Renal cell carcinoma is the most common type of kidney cancer in adults, and treatment approaches have evolved significantly in recent years. Whether the cancer is caught early or has spread, a range of options exist to help control the disease, manage symptoms, and improve quality of life.

Understanding Treatment Goals for Kidney Cancer

When someone receives a diagnosis of renal cell carcinoma, often called RCC or kidney cancer, the treatment plan depends heavily on where the cancer is and how far it has traveled. This cancer forms in the tiny tubes inside the kidneys that filter blood and make urine. In many cases, people don’t notice symptoms early on, and doctors find tumors during imaging tests done for other reasons. When symptoms do appear, they might include blood in the urine, pain in the sides or back, a lump in the belly, fever, night sweats, or unexplained weight loss.^[1]

The main goal of treating renal cell carcinoma is to remove or destroy cancer cells, slow down disease progression, relieve symptoms, and help patients maintain the best possible quality of life. Treatment success depends on multiple factors, including the size and location of the tumor, whether cancer has spread beyond the kidney, the specific type of kidney cancer cells involved, and the patient’s overall health and kidney function. For early-stage disease confined to the kidney, treatment often aims for a cure. When cancer has spread to other parts of the body, treatment focuses on controlling the disease for as long as possible and managing symptoms that affect daily life.^[4]

Medical organizations have developed standard treatment guidelines based on decades of research and patient outcomes. At the same time, scientists continue to test new therapies in clinical trials, searching for more effective ways to fight kidney cancer. These research studies evaluate experimental drugs and treatment combinations that may one day become standard care. Understanding both established treatments and emerging options can help patients and their families make informed decisions about care.^[11]

Standard Treatment Approaches

Surgery as Primary Treatment

Surgery remains the cornerstone of treatment for renal cell carcinoma that hasn’t spread beyond the kidney. The most common surgical procedure is called a nephrectomy, which means removing part or all of the affected kidney. There are two main types of nephrectomy. A partial nephrectomy removes only the tumor and some surrounding tissue, leaving the rest of the kidney intact. A radical nephrectomy removes the entire kidney, often along with nearby structures like the adrenal gland and lymph nodes.^[14]

Surgeons can perform nephrectomy in two different ways. Open surgery involves making one large incision in the abdomen, under the ribs, or in the back. Laparoscopic surgery, also called minimally invasive surgery, uses several small incisions and a long tube with a tiny camera to view inside the body. The choice between these approaches depends on tumor characteristics, cancer stage, and the patient’s physical condition. Most people can live normally with one healthy kidney, though careful monitoring may be needed afterward.^[12]

Even when cancer has already spread to other organs, surgery to remove the kidney tumor may still be helpful. Removing the primary tumor can sometimes make other treatments work better. The decision to proceed with surgery in advanced cases requires careful discussion between patient and doctor about potential benefits and risks.^[14]

Targeted Therapy Medications

Targeted therapies are medicines that attack specific molecules on or inside cancer cells. Unlike traditional chemotherapy, which often affects all rapidly dividing cells in the body, targeted therapies focus on particular proteins that help cancer cells grow, divide, and spread. This more precise approach can be effective while causing different side effects than chemotherapy.^[14]

Most targeted therapies used for renal cell carcinoma work in one of two ways. Some block the process by which new blood vessels grow to feed the tumor. Tumors need a blood supply to get oxygen and nutrients, so cutting off this supply can slow or stop cancer growth. These drugs target pathways involving vascular endothelial growth factor (VEGF) and its receptors. Other targeted therapies block specific proteins inside cancer cells that signal them to multiply. These include drugs that inhibit enzymes called tyrosine kinases or block a protein complex called mTOR.^[5]

Several targeted therapy drugs have received approval for treating kidney cancer. Some common brand names include Sutent, Inlyta, Cabometyx, and Afinitor. Doctors prescribe these medications as pills taken by mouth, usually daily. Treatment continues as long as the cancer responds and side effects remain manageable. Side effects can include fatigue, high blood pressure, diarrhea, hand-foot syndrome (redness and pain on palms and soles), loss of appetite, and changes in blood counts. Close monitoring helps doctors adjust doses or switch medications if side effects become severe.^[14]

Immunotherapy

Immunotherapy harnesses the body’s own immune system to fight cancer. The immune system normally protects against infections and disease, but cancer cells can hide from immune attack. Immunotherapy drugs help the immune system recognize and destroy cancer cells. This treatment approach has revolutionized care for advanced kidney cancer in recent years.^[15]

The most commonly used immunotherapies for renal cell carcinoma are called checkpoint inhibitors. These drugs work by blocking proteins that prevent immune cells from attacking cancer. When these “brakes” on the immune system are released, immune cells called T-cells can better recognize and kill cancer cells. Checkpoint inhibitors used for kidney cancer include drugs that target the PD-1/PD-L1 pathway or CTLA-4 protein. Brand names include Opdivo (nivolumab), Keytruda (pembrolizumab), Bavencio (avelumab), and Yervoy (ipilimumab).^[15]

These medications are given through a vein (intravenously) at regular intervals, typically every few weeks. Treatment schedules vary depending on the specific drug. Many patients receive immunotherapy as a first-line treatment for advanced kidney cancer, either alone or combined with another immunotherapy or a targeted therapy drug. Studies show that combination approaches often work better than single drugs for certain patients.^[14]

Immunotherapy side effects differ from those of targeted therapy or chemotherapy. Because these drugs boost immune system activity, they can cause the immune system to attack normal organs and tissues. This leads to inflammation that can affect the intestines, liver, lungs, hormone-making glands, skin, or other organs. Common side effects include fatigue, rash, diarrhea, and loss of appetite. More serious immune-related side effects require prompt medical attention and may need treatment with steroids to calm the immune response.^[15]

Other Treatment Methods

For patients who cannot undergo surgery due to health reasons or tumor location, other options may be available. Ablation therapy destroys tumors using extreme temperatures. Radiofrequency ablation uses heat, while cryoablation uses extreme cold to freeze cancer cells. A probe is inserted through the skin directly into the tumor, guided by imaging scans. These techniques work best for smaller tumors.^[14]

Radiation therapy uses high-energy beams to kill cancer cells. While not commonly used for the primary kidney tumor itself, radiation can be very effective for treating kidney cancer that has spread to bones or the brain. It helps relieve pain and other symptoms caused by tumors in these locations. A specialized type called stereotactic body radiotherapy (SBRT) delivers precise, high-dose radiation and shows promise in some kidney cancer cases.^[3]

Another procedure called renal artery embolization blocks blood flow to the kidney tumor. A catheter is threaded through blood vessels to the artery feeding the tumor, then materials are injected to block the vessel. This can shrink tumors before surgery or help control symptoms when surgery isn’t possible.^[5]

Treatment Being Tested in Clinical Trials

Clinical trials test new treatments or new ways of combining existing treatments to find better options for patients with renal cell carcinoma. These research studies follow strict scientific and ethical standards to protect participants while gathering information about promising therapies. Trials are conducted in phases, each with a specific purpose.^[4]

Phase I trials test a new drug or treatment for the first time in a small group of people. The main goal is to evaluate safety, determine safe dosage ranges, and identify side effects. Phase II trials give the treatment to a larger group to further assess safety and begin evaluating whether it works. Phase III trials compare the new treatment to standard therapy in large groups of patients to confirm effectiveness, monitor side effects, and collect information about how to use it safely. Some trials also test treatments after surgery to prevent cancer from returning, called adjuvant therapy.^[14]

Novel Immunotherapy Approaches

Researchers continue developing new immunotherapy strategies beyond checkpoint inhibitors. Some studies test combinations of different checkpoint inhibitors together to see if blocking multiple immune pathways produces better results. Early findings suggest that combining drugs targeting PD-1 with those targeting CTLA-4 can lead to stronger anti-tumor responses in some patients, though side effects may also increase.^[15]

Scientists are also investigating ways to help the immune system better recognize kidney cancer cells. Some experimental approaches involve vaccines designed to train immune cells to attack specific proteins found on cancer cells. Others modify a patient’s own immune cells in the laboratory to make them more effective cancer fighters, then return these enhanced cells to the patient’s body. These cell-based therapies represent cutting-edge approaches still in early research phases.^[15]

Combination Strategies

Many clinical trials now test combinations of immunotherapy with targeted therapy drugs. The rationale is that these treatments work through different mechanisms and together might be more effective than either alone. Several combination regimens have shown promise in recent trials and some have already received regulatory approval based on strong results.^[14]

For example, trials have tested combining checkpoint inhibitors like nivolumab or pembrolizumab with VEGF-targeting drugs like axitinib or cabozantinib. Results from large phase III studies showed that these combinations helped patients live longer without their cancer worsening compared to standard single-drug treatment. Side effects from combinations require careful management, as patients may experience toxicities from both types of drugs.^[15]

New Targeted Drugs

Researchers continue developing new targeted therapy drugs that attack different molecular pathways involved in kidney cancer growth. One promising area involves drugs that block HIF-2 alpha, a protein that accumulates in clear cell kidney cancer cells due to loss of the VHL gene. A drug called belzutifan targets this protein and has shown encouraging results in clinical trials, particularly for patients with von Hippel-Lindau disease who develop multiple kidney tumors.^[5]

Other experimental drugs target different proteins or pathways that cancer cells use to survive and grow. These include inhibitors of molecules involved in cell metabolism, DNA repair, or immune evasion. Each new drug undergoes careful testing to determine which patients are most likely to benefit and what side effects may occur.^[14]

Adjuvant and Neoadjuvant Treatment

Clinical trials are testing whether giving immunotherapy or targeted therapy after surgery can prevent cancer from coming back. This adjuvant approach aims to eliminate any remaining cancer cells that might cause recurrence. Some trials have shown that certain immunotherapies given after surgery can reduce the risk of recurrence in patients with high-risk features.^[14]

Other studies investigate neoadjuvant treatment, meaning therapy given before surgery. The goal is to shrink tumors, making them easier to remove and potentially improving surgical outcomes. This approach also provides information about how well the cancer responds to treatment, which can guide decisions about additional therapy after surgery.^[14]

Where Trials Are Conducted

Clinical trials for renal cell carcinoma take place at cancer centers, universities, and hospitals around the world. Major cancer institutions in the United States, Europe, and other regions actively enroll patients in kidney cancer studies. Patients interested in participating should discuss options with their oncologist, who can help identify appropriate trials based on cancer stage, previous treatments, and other eligibility criteria.^[4]

Eligibility requirements vary by study but typically include factors like cancer type and stage, previous treatments, kidney function, overall health status, and sometimes specific genetic features of the tumor. Some trials focus on patients who haven’t received treatment yet, while others enroll people whose cancer has progressed despite prior therapy. Participation in clinical trials gives patients access to new treatments while contributing to medical knowledge that may help future patients.^[14]

Most Common Treatment Methods

• Surgery (Nephrectomy)
  • Partial nephrectomy removes only the tumor and surrounding tissue while preserving the rest of the kidney
  • Radical nephrectomy removes the entire kidney, sometimes with nearby structures like the adrenal gland and lymph nodes
  • Can be performed as open surgery with one large incision or laparoscopic surgery using several small incisions
  • Most people function normally with one healthy kidney after surgery
  • May be helpful even when cancer has spread, as removing the primary tumor can improve other treatments’ effectiveness
• Targeted Therapy
  • Medicines that attack specific molecules and proteins on or inside cancer cells
  • VEGF inhibitors block new blood vessel growth that feeds tumors
  • Tyrosine kinase inhibitors block proteins that signal cancer cells to multiply
  • mTOR inhibitors target a protein complex involved in cell growth
  • Given as oral pills, usually taken daily for as long as the cancer responds
  • Common drugs include sunitinib, axitinib, cabozantinib, and everolimus
• Immunotherapy
  • Checkpoint inhibitors release brakes on the immune system so it can attack cancer cells
  • Drugs targeting PD-1/PD-L1 pathway include nivolumab, pembrolizumab, and avelumab
  • CTLA-4 inhibitor ipilimumab is used in combination approaches
  • Given intravenously every few weeks
  • Often combined with other immunotherapy drugs or targeted therapy for better results
  • Side effects relate to increased immune system activity and may affect various organs
• Ablation Therapy
  • Radiofrequency ablation uses heat to destroy tumor tissue
  • Cryoablation uses extreme cold to freeze cancer cells
  • A probe is inserted through the skin into the tumor, guided by imaging
  • Works best for smaller tumors when surgery is not an option
• Radiation Therapy
  • Uses high-energy beams to kill cancer cells
  • Commonly used for kidney cancer that has spread to bones or brain
  • Helps relieve pain and symptoms from metastatic tumors
  • Stereotactic body radiotherapy delivers precise, high-dose radiation to targeted areas
• Clinical Trial Therapies
  • Novel checkpoint inhibitor combinations for stronger immune responses
  • Combination strategies pairing immunotherapy with targeted therapy drugs
  • New targeted drugs like HIF-2 alpha inhibitors for specific cancer types
  • Adjuvant immunotherapy given after surgery to prevent recurrence
  • Neoadjuvant treatment before surgery to shrink tumors