Kidney Cancer

What is Kidney Cancer?

Kidney cancer, also known as renal cancer, is a type of cancer that begins in the kidneys. It usually affects only one kidney, but in rare instances the cancer may develop in both kidneys. The kidneys are two fist-sized, bean-shaped organs that lie behind the abdominal organs, with one kidney on each side of the spine. The kidneys are connected to the bladder via two tubes known as the ureters. The main roles of the kidneys are to^1,2:

• Remove excess water, salt, and waste products from the blood in the form of urine.
• Produce a hormone called renin that helps regulate blood pressure.
• Produce a hormone called erythropoietin that signals the bone marrow to make more red blood cells.
• Produce a hormone called calcitriol (a form of vitamin D) that helps the intestine absorb calcium.

Types of Kidney Cancers

Kidney cancer can be grouped according to the type of cell that the cancer originated from³:

• Renal cell carcinoma (RCC): The most common form of kidney cancer in adults is renal cell carcinoma, which begins in the cells that line the kidney’s tubules (tiny tubes that filter the blood). RCC accounts for 85% of all kidney cancers. There are multiple subtypes of RCC, the most common being clear cell renal cell carcinoma which makes up about 80% of all renal cell carcinoma cases⁴.

• Transitional cell carcinoma (TCC): Transitional cell carcinoma (also known as urothelial carcinoma) usually arise from the cells lining the renal pelvis, which is the area where the kidney connects to the ureter. TCC accounts for around 7% of all kidney cancers and can also occur in the ureters or bladder. It is usually treated like bladder cancer.

• Wilms tumour: Wilms tumour, or nephroblastoma, is the most common type of kidney cancer in children but is rare in adults. It accounts for about 5% of kidney cancers.

• Renal sarcoma: This is a rare form of kidney cancer, making up about 1% of kidney cancer cases. It starts in the connective tissues of the kidney.

How Common is Kidney Cancer?

In Singapore, kidney cancer is the seventh most common cancer diagnosed and eighth most common cause of cancer deaths in males⁵. It is less common in females. The incidence (number of cases) of kidney cancer has been steadily increasing over the past 50 years. This is thought to be related to rising affluence and industrialisation leading to increased smoking, occupational exposure to chemical carcinogens (cancer-causing substances), hypertension (high blood pressure) and obesity, which are risk factors for developing kidney cancer (See Kidney Cancer Risk Factors)⁶.

In addition, more frequent use of imaging techniques such as ultrasound and computerised tomography (CT) scans have contributed to the rising number of kidney cancer diagnoses. These imaging scans, done for other health complaints, may lead to the incidental discovery of kidney cancers that are asymptomatic (have not shown symptoms)⁷.

The good news is that most kidney cancers are found at an early stage, before they have spread to distant organs. Treatment for early cancers is more likely to lead to a cure.

What causes Kidney Cancer?

Kidney cancer happens when cells in the kidney develop changes (mutations) in their DNA that cause the kidney cells to grow abnormally and develop into a tumour. The exact trigger for the mutations is not fully known.

Kidney Cancer Risk Factors

Doctors may not always have an explanation as to why one person develops kidney cancer, and another does not. However, there are certain risk factors that increase the likelihood of a person developing kidney cancer, including^3,8,9:

• Older age: Kidney cancer is rare in people under the age of 50. Around two thirds of kidney cancer cases are diagnosed in those over the age of 65⁷.

• Gender: Kidney cancer is twice as common in men than in women¹⁰.

• Smoking: Smoking is thought to be the cause of more than 30% of kidney cancers¹¹. The risk of developing kidney cancer increases with the duration and number of cigarettes smoked. But the risk falls if you stop smoking, and reduces to nearly the same as for non-smokers after ten years of quitting⁹.

• Obesity: Being overweight or very overweight (obese) increases the risk of getting kidney cancer compared to those who are within a healthy weight range. The more excess weight someone carries, the greater the risk. Around 25% of kidney cancers are related to obesity and is thought to be due to changes in hormone balance in the body that occurs with obesity⁹.

• High blood pressure (hypertension): High blood pressure increases the risk of kidney cancer. The higher the blood pressure, the greater the risk.

• Diabetes: Diabetes can cause long-term kidney damage and kidney cancer. The risk may be higher in people who use insulin to control their diabetes compared to those who use oral medications⁹.

• Advanced kidney disease requiring dialysis: People with kidney failure who receive long-term dialysis (the process of filtering your blood using a machine) have a higher chance of developing kidney cancer.

• Prolonged intake of mild painkillers: Taking pain killers such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) for an extended period of time is linked to a higher likelihood of getting kidney cancer⁷.

• Workplace exposure: Workplace exposure or contact with certain substances such as textile dye, asbestos, arsenic or cadmium over a prolonged period may increase the risk of developing kidney cancer.

• Family history of kidney cancer: Having a first-degree relative (parent or sibling) who had kidney cancer increases your risk of getting it too. This may be due to shared genes, something in the shared environment, or both¹⁰.

• Certain inherited conditions: Some people inherit gene mutations (changes) that increase the risk of kidney cancer and other cancers, such as von Hippel-Lindau disease, Birt-Hogg-Dube syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma or familial renal cancer. However, these inherited syndromes account for only a small percentage of kidney cancers. People with these genetic conditions who develop kidney cancer can have multiple tumours in both kidneys that occur at a younger age than people with non-inherited cancer.

Having one or more of these risk factors does not automatically mean that you will get kidney cancer. Many people with risk factors never develop kidney cancer, whilst some with no known risk factors do.

What are the Signs and Symptoms of Kidney Cancer?

Kidney cancer usually does not show symptoms in its early stages. When they do occur, signs and symptoms of kidney cancer include^8,12:

• Blood in your urine (may appear pink, red, or brown)
• Pain in your side or lower back
• Lump on one side of your abdomen (belly)
• Loss of appetite
• Unexplained weight loss
• Tiredness that is not relieved with rest
• Persisting fever that is not caused by an infection
• High blood pressure
• Anaemia (low red blood cell count)

Many of these symptoms are more likely to be caused by non-cancer ailments such as a bladder or urinary tract infection or a kidney stone. However, if you have any of these symptoms, you should see a doctor to have it checked out and treated if needed.

Diagnosis of Kidney Cancer

If you have symptoms or signs that suggest kidney cancer, your doctor will investigate further to determine if you have cancer. Kidney cancer may be detected through the following procedures and tests^3,13,14:

• Clinical history and examination: Your doctor will ask about your personal and family medical history and perform a physical examination for masses in your abdomen (belly).

• Urinalysis: A sample of your urine is tested to check for infection, blood and protein. Urine cytology, which is a test to look for cancer cells in the urine may also be done.

• Blood tests: Blood tests including urea, electrolytes and creatinine levels (to check your kidney function) and complete blood count (to check your blood cell levels) will be done.

• Abdominal Ultrasound: Ultrasound is an imaging test that uses sound waves to create images of the kidneys and abdomen. It is useful in helping to determine if a mass in the kidneys is a fluid-filled cyst or a solid tumour.

• Computed tomography (CT) or magnetic resonance imaging (MRI): A CT or MRI scan of the abdomen is done to visualise the three-dimensional picture of the kidney and surrounding organs. It can show the size and position of a tumour, blood vessels and whether the cancer has spread elsewhere.

• Kidney biopsy: Biopsies (removal of a small sample of cancer tissue) are not often carried out for kidney cancer as imaging scans (CT or MRI) are usually good at determining if a kidney mass is cancer. If there is uncertainty on the scans, your doctor may recommend a biopsy. The biopsy sample is analysed in a laboratory to determine whether cancer cells are present, and if so, what type of kidney cancer and grade it is (described further below). Genetic testing may also be done on the cancer cells to look for specific protein or gene changes which can influence treatment choice.

How is Kidney Cancer Assessed?

After kidney cancer has been diagnosed, your doctor will determine the extent (stage) of the disease. Staging, usually done with CT scans, PET-CT scans or MRI, is done to find out whether the cancer has spread, and if so, to what parts of the body. Kidney cancer spreads most often to the lungs, bones, lymph nodes, liver and brain.

The stages of kidney cancer are described as^3,15:

• Stage I: The cancer is 7cm or smaller and confined to the kidney.
• Stage II: The cancer is larger than 7cm but still completely inside the kidney.
• Stage III: The cancer has grown into the tissue surrounding the kidney or to nearby lymph nodes, or spread to main blood vessels (renal vein and inferior vena cava). Stage III is also known as locally advanced kidney cancer.
• Stage IV: The cancer has spread beyond the kidney to the adrenal gland (a small gland that sits on top of the kidney), or to distant lymph nodes or other organs such as the lungs, bones and liver. Stage IV is also known as advanced or metastatic kidney cancer.

Kidney cancer is also categorised according to grade. The grade of a kidney cancer is based on how abnormal the cancer cells look under the microscope (ranging from Grade 1 with cells that look like normal kidney cells, to Grade 4 with very abnormal-looking cancer cells) and how likely it is to spread. High-grade cancers tend to grow and spread more rapidly than low-grade cancers and therefore generally have a poorer prognosis (outcome)¹³.

The lower the stage and grade at diagnosis, the higher the chance of successful treatment and long-term survival.

Kidney Cancer Treatment Options

When considering your treatment plan your doctor will take into account the following factors^8,16:

• The stage (extent) of the cancer (size of the tumour and whether the cancer has spread).
• The location of the tumour in the kidney.
• Characteristics of the tumour (which type and grade the cancer is).
• Your age, overall health and any other treatments you may have for other illnesses.
• Your preferences.

The first goal of kidney cancer treatment is to get rid of the cancer. When that is unachievable, the focus may be on stabilising the cancer to prevent its progression and maintaining quality of life for as long as possible. Treatment options for kidney cancer include^4,7,8,17:

• Active Surveillance: In some cases, because kidney cancer may take many years to progress, and treatment does have its risks, doctors may choose to simply monitor the tumour rather than treat it immediately. This is known as “active surveillance”. It may be an option for small cancers less than 3 cm in size or in frail, elderly patients with multiple other medical problems who are not fit for surgery⁷. In active surveillance, follow-up blood tests and scans may be performed at regular intervals to monitor your cancer closely. Treatment may be started if the tests show that your cancer is progressing.

• Surgery: Surgery is the main treatment for most kidney cancers. For early-stage cancers, it may be the only treatment required. If the cancer is high grade (looks very abnormal under the microscope) or has spread beyond the kidney, further treatment(s) after surgery will be required to lower the risk of the cancer coming back. Surgery may be performed either through open surgery or endoscopic (keyhole) surgery (laparoscopic or robotic-assisted laparoscopic surgery). Surgical options include:

  • Radical nephrectomy: This involves the removal of the kidney, adrenal gland and surrounding tissues. When one kidney is surgically removed, the remaining healthy kidney is usually able to maintain the work of both kidneys.

  • Partial nephrectomy (also called kidney-sparing surgery): This involves the removal of the cancer and a small margin of surrounding healthy tissue rather than the entire kidney. It is a common treatment for small tumours that are less than 4cm and may also be considered for patients with cancer in both kidneys and those who have only one healthy kidney. Compared to complete removal of the kidney, partial nephrectomy preserves kidney function and reduces the risk of later complications, such as chronic kidney disease and the need for dialysis, as well as heart and blood vessel disease.

  • Removal of metastasis: If the cancer has spread to a limited number of sites, surgery to remove these tumours may still be useful. This may help subsequent treatments work more effectively.

  • Palliative surgery: If the cancer has spread and cannot be removed, palliative surgery may be performed to relieve symptoms, reduce complications and improve quality of life.

• Thermal ablation: These procedures may be used in certain situations such as for people with small, early-stage cancers or those who have other health problems that make them unfit for surgery. Cryoablation (or cryotherapy) involves freezing the affected kidney area with very cold gas and thawing, in repeated cycles to kill the cancer cells. Radiofrequency ablation uses electrical current to destroy cancer cells by heating them to a very high temperature.

• Arterial embolisation: This procedure involves inserting material into the renal artery (the main blood supply to the kidney) to block blood flow to the tumour. This helps to slow down the growth of the cancer and improve symptoms such as pain or bleeding from the kidney.

• Radiation therapy (or radiotherapy): Radiation therapy is the use of powerful, high-energy beams to kill cancer cells or keep them from growing. It is not used very often to treat kidney cancer. It is sometimes used to treat early-stage kidney cancer in someone who is not healthy enough for surgery or who has only one kidney. Radiation therapy may also be used to relieve symptoms caused by the spread of the cancer to other areas of the body, such as the bones and brain.

• Targeted therapy: Targeted therapies are drugs that block the growth of cancer by interfering with specific molecules present in cancer cells that are involved in tumour expansion and spread. Targeted drug therapy may be used in advanced kidney cancer when surgery is not possible or following surgery to reduce the chance of the cancer coming back. Most of the targeted drugs used to treat kidney cancer work by blocking proteins called tyrosine kinases that normally help cancer cells grow or help them create new blood vessels. These drugs are known as tyrosine kinase inhibitors.

• Immunotherapy: Immunotherapy uses the body's natural defences to fight cancer by enhancing the immune system's ability to attack cancer cells. In recent years, immunotherapy drugs such as PD-1 and PD-L1 inhibitors that target a protein on T cells to boost the immune system have been developed to treat high grade stage I, II and III cancers after surgery to reduce the risk of the cancer returning, and as first treatment for advanced (stage IV) cancers. Immunotherapy drugs may be used in combination with targeted drugs.

• Chemotherapy: Chemotherapy is not a main form of treatment for kidney cancer. It may occasionally be used if other treatment options have failed.

Kidney Cancer Survival Rate

The overall 5-year relative survival rate for kidney cancers in Singapore is around 70%⁶. However, the earlier the cancer is detected and treated, the higher the likelihood for cure. The good news is that close to 50% of kidney cancers are diagnosed in Stage I, which has around 90% 5-year relative survival rate¹⁸.

About 25% of patients are diagnosed with advanced (Stage IV) kidney cancer and the prognosis for this group is significantly less favourable, with a survival rate of 13%¹⁸. It is worth noting however, that survival rate statistics are measured every 5 years and therefore may not reflect the recent advances in kidney cancer treatment. People who are diagnosed with advanced kidney cancer now are likely to have a better prognosis (outcome) than these numbers show.

It is also important to understand that these statistical numbers are obtained from a group of people with the same diagnosis to represent an average. Individuals may differ in their own experience. It is best to discuss your prognosis (outcome) with your treating doctor who would be able to provide you with more specific information based on your personal circumstances.

Kidney Cancer Screening

Screening refers to looking for cancer before a person has any symptoms. There is currently no recommended routine screening for kidney cancer for the general population. A urinalysis (urine test) which is often done as part of a general medical check-up, may sometimes detect small amounts of blood in some people with early kidney cancer. However, kidney cancer may not cause blood in the urine until the cancer is quite large or already advanced and blood in the urine can also be due to other causes such as a urinary tract or bladder infection, bladder cancer and kidney stones¹⁹. If you have one or more risk factors (see Kidney Cancer Risk Factors), it is important to be vigilant and see your doctor for prompt investigation if you have any symptoms.

People at high risk of getting kidney cancer, in particular those with certain inherited conditions or chronic kidney disease treated with long-term dialysis should be closely monitored, usually with regular physical examinations, urinalysis and imaging scans. This may detect kidney cancer at an early stage when the cancer is localised and more likely to be cured with surgery.

Kidney Cancer Prevention

While there is no guaranteed way to prevent kidney cancer, there are some measures you can take to reduce your risk^4,8:

• Avoid or quit smoking: Smoking increases your risk of kidney cancer and many other types of cancers. Quitting smoking can be hard, so ask your health care provider for help. These might include support groups, medicines and nicotine replacement therapy.

• Maintain a healthy body weight: A healthy diet and regular exercise can help you to keep to a healthy body weight and reduce your risk for many conditions including kidney cancer. If you are overweight or obese, talk to your doctor about strategies to help you lose weight in a safe manner.

• Control high blood pressure: If you have high blood pressure, lifestyle measures such as physical exercise, weight loss and dietary changes may help to reduce your blood pressure. Medications may be needed if your blood pressure is very high or does not respond to lifestyle changes. Discuss your treatment options with your doctor.

• Control diabetes: If you have diabetes, ensure that your blood sugar levels are controlled and see your doctor regularly for optimal management.

• Limit use of painkillers: Avoid long-term use of painkillers such as paracetamol and non-steroidal anti-inflammatory drugs as much as possible. If you have ongoing pain, you should see your doctor to have it further investigated and treated.

• Avoid workplace exposure: Take precautions and follow all safety guidelines carefully if you work with potential carcinogens such as textile dye, asbestos, arsenic or cadmium.

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