Types of Treatment for Kidney Cancer

Executive Summary

Treatment (kidney cancer) recommendations depend upon the size, grade and type of tumor, metastasis, possible side effects, and patient’s preferences and overall health. The standard treatment techniques used to treat kidney cancers are Surgery and various Systemic Therapies (Chemotherapy, Targeted therapy or immunotherapy) using medication. Active surveillance is beneficial in older adults and people with a tiny renal tumour and other primary medical conditions, such as heart disease, chronic kidney disease, or severe lung disease.

The other standard treatment for kidney cancer includes surgery (Radical nephrectomy, Partial nephrectomy, and Laparoscopic and robotic surgery), non-surgical treatment (Radiofrequency ablation, and Cryoablation), therapies using medication (using an intravenous (IV) tube to administer medication into the vein using a needle, and capsule or pill administered orally), systemic therapies (chemotherapy, immunotherapy and targeted therapy), chemotherapy (combination of gemcitabine (Gemzar) with capecitabine (Xeloda) or fluorouracil (5-FU)), targeted therapy (Anti-angiogenesis therapy, Tyrosine kinase inhibitors, mTOR inhibitors, HIF2a inhibitor, and combined therapies), immunotherapy (Interleukin-2 (IL-2), Alpha-interferon, Immune checkpoint inhibitors), and radiation therapy. Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies.

Treatment of Kidney Cancer

A multidisciplinary approach is required to treat any form of kidney cancer. The treatment will include the involvement of different doctors and other healthcare members (called the multidisciplinary team) and will use different treatment strategies. They will care for and evaluate the patient before and throughout the treatment period.

The health care team will include the following specialists:

Urologist: A genitourinary tract specialist who specialises in the kidneys, bladder, genitals, prostate, and testicles.

Urologic oncologist: A urologist who specialises in treating urinary tract malignancies.

Medical oncologist: A doctor who has been trained to treat cancer with medication-based systemic therapy.

Radiation oncologist: Oncologist who specialises in radiation therapy. A doctor who specialises in using radiation therapy to treat cancer. This doctor will be a part of the team if radiation therapy is recommended.

Besides these people, cancer care includes a variety of other health care professionals like nurse practitioners, physician assistants, pharmacists, counsellors, dieticians, social workers and many more others. All these people come together to devise a treatment plan as suiting the patient’s cancer condition. The team will design a comprehensive treatment plan by evaluating the patient’s disease condition and overall health. 

How kidney cancer is treated

Kidney cancer treatment focuses on eliminating cancer growth and preserving the functions of nearby tissues, organs, and nerves. While planning the treatment strategy, the healthcare team will consider how the treatment will affect the patient’s quality and comfort of life. 

The standard treatment techniques used to treat kidney cancers are Surgery and various Systemic Therapies (Chemotherapy, Targeted therapy or immunotherapy) using medication ​1​. The treatment plan will also focus on managing and relieving symptoms, signs and side effects, which forms an essential part of cancer treatment.

Treatment options and plans are designed based on several factors like the type of kidney cancer, its stage and grade, probable side effects, the patient’s preferences, choices and overall health condition. Patients should take time to learn about all the available treatment options and be sure to ask questions and clear doubts about things that are unclear and appears complex. Ask your doctor about the aim of each treatment and what outcome you can expect while receiving the treatment. This is what is called “shared decision making.” Shared decision making helps the patients to have informed choices regarding treatment. This will help the healthcare team choose and plan a treatment strategy that best fits your aims and expectations.

ACTIVE SURVEILLANCE

The doctor may advise that the tumour be closely monitored with regular diagnostic testing and clinic visits. “Active surveillance” is the term for this. Active surveillance is beneficial in older adults and people with a tiny renal tumour and another major medical condition, such as heart disease, chronic kidney disease, or severe lung disease. Even if cancer has spread to other parts of the body, active surveillance may be utilised for some people with kidney cancer if they are otherwise healthy and have little or no symptoms. If the condition is progressing, systemic therapy can be initiated.

Active monitoring is not the same as “watchful waiting for kidney cancer.” Regular appointments to discuss symptoms are required under watchful waiting, but patients are not subjected to routine diagnostic testing such as biopsies or imaging scans. The doctor merely keeps an eye out for signs and symptoms. A new treatment plan is explored if symptoms indicate that action is required.

Following are the treatment strategies used to treat kidney cancers:

SURGERY

A Surgery is a procedure where the tumour and some surrounding healthy tissues are removed via an operation. Surgery is one of the best treatments for treating and destroying kidney cancers. Surgery to remove the tumor may be the only treatment needed if cancer has not progressed or metastasised beyond the kidneys. During surgery, part or all of the kidney and adjacent tissue and lymph nodes may be removed to eliminate the tumor. There are different types of surgical procedures for treating kidney cancers. They include ​2​:

  • Radical nephrectomy: a surgical procedure that removes the tumor, the entire kidney, and the surrounding tissue. Radical nephrectomy and lymph node dissection are required if the disease has spread to neighboring tissue and lymph nodes. The cancer-affected lymph nodes are removed during a lymph node dissection. If cancer has spread to the adrenal gland or surrounding blood vessels, the surgeon will remove the adrenal gland and sections of the blood arteries during adrenalectomy. Radical nephrectomy is usually recommended when there isn’t much good tissue left after a huge tumor. The renal tumor may develop directly inside the renal vein and enter the vena cava on its route to the heart. Complex cardiovascular surgical techniques will be required if this occurs.
  • Partial nephrectomy: The tumor is surgically removed in partial nephrectomy. After this sort of surgery, kidney function is preserved, and the risk of developing a chronic renal disease is reduced. Research has shown that partial nephrectomy is beneficial for treating T1 tumors whenever surgery is not possible. Newer surgical techniques that use a smaller surgical incision or cut have been linked to fewer adverse effects and a quicker recovery.
  • Laparoscopic and robotic surgery: these are minimally invasive surgery. During laparoscopic surgery, the surgeon makes multiple minor cuts in the belly instead of a single bigger cut as in traditional surgery. The surgeon then uses telescopic tools to entirely remove the kidney or perform a partial nephrectomy through these microscopic keyhole wounds. The surgeon may employ robotic devices to execute the procedure in some cases. This procedure may take longer, but it is likely to be less painful. The use of laparoscopic and robotic techniques necessitates specialized training. It’s crucial to talk to your surgical team about these procedures’ potential benefits and hazards and ensure that they’ve experienced doing the procedure.

Patients must enquire about the type of surgery necessary to remove the cancer growth and the associated side effects to their healthcare team.

NON-SURGICAL TREATMENTS

Surgery is not always recommended because of the tumor’s features or the patient’s overall health. To determine if these treatments are appropriate and safe for them, each patient should fully discuss their diagnosis and risk factors with their doctor. Following are some other methods to treat kidney tumors:

  • Radiofrequency ablation: The use of a needle put into the tumor to eliminate the malignancy with an electrical current is known as radiofrequency ablation (RFA) ​3​. An interventional radiologist or urologist performs the procedure. The patient is sedated and given a local anaesthetic to numb the area. RFA was previously reserved for patients who were too ill to undergo surgery. The majority of these patients are now under active surveillance.
  • Cryoablation: The freezing of cancer cells with a metal probe inserted through a small incision is known as cryoablation, sometimes known as cryotherapy or cryosurgery. The malignant tissue is probed with a metal probe. A CT scan and ultrasonography guide the probe. An interventional radiologist performs the treatment, which requires general anaesthesia for many hours. Some surgeons use this procedure in conjunction with laparoscopy to treat the tumour, but there isn’t any long-term study to back it up.

THERAPIES USING MEDICATION

Treatments using medications are used to eliminate cancer cells. Such therapies are called systemic therapy. Systemic therapy refers to medication or drugs to eliminate cancer cells. These drugs or medicines are administered through the bloodstream to reach tumour growths or cells throughout the body. Medicated therapies can also be administered to the patient’s body locally, where the medication or drug is applied directly on the tumour or is kept in a single part of the body.

A medical oncologist usually prescribes such therapies. Systemic therapies are commonly given in two ways:

  • Using an intravenous (IV) tube to administer medication into the vein using a needle.
  • A capsule or pill that is swallowed or administered orally.

The systemic therapies used to treat kidney cancers are Chemotherapy, Immunotherapy and Targeted Therapy. A patient may receive one of these, or sometimes a combination of both, administered simultaneously. Systemic therapies can also be given as part of the overall treatment plan, including surgery or radiation.

Many studies focus on developing efficient medications that can help treat and cure cancer. Patients are encouraged to talk with their doctor about the prescribed medicines and learn and understand more about them. Ask them questions regarding the purpose, possible side effects of the drugs, and their possible interactions with other treatments and medications. One should also let their doctor know about any additional treatment or medicines they are taking well before cancer treatment. This is because certain drugs and herbs can interact with cancer medications and can cause complications.

Chemotherapy

Chemotherapy or chemo procedure refers to drugs or medications to eliminate cancer cells. These drugs operate by preventing the cancer cells from growing, dividing and generating more cells. A chemo regimen generally consists of several cycles given over a period of time. A patient may receive a single type of drug or a combination of different medications, all given simultaneously.

Chemotherapy is effective in treating various cancers, but most cases of kidney cancer are resistant to it ​4​. Researchers are still looking at new drugs and pharmacological combinations. The combination of gemcitabine (Gemzar) with capecitabine (Xeloda) or fluorouracil (5-FU) can temporarily reduce a tumor in some people.

It’s vital to remember that transitional cell carcinoma, also known as urothelial carcinoma, and Wilms tumour are far more likely to respond to chemo treatment.

Chemotherapy can cause side effects, and these depend on the dose of medication used and the individual’s overall health. But common side effects include nausea and vomiting, hair loss, fatigue, loss of appetite, risk of infection, and diarrhoea. These side effects are likely to vanish after the treatment is finished.

Targeted therapy

Targeted therapy refers to a systemic treatment that targets specific genes, proteins of the cancer cells and the surrounding tissue that contributes to tumour growth and proliferation. This therapy shuns cancer’s development and metastatic capability by causing very little damage to the surrounding healthy cells. 

The targets of each tumour differ. The doctor will run various tests or scans to identify the tumour’s proteins, genes, and other characteristic features to choose the suitable treatment option. This helps the doctor to implement the most effective treatment. Many types of research are happening in this field, too, to devise better target therapy options.

Targeted therapies used to treat kidney cancer is as follows ​5​:

  • Anti-angiogenesis therapy: Angiogenesis is the process of forming new blood vessels, and this type of treatment aims to inhibit it. Most clear cell kidney tumours contain VHL gene mutations, which cause the malignancy to produce excessive amounts of a protein called vascular endothelial growth factor (VEGF). VEGF is a protein that regulates the creation of new blood vessels and can be inhibited by certain medicines. Anti-angiogenesis therapies aim to “starve” a tumour of nutrients given by blood vessels, which are required for it to develop and spread. Small chemical inhibitors of the VEGF receptors (VEGFR) or antibodies directed against these receptors are two strategies to block VEGF.

For persons with metastatic renal cell carcinoma, an antibody called bevacizumab (Avastin) has been found to suppress tumour growth. Bevacizumab, in combination with interferon, inhibits tumour growth and spread. The U.S. Food and Drug Administration (FDA) has approved two identical medications for the treatment of metastatic kidney cancer: bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev). These are referred to as biosimilars, and they work in a similar way to the original bevacizumab antibody.

Tyrosine kinase inhibitors are another technique to block VEGF (TKIs). TKIs that block VEGF receptors include axitinib (Inlyta), cabozantinib (Cabometyx), pazopanib (Votrient), lenvatinib (Lenvima), sorafenib (Nexavar), sunitinib (Sutent), and tivozanib (Fotivda). They could be utilised to treat kidney carcinoma with clear cells. TKIs can cause diarrhoea, elevated blood pressure, and pain and sensitivity in the hands and feet, among other things. Pazopanib, sunitinib, and cabozantinib are three of the authorised medications frequently utilised as first-line treatments. Axitinib or cabozantinib could be utilised with immunotherapies as a first-line treatment (see below). They may be recommended if axitinib, cabozantinib, lanvatinib, and tivozanib have not been utilised after first-line treatment.

  • mTOR inhibitors: Everolimus (Afinitor) and temsirolimus (Torisel) are medications that target mTOR, a protein that aids in the growth of kidney cancer cells. These medications have been shown in studies to slow kidney cancer progression.
  • HIF2a inhibitor: Belzutifan (Welireg) is a medication that inhibits the growth of blood vessels and cancer cells by inhibiting the protein hypoxia-inducible factor-2 alpha (HIF2a). Belzutifan is a drug that can treat von Hippel-Lindau syndrome patients with renal cell carcinoma.
  • Combined therapies: The FDA approved two combination therapies for advanced renal cell carcinoma for the first time in 2019. Axitinib and pembrolizumab (Keytruda), an immune checkpoint inhibitor, make the first combination. Axitinib and avelumab (Bavencio), an immune checkpoint inhibitor, are used in the second combination. Axitinib is an angiogenesis inhibitor. Both pembrolizumab and avelumab engage the immune system to fight cancer cells by targeting the PD-1 pathway.

The FDA approved two more combination treatments for advanced renal cell carcinoma in 2021: cabozantinib (an anti-angiogenesis therapy) with nivolumab (an immune checkpoint inhibitor blocking the PD-1 pathway) and lenvatinib (also an anti-angiogenesis therapy) with pembrolizumab (an immune checkpoint inhibitor blocking the PD-1 pathway). People who take this treatment will not be screened for PD-L1 because these treatment combinations operate independently of whether the tumour expresses the PD-L1 protein. While these medicines have been approved based on better results than sunitinib, none of the combinations has been directly compared. As a result, based on each patient’s specific situation, the doctor will select the most appropriate treatment approach.

Talk with your healthcare team regarding the possible side effects of such medicated therapies and in what ways they could be prevented, managed and relieved.

Immunotherapy

Immunotherapy is also called biologic therapy. The medicated treatment focuses on improving the body’s natural defences to fight and destroy cancer growth. This therapy uses materials made either naturally by the body or in a lab to improve, target or restore the functions of the immune system.

  • Interleukin-2 (IL-2): is a kind of interleuk (IL-2, Proleukin). IL-2 is immunotherapy utilised to treat kidney cancer in its latter stages. It’s a protein produced by white blood cells called a cytokine. It plays a role in immune system function, including tumour cell killing.

Low blood pressure, extra fluid in the lungs, renal damage, heart attack, haemorrhage, chills, and fever are serious side effects of high-dose IL-2. During therapy, patients may be required to stay in the hospital for up to ten days. Some symptoms, however, may be reversible. Only clinics with experience treating kidney cancer with high-dose IL-2 should recommend it. A tiny percentage of persons with metastatic kidney cancer can be cured with high-dose IL-2. Low-dose IL-2 is used in some institutions because it has fewer adverse effects, although it is less effective.

  • Alpha-interferon: Alpha-interferon is used to treat kidney cancer that has spread. Interferon appears to change the proteins on the surface of cancer cells and slow their growth. Although it has not proven to be as beneficial as IL-2, alpha-interferon has been shown to lengthen lives compared with an older treatment called megestrol acetate (Megace).
  • Immune checkpoint inhibitors: Immune checkpoint inhibitors, a kind of immunotherapy, are being researched in kidney cancer. The FDA has authorised the following immune checkpoint inhibitor therapies for kidney cancer:
  • For specific individuals with advanced renal cell carcinoma who have not previously been treated, nivolumab (Opdivo) and ipilimumab (Yervoy) are used.
  • As a first-line treatment for advanced renal cell carcinoma, nivolumab combined with cabozantinib.
  • The combination of avelumab (Bavencio) with axitinib as a first-line treatment for advanced renal cell carcinoma.
  • People with advanced renal cell carcinoma should receive pembrolizumab (Keytruda) plus axitinib as a first-line treatment.
  • For persons with advanced renal cell carcinoma, pembrolizumab plus lenvatinib is used as a first-line treatment.
  • Pembrolizumab alone is associated with an increased risk of recurrence after nephrectomy or surgical excision of metastatic sites.

Extensive clinical trials comparing the immunotherapy combinations to sunitinib in persons with advanced or metastatic kidney cancer led to advanced renal cell carcinoma approvals. Additional studies had previously shown that nivolumab, administered as a single dose through the vein every two weeks, helped those who had previously undergone anti-angiogenesis treatments live longer than patients treated with the targeted therapy everolimus. Pembrolizumab was approved after surgery after a large clinical trial indicated an improvement in time to recurrence for persons who had surgery for the original kidney tumour or all sites of distant metastasis. Several clinical trials involving immune checkpoint inhibitors for the treatment of kidney cancer are currently underway.

Different types of immunotherapies can cause various side effects. Common side effects of the procedure include flu-like symptoms, skin reactions, weight changes and diarrhoea. Talk with your healthcare team or doctor regarding the possible side effects of the immunotherapy procedure recommended for you. 

RADIATION THERAPY

The use of high-energy x-rays or other particles to eliminate cancer cells is known as radiation therapy. A radiation oncologist is a doctor who specialises in treating cancer patients with radiation therapy.

As a first-line treatment for kidney cancer, radiation therapy is ineffective. Because of the harm it does to the healthy kidney, and it is rarely used alone to treat kidney cancer. Only if a patient is unable to have surgery is radiation therapy utilised. Even then, it is usually only in places where cancer has progressed rather than on the underlying kidney tumour. When cancer has spread, radiation therapy is usually employed. This is done to aid with symptoms like bone pain and brain swelling.

Physical, emotional, and social effects of kidney cancer

Cancer can cause many physical, emotional and social effects. Cancer care doesn’t end with active treatment. Post-treatment care is as critical as active treatment. Palliative or supportive care focus on managing and relieving symptoms and side effects associated with cancer treatment. Palliative care is carried out along with an active treatment strategy, which helps in improving the treatment efficiency by slowing the cancer growth or destroying it.

Palliative care focuses on improving a patient’s condition by helping them to manage and relieve symptoms. The care extends support not just to the patients but also to their loved ones. It also focuses on the non-medical needs of cancer patients, like managing finances. Palliative care is independent of the age, cancer stage or type of patient. Palliative care works best when it is begun right after a cancer diagnosis. This helps prevent the cancer condition and its symptoms and side effects from aggravating. Palliative focuses on improving the comfort and quality of a patient’s life. Palliative care enhances the effectiveness of active treatment. Sometimes a patient may receive chemotherapy, surgery or radiation therapy as palliative care.  

Patients should talk with their health care team about the aim of each treatment option, about the probable side effects and the available palliative care options before the active treatment begins.

The health care team will enquire about your medical history, symptoms and side effects during treatment. Be sure to communicate whatever you are feeling to the doctor. This helps them treat any symptoms or side effects that you are experiencing with ease. This will eventually help prevent your condition from becoming worse. 

Metastasis of kidney cancer

Metastatic cancer refers to cancer or tumour that spreads from its origin to different body parts. If you are experiencing any signs or symptoms related to cancer metastasis, communicate it with your doctor. The doctor or the health care team will develop an active treatment plan to cure this condition. One can also go for clinical trial options. 

Metastasis can occur even after active treatment and removal of the cancer growth. Hence it can be stressful for the patient and their loved ones to bear the diagnosis. So, patients and their loved ones are encouraged to have active communication with the doctor, nurses, social workers or counsellors regarding how they are feeling. Patients can also talk with other cancer survivors or join a support group.

Remission and the chance of Cancer Recurrence

Remission refers to a stage where there are no signs or symptoms of cancer in the body. The condition can be called NED or “no evidence of disease” in the body. Remission can be permanent or temporary. Cancer patients in remission are constantly worried about a probable cancer recurrence. Patients must continue tests, scans, physical examinations even after successful treatment to look for recurrence. Talk with your doctor about the chance of the cancer condition recurring back in your body. If cancer recurs in the same place as before, it is called local recurrence, and if it happens nearby the origin point, it is called a regional recurrence. If it recurs in some distant place in the body, it is called distant recurrence.

What If the treatment does not work?

Cancer recovery may not be successful at times. The disease condition is advanced or terminal if it cannot be controlled or cured. Any stage of cancer can be stressful to people. A diagnosis that states an advanced, aggressive tumour can cause even more stress and make people hopeless and uncertain about their lives. Patients should have open, honest communications with their doctor or health care team about their concerns, feelings and preferences. Health care team members are skilled and will support the patients and their caregivers. They will focus on improving the comfort and quality of the patient’s life by providing them physical, mental and financial support.

People diagnosed with advanced cancer and the expected chance of survival is for less than six months can consider hospice care. Hospice care focuses on providing the best possible quality care for patients whose survival chance is low. Patients and their families can talk to the health care team about the available hospice options, including a unique hospice centre, hospice care at home or any other health care location. People can also avail nursing care options.

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