Virtual Medical Centre

Kidney Cancer (Renal Cell Carcinoma; RCC)

• What is Kidney Cancer?
• Who gets Kidney Cancer?
• Predisposing Factors
• Progression
• Probable Outcomes
• Clinical Examination
• How is Kidney Cancer Diagnosed?
• How is Kidney Cancer treated?
• Kidney Cancer References
• Drugs/Products Associated with Kidney Cancer

What is Kidney Cancer?

The kidneys are paired organs in the abdomen of the human body. They filter the blood to remove toxins, waste chemicals and water. This filtered fluid is then concentrated to form urine. From the kidneys, the urine passes out into the ureters (connecting pipes) to be stored in the bladder.

The kidneys also produce a hormone that stimulates the bone marrow to produce red blood cells. Other hormones are produced and act on the kidneys to regulate how much water is kept in the body and how much is passed out as urine.

For more information, see the Renal System.

Renal cell carcinoma (RCC) is the most common form of cancer that originates (starts to grow) in the kidney. Cancers that have started to grow in a particular location (i.e. they have not spread there from somewhere else) are known as primary cancers. Cancers that have spread from somewhere else are known as "secondary cancers" or "metastases". Secondary cancer in the kidney is more common than primary kidney cancer. "Renal" is a technical word referring to the kidney. Carcinomas are cancers that grow from cells that line body organs (epithelial cells).

RCC occurs due to mutations (abnormalities) of cells in the kidney's filtering system. RCCs make up 80-85% of primary kidney (renal) cancer. Other rarer types of kidney cancer include:

• Transitional cell carcinomas, which are the next most common type (8%);
• Collecting duct tumours;
• Renal sarcomas;
• Lymphomas;
• Carcinoids;
• Oncocytomas;
• In children, nephroblastoma (Wilms' tumour) makes up 5-6% of primary renal kidney tumours; and
• Renal medullary carcinoma is a rare complication of sickle cell disease.

Von-Hippel Lindau syndrome is a condition which causes RCC affecting both kidneys and causes tumours in other organs, because of an underlying genetic disorder.

Who gets Kidney Cancer?

Worldwide, over 100,000 people die of RCC each year. Renal cell carcinoma is the seventh most common cancer and tenth most common cause of cancer-related deaths among men. Overall, approximately 2-3% of all cancers are renal cell carcinomas. Renal cell carcinomas make up 80 - 85% of all primary renal cancer in adults.

Males were previously thought to have been twice as likely to develop RCC as females, however this gap is narrowing.

The number of cases of RCC being diagnosed is increasing by approximately 2% per year. This may be because many RCCs are now diagnosed by coincidence when someone has scans (such as ultrasounds or CT scan) performed for other reasons. It is possible that because such scans are becoming more common, more RCC is being diagnosed, and at an earlier stage. The average size of RCCs at diagnosis is decreasing. The number of deaths due to RCC are also decreasing.

In Australia, there are just over 2,000 new cases of primary kidney cancer diagnosed each year. Australians have a 1 in 74 risk of developing RCC during their lifetime. Kidney cancer caused 855 deaths in Australia in 2007 (539 men, 316 women), accounting for 0.6% of all deaths.

Primary kidney cancer is mostly a disease seen in adults over 40. The average age of people found to have renal cell carcinoma is 55 years. The disease is rare in children.

Kidney cancer can be classified into several different types based on the appearance of the cancer cells under a microscope (this is called the microscopic appearance or microscopy), and other genetic factors. The main subtypes are:

• Clear cell carcinoma (75-85%);
• Papillary cell (chromophilic) carcinoma (10-15%);
• Chromophobic carcinoma (5-10%);
• Oncocytic (uncommon); and
• Collecting duct (very rare).

Fewer than 3% of RCCs are unclassified, and these tumours are thought to have a worse prognosis.

Translocation carcinomas are a type of RCC that occur in children who have received chemotherapy for malignancy, bone marrow transplant preparation, or autoimmune disorders.

Knowing the type of renal cancer will help your doctors to make the most appropriate decision about treatment options.

Predisposing Factors

RCC is linked to a number of risk factors. These include:

1. Cigarette smoking, which is the most important risk factor. It doubles the likelihood of developing RCC, and may be associated with up to one third of all cases;
2. Acquired cystic kidney disease: dialysis patients (who require a machine to filter their blood, because their kidneys do not work well enough) who develop polycystic disease of the kidneys appear to be most at risk for RCC. The estimated risk of RCC amongst this group is 30 times greater than the general population. Acquired cystic disease develops in approximately 35 to 50% of chronic dialysis patients. Around 6% of these eventually develop RCC, commonly with multiple tumours in both kidneys. Men (ratio 7:1) and people with large cysts in large kidneys appear to be at significantly increased risk of developing kidney cancer, which tends to occur after 8-10 years of dialysis;
3. Obesity, which is being very overweight, appears to be associated with an increased risk of developing RCC in both men and women;
4. High blood pressure, also known as hypertension, has been found to be a risk factor for RCC, independently to obesity and smoking;
5. Occupational exposures to toxic compounds: risk of RCC is increased in workers exposed to asbestos, cadmium, petroleum products, dry-cleaning solvents, as well as those who work in the iron and steel industries;
6. Genetic predisposition: several genetic syndromes have been associated with an increased risk of RCC. These include von-Hippel Lindau (VHL) syndrome, hereditary papillary renal cancer, hereditary leiomyoma RCC syndrome, and Birt-Hogg-Dube syndrome;
7. Unopposed oestrogen therapy: One study found that women who have more than 5 children are at increased risk of developing RCC. Use of the combined oral contraceptive pill was associated with a slightly reduced risk of RCC;
8. Analgesic abuse nephropathy: individuals who use aspirin or phenacetin contained within analgesics (painkillers) over a long period are at risk of developing chronic renal failure. In addition to kidney failure, they may also be at an increased risk of RCC;
9. Childhood chemotherapy: Chemotherapy given during childhood to treat cancer, autoimmune disorders, or for bone marrow transplantation has been associated with increased risk of RCC (translocation carcinoma as discussed above) because of genetic abnormalities caused by the treatment; and
10. Previous radiation therapy: Renal cell carcinoma caused by radiation occurs in less than 1% of cases of RCC, and in one study it occurred 25-35 years after radiation therapy.

Screening

Due to the fact that RCC is uncommon in the general population, screening of people who have no symptoms of RCC is not recommended. People at high risk for development of RCC may be monitored with abdominal ultrasound, CT, or MRI.

Those who may benefit from screening for RCC include:

• Individuals with inherited conditions such as VHL syndrome or tuberous sclerosis;
• Those with end stage renal disease who have been on long term dialysis;
• Those with a strong family history of RCC; or
• Individuals with a history of previous kidney radiation.

Progression

Renal cell carcinomas often cause few symptoms, and so they may be diagnosed quite late. They also tend to spread to other organs quite early. About one quarter of RCCs will have spread to other organs by the time they are recognised and diagnosed. 40-50% of patients with RCC will eventually develop kidney cancer elsewhere (metastatic disease). RCCs tend to start as small tumours, which get larger, then grow into surrounding tissue, before spreading to nearby organs, then elsewhere.

The common sites for metastasis (spread) of RCC include:

• Local lymph nodes;
• Lungs (>50%);
• Bones (>30%);
• Liver;
• Soft tissue;
• The adrenal gland on the same side as the affected kidney;
• The other kidney; and
• Brain/central nervous system.

Staging

At the time as someone is diagnosed with kidney cancer, the specialist will determine the "stage" of their disease. There are four stages. Depending on the stage of the disease (i.e. how big the tumour is, or whether it has spread), the best decision about treatment and the likely outcomes can be discussed. The stages below are based on the Robson system, which is one of the methods for staging RCC that is used in Australia. The survival rates quoted are general guidelines only, and should be discussed further with your doctor.

• Stage 1: the cancer is only within the kidney, and has not spread. This stage has the best long-term survival and is most likely to be cured with surgery. The five year survival rate is almost 90%.
• Stage 2: the cancer has spread outside of the kidney to the surrounding fat, or to the adrenal gland, which sits on top of the kidney. This stage also has a high rate of survival and surgery is a good treatment option. The five year survival rate is more than 75%.
• Stage 3: the cancer may be of any size, but it extends outside the capsule of the kidney and into blood vessels. In this stage, the specialist will give advice about appropriate treatment. There is a 5 year survival rate of close to 65%.
• Stage 4: the cancer of the kidney may be of any size. However, in this stage the tumour has spread outside the kidney to other organs (in addition to, or other than the adrenal gland on the same side) and so has the lowest rate of long-term survival because. The 5 year survival rate is 10%.

The table below summarises the staging of RCC. The TNM column on the left is one method of staging RCC, while the Robson Stage on the right is another method that is used in Australia. The extent of disease column describes how large the RCC is, and how far it has spread at the time the person is diagnosed.

Staging at presentation

Figure 1: Necrosis haemorrhage and tumour in the kidney.