood pressure medicines may also interact with other risks in complex ways, although the main risk is the high pressure itself.
4. Older age
Kidney cancer is more common in older adults, usually after age 60. Our cells collect small DNA errors as we age, and the body’s repair systems become less efficient. This normal aging process makes it more likely for kidney cells to turn cancerous and then later become metastatic if not found early.
5. Male sex
Renal cell carcinoma, especially clear-cell type, happens more often in men than in women. Hormone differences, higher smoking rates, and more exposure to some workplace chemicals in male-dominated jobs may all play a role in this difference.
6. Family history of kidney cancer
People with a close family member—such as a parent, brother, or sister—who had kidney cancer have a higher risk themselves. This may be due to shared genes that make cells less able to repair DNA damage, or shared lifestyle factors, or both.
7. Inherited von Hippel–Lindau (VHL) syndrome
VHL syndrome is a rare inherited condition that strongly increases the risk of clear-cell RCC. A faulty copy of the VHL gene causes abnormal cell growth and blood vessel growth, especially in the kidney. People with VHL often develop tumors at a younger age and may develop multiple kidney tumors that can later metastasize.
8. Other inherited RCC syndromes (for example, Birt–Hogg–Dubé)
Several rare inherited syndromes, such as Birt–Hogg–Dubé, hereditary leiomyomatosis and RCC, and others, also raise the risk of kidney cancers. In these conditions, specific gene changes make kidney cells more likely to turn into cancer and sometimes into clear-cell type.
9. Chronic kidney disease
Long-term kidney damage, from conditions like glomerulonephritis, diabetes, or high blood pressure, can lead to scarring and abnormal cell repair. In damaged kidneys, the remaining cells may grow faster to make up for lost function, which sometimes leads to cancer changes.
10. Long-term dialysis
People on dialysis for many years, especially more than 5–10 years, often develop acquired cystic kidney disease. These cysts can sometimes transform into renal cell carcinoma, including clear-cell type, and may eventually spread if not detected and treated early.
11. Acquired cystic kidney disease in dialysis patients
In acquired cystic kidney disease, multiple cysts appear in the kidneys after long-term kidney failure. The lining cells of these cysts can become unstable and turn into cancer, which may be clear-cell RCC and later metastasize.
12. Long-term use of some pain medicines
Long-term heavy use of certain pain medicines, including some older non-steroidal anti-inflammatory drugs (NSAIDs) and combination pain pills, has been linked to higher kidney cancer risk. These drugs may damage kidney tissue or change blood flow, leading to chronic irritation and DNA damage.
13. Exposure to workplace solvents (for example, trichloroethylene)
Working for many years with certain industrial chemicals, like trichloroethylene used in metal cleaning or degreasing, can increase the risk of kidney cancer. These chemicals may enter the body through breathing or skin and are filtered by the kidney, where they can damage cell DNA.
14. Exposure to heavy metals such as cadmium
Cadmium and some other metals used in batteries, paints, or welding can build up in the body and damage the kidneys. Long-term exposure has been linked with higher rates of kidney cancer in some workers.
15. Unhealthy diet low in fruits and vegetables
A diet high in processed foods and low in fruits and vegetables may raise kidney cancer risk. Antioxidants and vitamins in plant foods help protect cells from damage. Without these, kidney cells may face more oxidative stress, making cancer changes more likely.
16. Physical inactivity
Lack of regular exercise can lead to obesity, high blood pressure, and insulin resistance. These metabolic problems all increase the risk of renal cell carcinoma. In contrast, regular physical activity seems to lower risk by helping control weight, blood pressure, and inflammation.
17. Long-term uncontrolled diabetes
Poorly controlled diabetes damages small blood vessels in many organs, including the kidneys. This damage and chronic inflammation may contribute to increased cancer risk. Diabetes also often comes with obesity and high blood pressure, which add to the problem.
18. History of kidney stones and chronic kidney irritation
Kidney stones themselves do not directly cause cancer, but repeated stones and infections can irritate the kidney over many years. Chronic irritation and scarring may promote abnormal cell growth and, in some people, cancer change.
19. Chronic hepatitis C infection
Hepatitis C can affect not only the liver but also the kidneys, causing chronic inflammation and special types of kidney disease. Research has linked long-term hepatitis C with higher risk of kidney cancer, including clear-cell tumors.
20. Sickle cell trait or disease affecting the kidney
In some people with sickle cell disease or trait, abnormal red blood cells damage kidney tissue over time. This damage can lead to chronic kidney problems and is linked with a higher risk of certain kidney cancers.
Symptoms
Symptoms of clear-cell metastatic renal carcinoma can come from the kidney tumor itself or from the metastases in other organs. Many people have no symptoms in early stages, and problems often appear later when the disease is advanced.
1. Blood in the urine (hematuria)
A common sign is urine that looks pink, red, or cola-colored because of blood. Sometimes the blood is visible; other times, it is only found on a urine test. Blood appears because the tumor breaks small blood vessels inside the kidney or irritates the urinary tract.
2. Pain in the side or lower back (flank pain)
Dull or sharp pain in the side, back, or under the ribs can occur when the kidney tumor grows and presses on nearby tissues or nerves. The pain may be constant or may come and go, and it usually does not improve with simple movement or rest.
3. A lump or fullness in the belly or side
Some people can feel a lump or a sense of fullness in the abdomen or flank area. This lump is often the enlarged kidney or the tumor itself. Doctors may notice it during a physical exam, especially in thinner patients.
4. Unexplained weight loss
Many people with metastatic kidney cancer lose weight even when they are not trying. Cancer cells use a lot of energy and release substances that change how the body uses food, leading to loss of fat and muscle. This weight loss is often combined with loss of appetite.
5. Persistent tiredness or weakness
Long-lasting fatigue is very common. It can be caused by anemia (low red blood cells), by the cancer’s effect on metabolism, or by poor sleep due to pain or stress. People may feel exhausted after small tasks and need more rest than usual.
6. Fever that comes and goes without infection
Some people have fevers, night chills, or feeling hot and cold without any clear infection. These “paraneoplastic” symptoms occur because the tumor releases chemicals that reset the body’s temperature control.
7. Night sweats or hot flashes
Waking up with soaked clothes or sheets can be another sign of advanced cancer. Night sweats are related to fever and changes in the body’s immune and hormone activity caused by the tumor.
8. Loss of appetite or feeling full quickly
People may not feel hungry, or they may get full after just a few bites. This can come from tumor pressure on the stomach or intestines, or from body-wide chemical signals from the cancer that reduce appetite.
9. Shortness of breath with activity or at rest
If the cancer has spread to the lungs, people may notice they get out of breath more easily, have trouble climbing stairs, or feel breathless even at rest. Fluid around the lungs or anemia can also make breathing harder.
10. Persistent cough or chest discomfort
Lung metastases can cause a long-lasting cough, chest tightness, or sometimes coughing up small amounts of blood. These symptoms are usually slow to appear and may be mistaken for infection or smoking-related problems at first.
11. Bone pain or easy bone fractures
When cancer spreads to bones, it can cause deep, aching pain, especially at night or with movement. Bones weakened by metastases may break with minor falls or normal daily activity, leading to sudden severe pain.
12. Headaches, confusion, or seizures
Brain metastases can lead to new headaches, changes in memory or behavior, blurred vision, or seizures. These symptoms happen because tumors in the brain increase pressure or irritate brain tissue.
13. Swelling of the legs or ankles
Metastatic kidney cancer can block blood vessels or lymph channels, causing fluid to build up in the legs. Low blood protein from poor nutrition or liver involvement can also cause ankle or leg swelling.
14. Newly high or hard-to-control blood pressure
Some kidney tumors produce hormones or other substances that raise blood pressure. People may notice headaches, dizziness, or that their usual blood pressure pills are not working as well.
15. Nausea, vomiting, or general feeling of being unwell
Metastatic disease can make people feel sick to their stomach, with nausea and sometimes vomiting. High blood calcium, pain medicines, or involvement of the liver or digestive system can all contribute to this general unwell feeling.
Diagnostic tests
Doctors use a group of tests to diagnose clear-cell metastatic renal carcinoma, to see how far it has spread, and to plan treatment. These tests are grouped into physical exam, manual tests, lab and pathological tests, electrodiagnostic tests, and imaging tests.
1. General physical examination
The doctor looks at the whole body, checking weight, temperature, heart rate, breathing, and general appearance. They look for signs like weight loss, pale skin, fever, or swelling. A good physical exam helps guide which further tests are needed and may reveal clues such as enlarged lymph nodes or leg swelling.
2. Abdominal and flank examination
The doctor gently presses (palpates) the abdomen and sides to feel for any mass, tenderness, or fullness near the kidneys. In some people, a large kidney tumor can be felt as a firm lump. This simple hands-on exam can suggest a kidney problem even before imaging is done.
3. Lymph node examination
The doctor feels for enlarged lymph nodes in the neck, armpits, and groin. Swollen, firm nodes can be a sign that the cancer has spread through the lymphatic system. This helps in staging and in deciding whether to image specific areas more closely.
4. Manual blood pressure measurement
Using a cuff and stethoscope, the doctor measures blood pressure in both arms. Many people with renal cell carcinoma have high blood pressure, either as a cause or as a result of the tumor. Tracking blood pressure helps in diagnosis, in assessing paraneoplastic syndromes, and in planning safe treatment.
5. Performance status assessment, such as ECOG scale
The clinician talks with the patient and may ask simple tasks (like walking into the room) to rate how active they are. The ECOG or similar scale places people from fully active to mostly bedridden. This “manual” functional test helps decide which treatments (strong or gentle) are safe and realistic.
6. Focused bone and joint examination for tenderness
The doctor presses over the spine, ribs, and major bones and asks about pain. Increased tenderness may suggest bone metastases. This bedside test guides the need for imaging such as bone scan or MRI in painful areas.
7. Urinalysis (urine test)
A simple urine test checks for blood, protein, and other substances. Microscopic blood in urine is common in kidney cancer, even when the urine looks normal. Urinalysis also helps rule out infection or stones as other causes of symptoms.
8. Blood chemistry tests including creatinine and eGFR
Blood chemistry measures kidney function (creatinine, eGFR), electrolytes, and other markers. These results show how well the kidneys are working and whether they can safely handle surgery or certain drugs. Abnormal values may also suggest widespread disease.
9. Complete blood count (CBC)
A CBC measures red cells, white cells, and platelets. Many people with metastatic kidney cancer have anemia (low red cells) or abnormal platelets. Some may have high red cell counts because the tumor makes extra erythropoietin, a hormone that stimulates red cell production.
10. Liver function tests
Blood tests for liver enzymes and bilirubin check whether the liver is affected, either by metastases or by other conditions. Abnormal liver tests can change treatment choices and may trigger liver imaging to look for metastasis.
11. Serum calcium and electrolytes
High blood calcium (hypercalcemia) is a common paraneoplastic problem in renal cell carcinoma and can cause confusion, nausea, and constipation. Measuring calcium and other electrolytes helps detect this early so doctors can treat it quickly and modify cancer therapy if needed.
12. Lactate dehydrogenase (LDH) level
LDH is a blood enzyme that can rise when there is a large amount of active tumor. High LDH is used in some risk scores for metastatic RCC and may signal more aggressive disease. It helps doctors discuss prognosis and choose appropriate drug combinations.
13. Percutaneous needle biopsy of the kidney or metastasis
A radiologist inserts a thin needle into the kidney mass or a metastatic lesion, usually guided by ultrasound or CT. Small cores of tissue are removed and sent to pathology. Biopsy provides the final proof that the tumor is clear-cell RCC and not another type of cancer.
14. Histopathology (microscopic study) of the tumor tissue
Under the microscope, the pathologist looks at cell shape, pattern, and grade. Clear-cell RCC shows cells with clear or pale cytoplasm and a certain growth pattern. The histologic grade (low or high) helps predict how fast the tumor may grow and spread.
15. Immunohistochemistry panel on tumor cells
Special stains are added to the tumor tissue to highlight certain proteins. Clear-cell RCC often stains positive for markers like PAX8 and CA9, and usually negative for CK7, which helps distinguish it from other kidney tumors. Correct immunohistochemical profile is important to confirm the diagnosis and choose the right treatment.
16. Electrocardiogram (ECG)
An ECG records the electrical activity of the heart. People with metastatic cancer may have heart strain from anemia, high blood pressure, or drug side effects. Checking the ECG before and during treatment helps make sure the heart can safely tolerate therapies such as targeted drugs or immunotherapy.
17. Electroencephalogram (EEG) in patients with brain symptoms
If a person has seizures or unexplained confusion and is known to have metastatic kidney cancer, doctors may do an EEG to measure brain electrical activity. Abnormal patterns can support the possibility of brain involvement and guide urgent imaging and seizure treatment.
18. CT scan of abdomen and pelvis with contrast
Contrast-enhanced CT is the main imaging test for kidney cancer. It shows the size and location of the kidney tumor, involvement of blood vessels, lymph nodes, and nearby organs. CT also helps guide biopsy and is essential for staging and monitoring response to treatment.
19. Chest CT or chest X-ray to look for lung metastases
Because clear-cell RCC often spreads to the lungs, imaging of the chest is routine. A chest CT scan is more sensitive than a plain X-ray and can find even small metastatic nodules. Finding lung metastases changes the stage to metastatic disease and guides systemic therapy choices.
20. Magnetic resonance imaging (MRI) or bone scan for brain or bone spread
MRI gives detailed pictures of the brain and spine and is used when there are neurological symptoms. Bone scans or MRI of bones are used when there is bone pain or high suspicion of bone metastases. These imaging tests help map all metastatic sites so doctors can plan radiotherapy, surgery, or other local treatments along with systemic drugs.
Non-pharmacological treatments
Specialist education and shared decision-making
A clear, calm discussion with an oncologist and kidney specialist helps you understand the stage, treatment options, benefits, and side effects. Simple drawings, written plans, and family meetings can reduce fear and confusion. This approach lets you share your values and life goals so the team can choose treatments that match what matters most to you. [1]Structured physical activity and exercise
Gentle but regular activity such as walking, light cycling, or supervised strength exercises can improve energy, mood, and physical function during and after treatment. Studies in cancer survivors show exercise can lower fatigue and may improve survival when done safely with medical advice, often working like a “natural medicine” for the whole body. [3][4]Individualized nutrition counselling
Meeting a dietitian who understands both cancer and kidney health helps you choose foods that support weight, protein needs, and fluid balance. The plan usually focuses on vegetables, fruits, whole grains, healthy fats, and appropriate protein while adjusting salt, potassium, or phosphorus if kidney function is reduced. [3][5]Smoking cessation support
Stopping smoking can lower the risk of other cancers, heart disease, lung disease, and may improve treatment tolerance. Tools include counselling, nicotine replacement, and medicines. Even if cancer has already spread, quitting smoking can still improve breathing, wound healing, and overall survival. [1][6]Alcohol moderation or avoidance
Limiting alcohol helps protect the liver, heart, and brain, and can reduce interaction problems with anti-cancer drugs. For many people with metastatic cancer, “low or no alcohol” is safest, especially if they are losing weight or taking medicines that stress the liver. [3][7]Psychological counselling and coping skills
Talking with a psychologist, counsellor, or oncology social worker can help with anxiety, sadness, and fear about the future. Simple tools like breathing exercises, problem-solving therapy, and mindfulness can make it easier to sleep, talk to family, and stay engaged with treatment. [3]Support groups and peer programmes
Meeting other people living with kidney cancer, either in person or online, gives emotional support and practical tips about treatment and daily life. Hearing real stories can reduce loneliness and help patients ask better questions during clinic visits. [3]Palliative care (supportive care) early in the illness
Palliative care is not only for the last days of life. A palliative care team can help from early on with pain control, nausea, breathlessness, fatigue, and emotional stress. Evidence shows early palliative care can improve quality of life and sometimes even survival in advanced cancers. [1][3]Physical therapy and occupational therapy
Physiotherapists design safe exercise plans to keep muscles strong, improve balance, and reduce fall risk. Occupational therapists help with daily tasks such as dressing, bathing, or working by suggesting tools, home changes, or energy-saving techniques. [3]Pain management using non-drug methods
Alongside pain medicines, non-drug methods like heat packs, gentle massage, relaxation training, music therapy, and guided imagery can reduce the feeling of pain and help people rely on lower doses of strong painkillers. These methods are often low-risk and can be done at home. [3]Sleep hygiene and fatigue management
Simple habits such as keeping a regular sleep schedule, limiting caffeine late in the day, and having a quiet, dark bedroom can improve sleep. Planning daytime activities with rest breaks and prioritizing important tasks can help manage cancer-related tiredness. [3]Infection-prevention habits
Good handwashing, staying away from people with active infections, keeping vaccinations up to date when appropriate (such as flu and COVID-19), and quick reporting of fevers are all simple, non-drug ways to lower infection risk during treatment. [1][2]Kidney-protective lifestyle measures
Avoiding dehydration, limiting unnecessary non-steroidal painkillers, and controlling blood pressure and blood sugar can protect any remaining kidney function. This is important because many RCC drugs and scans can stress the kidneys. [5][6]Financial and social work support
Social workers can help with applications for insurance, travel help, disability benefits, and work adjustments. Reducing financial stress can make it easier for patients to stick to their treatment schedule and attend all visits. [3]Advance care planning and documented wishes
Discussing and recording wishes about future care (such as resuscitation preferences, where you would like to receive care, and who can speak for you) helps the team act according to your values if you cannot speak for yourself later. This planning can reduce stress for families. [3]Spiritual or meaning-focused care (if desired)
Some people find comfort in talking with chaplains, religious leaders, or spiritual counsellors about questions of meaning, hope, and fear. This kind of support can improve emotional wellbeing and help people feel more at peace with their decisions. [3]Telehealth and remote monitoring
Telephone, video visits, and symptom-tracking apps allow quick contact with the care team for questions, side-effects, or new symptoms. Early reporting helps doctors adjust medicines and avoid emergencies, especially for people who live far away from cancer centres. [1]Symptom and side-effect diaries
Keeping a simple notebook or using an app to record daily pain, appetite, bowel changes, energy, and mood helps both patients and doctors see patterns. This makes it easier to adjust treatment or supportive care in a targeted way. [1]Caregiver support and training
Teaching family caregivers how to help safely with medicines, mobility, nutrition, and emotional support can lower caregiver stress and improve patient comfort. Good caregiver support is a key part of maintaining quality of life at home. [3]Rehabilitation after surgery or major treatment changes
After nephrectomy or other big procedures, rehabilitation programmes focus on gentle training, breathing exercises, and activity planning to recover strength and independence. This can shorten recovery time and help patients restart systemic therapy safely. [1][3]
Drug treatments
Important: Drug information below is based on FDA-approved labels and guidelines and is written for general education. It is not a dosing guide for self-treatment. All cancer medicines must be prescribed and monitored by an oncology team. [1][2]
Nivolumab (OPDIVO)
Nivolumab is an immune checkpoint inhibitor that targets PD-1 on T-cells, helping the immune system recognize and attack cancer cells. It is approved for advanced RCC, either alone after previous therapies or in combination with ipilimumab or cabozantinib in the first-line setting. Usual dosing is an intravenous infusion every 2–4 weeks, adjusted by body weight or as a flat dose. Common side effects include fatigue, rash, diarrhea, and immune-related inflammation of organs such as lungs or colon. [1][2][8]Ipilimumab (YERVOY) – in combination with nivolumab
Ipilimumab blocks CTLA-4, another “brake” on T-cells. When combined with nivolumab, it can produce deep and sometimes long-lasting responses in intermediate or poor-risk clear-cell metastatic RCC. It is usually given at a lower dose than nivolumab for four cycles, followed by nivolumab alone. Side effects are mainly immune-related, including colitis, hepatitis, and hormone gland problems, so close monitoring is essential. [1][2][9]Nivolumab + cabozantinib (CABOMETYX)
This combination pairs nivolumab with cabozantinib, a tyrosine kinase inhibitor (TKI) that blocks VEGF and other growth signals that tumors use to grow blood vessels. It is approved as a first-line option for advanced RCC and can improve response rates and survival compared with older therapies. Cabozantinib is taken as daily tablets; common side effects include diarrhea, hand-foot syndrome, high blood pressure, and fatigue. [1][2][10]Pembrolizumab (KEYTRUDA) + axitinib (INLYTA)
This widely used first-line combination uses pembrolizumab (another PD-1 inhibitor) with axitinib (a VEGF-targeting TKI). The pairing aims to both wake up the immune system and cut off blood supply to the tumor. Pembrolizumab is given by IV every few weeks, and axitinib is taken orally twice daily. Side effects include immune-related events, diarrhea, high blood pressure, and hand-foot skin reactions. [1][2][11]Pembrolizumab + lenvatinib (LENVIMA)
In this combination, pembrolizumab is combined with lenvatinib, another VEGF-targeted TKI with additional targets. It is approved as a first-line therapy for advanced RCC. Lenvatinib is usually taken once daily along with pembrolizumab infusions. Side effects can include high blood pressure, diarrhea, appetite loss, and fatigue, and careful dose adjustments are often needed. [1][2][12]Lenvatinib + everolimus (AFINITOR)
This targeted combination is used after prior anti-angiogenic therapy. Lenvatinib blocks angiogenesis (new blood vessel growth), while everolimus blocks mTOR, a pathway involved in cell growth. Both are oral medicines taken daily. Common side effects include mouth sores, diarrhea, fatigue, and metabolic changes such as high cholesterol or high blood sugar, so regular blood tests are needed. [1][2][13]Cabozantinib (CABOMETYX) as single-agent
Cabozantinib can be used alone in advanced RCC, including after prior treatments. By blocking VEGF and MET/AXL pathways, it helps slow tumor growth and reduce blood supply to the cancer. It is taken as tablets once daily. Side effects may include diarrhea, mouth sores, fatigue, hand-foot syndrome, and increased risk of blood clots or bleeding, so monitoring is important. [2][10]Axitinib (INLYTA) as single-agent
Axitinib is an oral TKI that mainly targets VEGF receptors and can be used alone, especially after prior systemic therapies. Its dose can sometimes be increased if tolerated. Common side effects include high blood pressure, diarrhea, nausea, fatigue, and voice changes. The medicine is usually taken twice daily with or without food. [2][11]Sunitinib (SUTENT)
Sunitinib is an older but still important oral TKI that targets several receptors, including VEGF and PDGF. It was one of the first standard first-line treatments for RCC and is still used, especially where newer combinations are not available. Usual dosing is 50 mg once daily in 4-weeks-on/2-weeks-off cycles, with side effects such as fatigue, mouth sores, hand-foot syndrome, and high blood pressure. [2][14]Pazopanib (VOTRIENT)
Pazopanib is another VEGF-targeting TKI taken orally, often once daily. It is approved for advanced RCC and may be chosen when patients prefer continuous dosing rather than on/off cycles. Side effects include liver test abnormalities, high blood pressure, diarrhea, hair color changes, and fatigue, so liver function needs close monitoring. [2][15]Sorafenib (NEXAVAR)
Sorafenib is an older TKI that blocks several growth and blood-vessel pathways. It is approved for advanced RCC and is taken as tablets twice daily. It is now less commonly used as first-line therapy in clear-cell metastatic disease but still has a role in some settings. Typical side effects are rash, hand-foot skin reaction, diarrhea, and high blood pressure. [2][16]Everolimus (AFINITOR) as single-agent
Everolimus is an oral mTOR inhibitor that slows cell growth and is helpful after prior VEGF-targeted treatments such as sunitinib or sorafenib. It is taken once daily and can cause mouth ulcers, rash, high cholesterol, high blood sugar, and low blood counts. It is sometimes used alone or in combination as described above. [2][13]Tivozanib (FOTIVDA)
Tivozanib is an oral TKI specifically designed to inhibit VEGF receptors. It is approved in relapsed or refractory advanced RCC after at least two prior systemic therapies. It is usually dosed once daily for 21 days followed by 7 days off in a 28-day cycle. Side effects include high blood pressure, fatigue, and diarrhea. [2][17]Avelumab (BAVENCIO) + axitinib (INLYTA)
Avelumab is a PD-L1 inhibitor that can be combined with axitinib as an immunotherapy-TKI pairing in advanced RCC. Avelumab is infused every 2 weeks while axitinib is taken orally. This combination aims to boost immune attack while blocking blood-vessel growth. Side effects include immune-related inflammation, infusion reactions, and TKI-related toxicity. [1][2][18]Belzutifan (WELIREG)
Belzutifan is a newer oral hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor that targets a pathway especially important in clear-cell RCC. It is approved for advanced RCC with a clear-cell component after prior PD-1/PD-L1 inhibitor and VEGF-TKI therapy. It is taken as 120 mg once daily and can cause anemia, low oxygen levels, and fatigue, so regular blood checks are essential. [2][19]Interleukin-2 (aldesleukin, PROLEUKIN)
High-dose interleukin-2 is an older immune therapy that can, in a small group of carefully selected patients, produce long-lasting complete responses. It works by strongly stimulating immune cells but has serious side effects such as low blood pressure, fluid leakage, and organ stress, so it is only given in specialized centres with intensive monitoring. Its use is now more limited due to modern checkpoint inhibitors. [2][20]
(Other TKIs and immunotherapies, as well as clinical-trial medicines, may be used based on individual factors and evolving guidelines.)
Dietary molecular supplements
Important: Supplements can interact with cancer medicines or harm kidneys. They must always be discussed with the oncology and nephrology team before use. The points below summarize research trends, not personal medical advice. [3][5]
Vitamin D
Vitamin D supports bone health, muscle function, and immune regulation. Many people with cancer have low levels. A typical medical approach is to check blood levels and give a doctor-chosen dose if low. Too much vitamin D can damage kidneys and raise calcium levels, so it must be supervised and adjusted based on lab tests. [3][5]Omega-3 fatty acids (fish oil)
Omega-3 fats from fish oil or algae may help reduce inflammation and support appetite and weight in some cancer patients. Low to moderate doses, if allowed by kidney function and blood-thinning status, are usually used. High doses can increase bleeding risk, especially with TKIs and anticoagulants, so oncologists should review all medicines first. [3]High-protein oral nutrition supplements
For people losing weight or muscle, high-protein drinks or powders can help meet daily protein and calorie needs when eating is difficult. The dietitian adjusts amount and type according to kidney function, because severe chronic kidney disease may require lower protein. The goal is to prevent muscle loss and support healing, not to “cure” cancer. [3][5]Probiotics (with medical approval)
Certain probiotic products may help reduce some treatment-related gut problems and support a healthy microbiome. However, in people with very low immunity or central lines, some strains can rarely cause infection, so doctors must judge safety. Food sources like yogurt or fermented foods are often preferred if tolerated. [3]Soluble fibre supplements (e.g., psyllium)
Gentle soluble fibre can help manage constipation or diarrhea, especially when opioids or TKIs upset bowel habits. Adequate fluids are needed for safe use. People with strictures, bowel obstruction, or very low fluid allowance should avoid or use only under close supervision. [3][5]Curcumin (turmeric extract) – cautious use
Curcumin has anti-inflammatory and antioxidant actions in lab studies, and early research explores its role with cancer therapies. But it can interact with drug-metabolizing enzymes and blood-thinning pathways. In metastatic RCC, any concentrated curcumin product should be reviewed with the oncology team before use. [3]Green tea extract – cautious use
Green tea contains catechins with antioxidant effects. Some small studies suggest possible benefits in cancer prevention, but high-dose extracts have been linked to liver injury in some people. For patients on multiple RCC drugs, it is safer to use modest amounts of brewed tea, if allowed, rather than strong capsules. [3]Oral bicarbonate or citrate (only if prescribed)
Sometimes, kidney specialists prescribe bicarbonate or citrate solutions or tablets to correct acid-base problems linked to reduced kidney function. These are not general supplements and must only be used when clearly ordered, because wrong dosing can upset salts and fluid balance. [5]Multivitamin without high doses of fat-soluble vitamins
A simple, low-dose multivitamin can help cover general micronutrient gaps when appetite is poor. Products that avoid very high doses of vitamins A, E, and K are usually preferred in cancer and kidney patients to reduce toxicity and drug interaction risk. [3]Medical-grade nutrition formulas for tube feeding
For people who cannot eat enough by mouth, specialized liquid formulas may be used via feeding tube. Dietitians choose formulas that match kidney function, calorie needs, and treatment plans. This is a structured medical intervention, not an over-the-counter supplement. [5]
Immunity-supporting and “regenerative / stem-cell–related drugs
Immune checkpoint inhibitors as immune “re-activators”
Medicines like nivolumab and pembrolizumab are sometimes called immune checkpoint inhibitors. They remove brakes on T-cells so the immune system can better see and attack cancer cells. This is a kind of “immune boosting,” but it is very specific and powerful, with possible serious immune side effects, so it must only be used under oncology supervision. [1][2]CTLA-4 blockade (ipilimumab)
Ipilimumab further amplifies immune activation when combined with nivolumab. This broader immune stimulation can lead to durable responses but also raises the risk of severe immune-related side effects affecting the gut, liver, skin, or hormones. It is not a general “vitamin-like booster”; it is a strong cancer drug used with intensive monitoring. [1][2][9]High-dose interleukin-2 (aldesleukin)
High-dose IL-2 can expand and activate certain immune cells so they attack cancer more aggressively. A small fraction of metastatic RCC patients get long-lasting complete responses, but the treatment is risky and requires an intensive-care-capable hospital. It is only offered to very fit patients and is not a routine option for most people. [2][20]Granulocyte colony-stimulating factors (G-CSF)
Sometimes, drugs that stimulate white blood cell production are used if chemotherapy or targeted drugs cause very low neutrophil counts. These medicines help the body recover defense against infection. They support immunity but do not directly shrink tumors in RCC. Oncologists decide if and when they are needed. [2]Experimental cell-based or vaccine-type therapies
Researchers are studying tumor vaccines and cell-based treatments where a patient’s immune cells are collected, changed in the lab, and returned to the body to better attack RCC. At present, these are mostly in clinical trials and are not standard care. They may be offered in research centres under strict protocols. [1]Stem-cell transplantation (not standard for metastatic clear-cell RCC)
Stem-cell or bone marrow transplants are standard for some blood cancers but not routine for metastatic clear-cell RCC. Very rarely, transplant-related strategies might be explored in trials or special cases, but for most patients, the mainstay is targeted therapy and immunotherapy, not stem-cell drugs. [1]
Surgeries and procedures
Radical nephrectomy (removal of the whole kidney)
Radical nephrectomy removes the cancer-bearing kidney and sometimes nearby tissue or lymph nodes. In metastatic disease, it may be done as “cytoreductive nephrectomy” to lower overall tumor burden in selected patients who are fit and whose metastases are limited. It can reduce bleeding, pain, or other local symptoms. [1]Partial nephrectomy (kidney-sparing surgery)
Partial nephrectomy removes only the tumor and a rim of normal tissue, preserving more kidney function. It is mainly used for smaller tumours or in people with a single kidney. For metastatic disease, it may be considered if local control is needed and anatomy allows. [1]Metastasectomy (removal of metastases)
In some patients with a few metastases, surgery to remove lesions from lung, liver, or bone can help control disease, reduce pain, or in rare cases lead to long-term remission when combined with systemic therapy. Decisions depend on location, number of lesions, and overall health. [1]Ablative procedures (radiofrequency or cryoablation)
When open surgery is not possible, interventional radiologists can use needles guided by imaging to freeze (cryoablation) or heat (radiofrequency ablation) small tumors in kidney or metastases. These minimally invasive procedures can control pain or local growth with shorter recovery time. [1]Palliative surgery for complications
Sometimes, surgery is done not to cure, but to solve problems such as severe bleeding, blockage of urine outflow, or spinal cord compression from bone metastases. These operations aim to improve comfort, mobility, or safety and are often combined with radiotherapy and systemic drugs. [1]
Preventions and risk-reduction
Avoid tobacco use and seek help to quit if already smoking. [1][6]
Maintain a healthy body weight with balanced food and regular activity. [3]
Control high blood pressure and diabetes with lifestyle and medicine. [5]
Limit long-term unnecessary NSAID use where possible, under medical advice. [5]
Stay physically active most days of the week, at a level that feels safe. [3][4]
Choose mainly plant-focused meals with vegetables, fruits, whole grains, and beans. [3]
Limit processed meats, sugary drinks, and very salty fast foods. [3][7]
Protect kidneys by avoiding dehydration and checking kidney function during illnesses. [5]
For people with inherited RCC risk, follow specialist advice on imaging and screening. [1]
Keep up with recommended vaccinations and routine health checks. [1][3]
When to see doctors (or seek urgent help)
You should contact a doctor or oncology team promptly if you have:
New or worsening blood in urine, persistent flank pain, or a new lump in the abdomen.
New or severe shortness of breath, chest pain, or strong cough, especially with blood.
Sudden strong bone pain, difficulty walking, or signs of spinal cord compression such as weakness or loss of control of bladder or bowel.
Fever, chills, or signs of infection while on systemic therapy.
Sudden severe headaches, confusion, or vision changes that could suggest brain involvement or treatment side effects.
Fast weight loss, poor appetite, or vomiting that does not settle.
Any severe or unusual symptom after starting a new drug, especially diarrhea, jaundice, rash, or shortness of breath, which may be immune-related side effects.
In emergencies (for example, trouble breathing, chest pain, or signs of stroke), urgent hospital care is needed. [1][2][3]
What to eat and what to avoid
Eat plenty of colourful vegetables and fruits
Aim to include vegetables and fruits at most meals to provide vitamins, minerals, and fibre. Soft, cooked options may be easier if appetite is low. [3][5]Choose whole grains when possible
Foods like brown rice, whole-wheat bread, and oats provide steady energy and fibre. Kidney function and potassium levels may affect choices, so a dietitian can personalize the plan. [3][5]Include moderate, high-quality protein
Lean poultry, eggs, fish, tofu, or lentils (if allowed) can support muscle repair during treatment. Amount and type depend on kidney function; your team will advise about safe protein targets. [3][5]Prefer healthy fats
Use small amounts of unsaturated fats such as olive oil, nuts, seeds, and avocado if allowed. These help maintain weight when appetite is low and support heart health. [3]Stay well hydrated as advised
Water and suitable fluids are important to support kidneys and prevent dehydration, but some patients with reduced kidney or heart function may need limits, so always follow individual advice. [5]Limit very salty, heavily processed foods
Processed meats, instant noodles, and salty snacks can worsen blood pressure and fluid retention. Cutting down salt helps protect remaining kidney function and the heart. [3][5]Avoid raw or undercooked animal products if immunity is low
Undercooked meat, eggs, and unpasteurized dairy can carry germs. Well-cooked foods and safe food handling are important when immune function is weakened by treatment. [3]Be cautious with herbal products and strong supplements
Many “natural” products can interact with RCC medicines or harm the liver and kidney. Never start new herbs or high-dose supplements without checking with your oncology and kidney team. [2][3]Limit or avoid alcohol
Alcohol can worsen liver stress and interact with many cancer drugs. Most guidelines suggest little or no alcohol for people with metastatic cancer, especially when taking systemic therapy. [3][7]Adapt eating style to symptoms
For nausea, small, frequent snacks and cold foods may be easier. For mouth sores, soft, non-acidic foods are gentler. A dietitian can suggest practical changes to keep eating as comfortable as possible. [3]
Frequently asked questions
Is clear-cell metastatic renal carcinoma curable?
When RCC has already spread to distant organs, cure is uncommon, but some people achieve long-term control or even complete responses, especially with modern immunotherapy combinations. The main goals are to extend life, reduce symptoms, and keep quality of life as high as possible. [1][2]Why are there so many different drug options?
Clear-cell RCC uses several growth and immune pathways. Different drugs target VEGF, mTOR, or immune checkpoints. Using combinations or changing drugs over time helps doctors manage resistance and find a regimen that fits each person’s health, side-effects, and response. [1][2]How do doctors choose my first treatment?
They look at risk category, tumor burden, symptoms, kidney function, age, other illnesses, and your own preferences. For many people, a combination of immunotherapy plus a TKI is chosen because it offers strong responses and survival benefits in guidelines. [1][2]If one treatment stops working, are there others?
Yes. Many patients move through several lines of therapy over time, such as starting with immunotherapy + TKI, then switching to another TKI, mTOR inhibitor, or newer drugs like belzutifan, depending on prior treatments and tolerance. [1][2][19]Will treatment damage my remaining kidney function?
Some RCC medicines, imaging contrast, and other drugs can affect kidney function. Doctors monitor blood tests regularly and adjust doses, change medicines, or involve nephrologists to protect the kidneys as much as possible. [2][5]Do I always need surgery if the cancer has spread?
Not always. Cytoreductive nephrectomy is helpful only in selected patients. In others, starting with systemic therapy without surgery is better. The decision is based on performance status, sites of spread, and how quickly the disease is growing. [1]Can lifestyle really make a difference after diagnosis?
Yes. While lifestyle cannot replace treatment, regular activity, balanced nutrition, stopping smoking, and good sleep can help you tolerate therapy better, maintain strength, and may modestly improve survival in many cancers. [3][4][21]Are there special diets that “kill” kidney cancer?
No single diet or food can cure cancer. Extreme diets can actually cause weight loss, weakness, and missing nutrients, making treatment harder. A balanced, plant-forward eating pattern, adjusted for kidney health, is the safest and most evidence-based approach. [3][7]Should I take lots of supplements to boost my immunity?
High-dose or multiple supplements are not proven to cure or control RCC and can sometimes be harmful or interact with medicines. Any supplement should be carefully discussed with the oncology and kidney teams before use. [2][3][5]What side effects should I report immediately?
You should urgently report severe diarrhea, fever, chest pain, shortness of breath, yellow eyes, extreme fatigue, confusion, or rapid weight changes. These may be signs of serious drug side effects or complications that need quick treatment. [2][8][9]Is it safe to have children after treatment?
Many RCC medicines can harm a developing baby, and some may affect fertility. People who may want children later should ask about sperm banking or egg/embryo freezing before treatment. Effective contraception is essential during and often after therapy. [2]Can I keep working or studying during treatment?
Some people continue part-time or flexible work or study during therapy, while others need more rest. Fatigue, clinic visits, and side effects vary. A social worker or employer/teacher can help plan adjustments. Listening to your body and pacing yourself is important. [3]Are clinical trials worth considering?
Clinical trials can offer access to new combinations or drugs and help improve future care. Doctors review eligibility, risks, and benefits with you. Participation is always voluntary, and you can leave a trial at any time. [1][2]How often will I need scans and blood tests?
During active systemic therapy, scans are usually done every few months to check response, and blood tests may be done every treatment cycle to monitor counts, kidney and liver function. The exact schedule depends on your regimen and how stable things are. [1][2]Where can I find reliable information and support?
Reliable sources include major kidney cancer guidelines, national cancer societies, kidney foundations, and large academic cancer centres. Patient-focused guideline summaries and survivorship resources from trusted organizations are easier to read and regularly updated. [1][3][25]
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 28, 2025.
