Kidney Cancer Treatment & Diagnosis in Singapore

Sometimes, the doctor may recommend close monitoring of the tumour through regular diagnostic tests and clinic appointments. Active surveillance is a form of treatment for localised kidney cancer in which the doctor actively monitors the tumour. Active surveillance is generally recommended for older adults and people who have a small renal tumour and other serious medical conditions, such as heart disease, chronic kidney disease, or severe lung disease. It may also be recommended if surgery is not the best option for the patient and if the patient has a tumour in their kidney that is smaller than four (4) centimetres. Sometimes, a biopsy may be conducted before deciding to watch the tumour to see if the lump is really cancerous.

Surgery is usually the main and most common treatment for kidney cancer, which may potentially help cure the cancer itself.

If the cancer has not spread beyond the kidneys, surgery to remove the tumour may be the only treatment needed. However, in some cases, the surgery may also involve removing part or all of the kidney, as well as surrounding tissue and lymph nodes.

The different types of surgery include the following procedures:

• Radical Nephrectomy: Surgery to remove the tumour, the entire kidney, and surrounding tissue is called a radical nephrectomy. In this operation, the surgeon may make the incision in several places, with the most common site being the belly (or the middle of the abdomen), under the ribs on the same side of the tumour, or in the back at the position of the kidney.

If nearby tissue and surrounding lymph nodes are also affected by the disease, a radical nephrectomy and lymph node dissection may be performed. During a lymph node dissection, the lymph nodes affected by the cancer are removed. If the cancer has spread to the adrenal gland or nearby blood vessels, the surgeon may remove the adrenal gland during a procedure called an adrenalectomy, as well as parts of the blood vessels.

A radical nephrectomy is usually recommended to treat a large tumour when there is not much healthy tissue remaining. Sometimes, the renal tumour will grow directly inside the renal vein and enter the vena cava; the large vein that empties into the heart. If this happens, complex cardiovascular surgical techniques may be required.

• Partial Nephrectomy: A partial nephrectomy is the surgical removal of the tumour. This type of surgery preserves kidney function and lowers the risk of developing chronic kidney disease after surgery. As with a radical nephrectomy, the surgeon can make the incision in several places, depending on factors like the location of the tumour.

Partial nephrectomy is the most common treatment for patients with early-stage kidney cancer. It is often done to remove single small tumours that are less than four (4) centimetres or remove large tumours up to seven (7) centimetres across the kidney. One of the benefits of partial nephrectomy is that the patient gets to retain more kidney function. However, this particular surgery may not be an option if the tumour is in the middle of the kidney, large, has spread to the surrounding lymph nodes or organs or if there is more than one tumour in the same kidney.

• Laparoscopic and Robotic Surgery (minimally invasive surgery): In a laparoscopic surgery, the surgeon makes several small cuts in the abdomen, rather than the one larger cut used during a traditional surgical procedure. The surgeon then inserts telescoping equipment into these small keyhole incisions to completely remove the kidney or perform a partial nephrectomy. Sometimes, the surgeon may use robotic instruments to perform the operation. This surgery may take longer but may be less painful.

Radiation therapy involves the use of high-energy rays to potentially destroy cancer cells. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time.

Radiation therapy is not effective as a primary treatment for kidney cancer. It is also very rarely used alone because of the damage it causes to the healthy kidney. For most patients with kidney cancer, radiation therapy is more often used to control or reduce symptoms that have spread to other areas of the body, such as the bones and brain, or when a patient has only one kidney.

Radiation therapy also includes External beam therapy (EBRT) and Stereotactic Body Radiation Therapy (SBRT).  EBRT focuses radiation on the cancer from a source outside the body while SBRT treats a single area of cancer spread. However, other treatments are generally prescribed before introducing radiation therapy as part of the patient’s treatment plan.

Chemotherapy is not a standard treatment for patients as the cancer cells do not usually respond well to chemotherapy.

Immunotherapy, also called biologic therapy, is designed to boost the body’s natural defences to fight cancer. It uses materials made either by the body or in a laboratory to improve, target, or potentially restore immune system function, such as:

• Interleukin-2 (IL-2, Proleukin): IL-2 is a type of immunotherapy that has been used to treat advanced stage kidney cancer. It is a cytokine, which is a protein produced by white blood cells. It plays an important role in the immune system, including the destruction of tumour cells.

• PD-1 Inhibitors: Another form of immunotherapy treatment is PD-1 inhibitor. Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are drugs that target PD-1, a checkpoint protein on immune system cells called T cells, that normally helps keep these cells from attacking normal cells in the body. By blocking PD-1, this drug boosts the immune response against cancer cells. It has shown promising results in shrinking or slowing down the growth of kidney cancer tumours.

Pembrolizumab may be given for one (1) year after surgery for patients who have a higher risk of relapsing. It may also be given to patients who underwent surgery to remove the main tumour along with surgery to remove any organs or lymph nodes of the cancer spread. Pembrolizumab is usually given with targeted drugs Axtinib or Lenvatinib as the first treatment for patients with advanced stage kidney cancer.

For patients with an intermediate or poor risked advanced stage kidney cancer who have not received any form of treatment, nivolumab can be given with ipilimumab (a CTLA-4 inhibitor) for four (4 doses) followed by nivolumab alone. This combination has been shown to help people live longer (see CTLA-4 inhibitors below). Nivolumab can also be used for patients whose advanced kidney cancer starts growing again after targeted drug treatments. Studies have shown that this therapy may help patients live longer.

Pembrolizumab is given as an intravenous (IV) infusion every three (3) or six (6) weeks, while Nivolumab is given as an intravenous (IV) infusion every two (2), three (3) or four (4) weeks.

• PD-L1 Inhibitors: Immunomodulators such as Avelumab (Bavencio) is a checkpoint inhibitor that targets the PD-1/PD-L1 pathway. This is commonly prescribed to patients with advanced kidney cancer as a first line of therapy in combination with chemotherapy.

Blocking the PD-L1 protein can help boost the immune response against cancer cells which may help to shrink some tumours or slow their growth. It is given every two (2) weeks as an IV infusion.

• CTLA-4 Inhibitors: This is another drug that boosts immune response, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check. For patients with intermediate or poor risk advanced kidney cancer who have not received any treatment, ipilimumab can be given with nivolumab (a PD-1 inhibitor) for four (4) doses followed by nivolumab alone.

Ipilimumab is given as an intravenous (IV) infusion, usually once every three (3) weeks for four (4) treatments.

Targeted drug therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Targeted drug therapy is commonly used to treat advanced kidney cancer. This type of treatment blocks the growth and spread of cancer cells and potentially limits damage to healthy cells.

As not all tumours have the same targets, research studies continue to find out more about specific molecular targets and new treatments directed at them.

Targeted drug therapies include:

• Anti-angiogenesis Therapy: This type of treatment focuses on stopping angiogenesis, which is the process of making new blood vessels. Most clear cell kidney cancers have mutations of the VHL gene, which causes the cancer to make too much of a certain protein, known as vascular endothelial growth factor (VEGF). VEGF controls the formation of new blood vessels and can be blocked with certain drugs. Because a tumour needs the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to undernourish the tumour. There are two ways to block VEGF, with small molecule inhibitors of the VEGF receptors (VEGFR) or with antibodies directed against these receptors.

The different drugs used in anti-angiogenesis therapy are:

• Sunitinib (Sutent): This drug acts by blocking both angiogenesis and growth-stimulating proteins in the cancer cell itself. It does so by blocking several tyrosine kinases that are important for cell growth and survival. This drug is taken as a pill daily, typically for four (4) weeks on and two (2) weeks off. Sunitinib may be used in people with advanced kidney cancer, as well as in people with a high risk of relapsing after surgery. This is also known as adjuvant therapy.

• Sorafenib (Nexavar): Similar to sunitinib, the sorafenib drug blocks several tyrosine kinases. Sorafenib attacks both blood vessel growth and other cells that help cancer cells grow. Sorafenib is commonly taken as a pill twice a day.

• Pozapanib (Votrient): Pazopanib is a drug that blocks several tyrosine kinases involved in cancer cell growth and the formation of new blood vessels in the tumour. It is taken as a pill once a day.

• Cabozantinib (Cabometyx): Cabozantinib is a drug that blocks several tyrosine kinases, including some that help form new blood vessels. It may be used as a first treatment for patients with intermediate or poor risked advanced kidney cancer, or in patients with advanced kidney cancer who have tried other targeted drug therapy or immunotherapy. Depending on the type and stage of the cancer, this drug is taken as a pill once a day and has shown results to help patients live longer.

• Lenvatinib (Lenvima): Lenvatinib is a kinase inhibitor drug that helps block tumours from forming new blood vessels and targets the proteins in cancer cells that help them grow. It can also be used with the immunotherapy drug pembrolizumab as a first treatment in people with advanced kidney cancer. Lenvatinib is taken as capsules once a day.

• Bevacizumab (Avastin): Bevacizumab is an IV drug that works by slowing the growth of new blood vessels. It may help patients when used with interferon-alfa immunotherapy.

• Axitinib (Inlyta): Axitinib is a drug that inhibits several tyrosine kinases involved in the formation of new blood vessels. It can be used by itself after at least one other treatment has been tried, or it can be used with certain immunotherapy drugs, like pembrolizumab or avelumab, as the first treatment for people with advanced kidney cancer. Axitinib is taken as a pill twice a day.
• Tivozanib (Fotivda): Tivozanib is a drug that blocks several tyrosine kinases involved in cancer cell growth and the formation of new blood vessels in the tumour. This drug is typically used in patients with advanced kidney cancer after they have tried two or more other systemic drugs, such as chemotherapy, targeted therapy, or immunotherapy. This drug is taken as a pill daily, typically for three (3) weeks on and one (1) week off.

• Belzutifan (Welireg): Belzutifan is commonly used in patients with von Hippel-Lindau (VHL) disease who have kidney cancer and do not require surgery right away. Belzutifan is a type of drug known as a HIF inhibitor. It blocks a protein called hypoxia-inducible factor 2 alpha (HIF-2a), which is involved in both cancer cell growth and the formation of new blood vessels in tumours. This drug is taken as pills, typically once a day.
• mTOR Inhibitors: Mammalian target of rapamycin (mTOR) inhibitors is another form of targeted drug therapy treatment used in kidney cancer. Everolimus (Afinitor) and Temsirolimus (Torisel) are drugs that target a certain protein that helps cancer cells grow, called mTOR. Studies show that these drugs slow cancer growth. Temsirolimus is given as an intravenous (IV) infusion, typically once a week while Everolimus is taken as a pill once a day.

For patients who are too sick for or opt out of surgical treatment, ablation can sometimes be used to potentially destroy the kidney tumour. This approach is usually considered for small kidney cancers (less than four (4) cm across.

• Cryotherapy (Cryoablation): Cryotherapy is used to treat small, early-stage kidney cancers which are less than four (4) centimetres across. In some patients, it can cure the cancer without removing the kidney. Cryotherapy uses extreme cold to destroy the tumour. A hollow probe (needle) is inserted into the tumour either through the skin (percutaneously) or during laparoscopy. Cold gases are passed through the probe, creating an ice ball at its tip that destroys the tumour. To ensure the tumour is destroyed without too much damage to nearby tissues, the doctor carefully watches images of the tumour during the procedure with ultrasound, CT or MRI scans or measures the tissue temperature.
• Radiofrequency Ablation (RFA): Radiofrequency ablation (RFA) is a treatment that uses image guidance (ultrasound or CT scan) to place a needle through the skin into a kidney tumour. In RFA, high-frequency electrical currents are passed through an electrode in the needle, creating a small region of heat. The heat helps destroy the cancer cells.