Metastatic Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for 90% of all kidney cancers. RCC usually begins as a tumor growing in one kidney, but it can also arise in both kidneys.

If a tumor in the kidney is left untreated, it is more likely to spread to other parts of the body. This cancer spread is referred to as metastasis and at this stage, the cancer is referred to as metastatic RCC.

Metastatic RCC is also referred to as stage IV RCC, the most advanced stage of cancer. A cancer is described as Stage IV when it has invaded the lymph system or other organs such as the lungs, brain, bones or liver. Since the adrenal gland is connected to the kidney, the cancer cells often travel there first.

In RCC, the risk of metastasis is significant as most cases are not identified during the early stages of the disease, when the tumor is still small and confined to the kidney. Clinical symptoms are generally mild and nonspecific until the cancer progresses to a more advanced stage. Around 20% to 25% of diagnosed individuals have already reached the metastatic phase of the disease.

How cancer spreads

There are three ways in which cancer spreads, namely through tissue, through the lymph system and through the blood.

• Tissue: The cancer invades nearby areas of tissue that surround the area where it originally grew
• Lymph system: The cancer gets into the lymph system, travels along lymph vessels and forms a metastatic tumor in another part of the body
• Blood: The cancer gets into the blood vessels and travels to another part of the body where it forms a metastatic tumor.

The metastatic tumor that forms is comprised of the same type of cancer cells as the original or “primary” tumor. If RCC spreads to the bone, for example, the cancer cells in the tumor that forms there are cancerous renal cells and the cancer is still called metastatic renal cell cancer rather than bone cancer.

Prognosis

After RCC has spread to other organ systems in the body, a patient’s 5-year survival estimate plummets to 5-15%. A majority of long-term survivors with stage IV RCC (i.e. those that survive more than five years) are patients with solitary metastases that were surgically resected.

Generally, metastatic renal cell carcinoma cannot be cured, albeit the chances of survival may improve if any detectable cancer is removed from the kidney and other affected organs

Treatment

Surgery is often not an option and treatment is focused on slowing disease progression and alleviating symptoms. Surgical removal of the cancer may be possible in cases where the tumor and metastasis can be isolated. Surgery may be performed to remove as much of the tumor as possible (partial nephrectomy) or the whole kidney may be removed (partial nephrectomy). Alternatively, a radical nephrectomy may be performed, where the entire kidney, attached adrenal gland, nearby lymph nodes and other surrounding tissue is removed.

A person with stage IV RCC will be assessed by their doctor to determine their eligibility for surgery. If surgery is not an option, alternative approaches may be used and these are described below:

Biological therapy (immunotherapy)

This involves the use of drugs that manipulate the immune system to target cancer cells. Examples of these drugs include interferon and aldesleukin.

Targeted therapy

These treatments specifically block the abnormal signals in kidney tumor cells, which allow the cells to proliferate. The drugs axitinib, sunitinib and bevacizumab, for example, block the signals that enable the growth of blood vessels that supply the tumor cells with nutrients, enabling their spread. The drugs everolimus and temsirolimus block the signals that enable the growth and survival of tumor cells.

Embolization

Here, a substance is used to occlude blood vessels so that blood flow to cancer cells is blocked. The main disadvantage of this approach is that the substance used may also block blood flow to healthy cells.

Radiotherapy

High-energy radiation is used to target cancer cells, although this tends to be unsuccessful when the cancer has spread to many parts of the body. On the other hand, palliative radiotherapy has an important role in supportive care for metastatic disease.