Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma, or ccRCC, is the most common of the three subtypes of kidney cancer. It makes up about 80% of all cases and gets its name from the appearance of the cancer cells, which look clear like glass under a microscope.

The second most common type of kidney cancer is papillary renal cell carcinoma, which accounts for 15% to 20% of cases. The rarest type is chromophobe renal cell carcinoma with about 5% of all diagnosed cases.

The kidneys are bean-shaped organs located on either side of the spine, behind the stomach. Each kidney is about 5 inches long. A kidney's main job is filtering the blood. About 76,000 cases of kidney cancer are reported each year, according to the American Cancer Society.

This article discusses the symptoms and causes of clear cell renal cell carcinoma. It also addresses the diagnosis and treatment of the disease.

Clear Cell Renal Carcinoma Symptoms

Patients with ccRCC may feel tired or notice a loss of appetite. Sometimes, patients do not have any noticeable symptoms. The most common symptoms are:  

• Blood in the urine
• Feeling tired
• Fever unrelated to a cold or flu
• Loss of appetite
• Lump on the side
• Pain in the back or side that doesn't go away
• Unexplained weight loss

What Causes Clear Cell Renal Carcinoma?

Several factors can cause someone to develop ccRCC, including genetics, age, and lifestyle factors. Known causes include:

• Older age: The risk of developing kidney cancer increases with age. The average age of people diagnosed with kidney cancer is 64 years old. Kidney cancer is uncommon in those under age 45.
• Gender: Men develop kidney cancer more often than women. In 2021, the American Cancer Society estimated 48,780 cases in men versus 27,300 in women.
• Weight: Being obese can cause changes in certain hormones, increasing the risk of developing kidney cancer.
• High blood pressure: Those living with high blood pressure are at higher risk.
• Kidney dialysis: Those who are on dialysis to filter and purify the blood through a machine are also at greater risk of developing kidney cancer. Experts believe that this is due to the presence of kidney disease rather than the impact of dialysis.
• Tobacco use: Smoking cigarettes, pipes, and cigars is associated with an increased risk of developing kidney cancer, and cancer in general.
• Occupational exposure: Exposure to asbestos exposure or trichloroethylene may lead to a higher risk of kidney cancer.

How Is Clear Cell Renal Carcinoma Diagnosed?

The rate of new kidney cancers rose during the 1990s but has leveled off in more recent years. Part of the increase in diagnosed patients was attributed to the use of newer imaging tests such as CT scans that identify tumors before they progress.

Clear cell renal cell carcinoma tends to be identified at a later stage. For people who don't have symptoms, these tumors can be discovered if the person has an imaging test for another reason. Imaging and biopsies are the two most common ways of diagnosing this type of cancer.  

Tests include:

• Blood and urine tests: While they cannot determine a completely accurate diagnosis, blood and urine tests can detect the number of red blood cells in the blood, which may indicate that kidney cancer has occurred.
  
• Imaging: To check for ccRCC, doctors commonly order imaging scans such as X-ray, computerized tomography (CT) scan, or magnetic resonance imaging (MRI) to detect tumor growth. 
  
• Biopsy: During a biopsy procedure, your doctor will take a small sample from the tumor with a needle. An expert, called a pathologist, will study cells from the sample under the microscope to determine the type of tumor.

Treatment for Clear Cell Renal Carcinoma

There are several options for treating ccRCC. Depending on the size of the tumor and how far it has spread, different treatment options may be combined or sequenced, one after another. The main treatment options include:

• Cryotherapy (cryoablation): When surgery may not be an option, doctors may recommend “freezing” the cancer to destroy the tumors. A narrow needle is placed into the tumor passing very cold gases into the tumor cells. This destroys the tumor cells without causing too much damage to nearby tissue.
  
• Immunotherapy: These medications are approved to help the body’s immune system fight or slow the spread of tumors. Some examples include Opdivo (nivolumab), Yervoy (ipilimumab), and Keytruda (pembrolizumab).
  
• Radiation therapy: Following surgery or other treatments, doctors may recommend radiation therapy (high-energy rays) to shrink or defeat tumor cells.
  
• Radiofrequency ablation: A needle with a high-frequency electrical current is inserted into the tumor. The difference between radiofrequency ablation and cryoablation is that the needle is heated up to damage the kidney cancer cells.  
  
• Surgery: Surgeons remove as much of the cancer growth as possible from one or both kidneys.
• Targeted therapy: These medicines work differently from standard chemotherapy by targeting specific changes or mutations in the kidney cells and reducing damage to healthy cells. Some examples include Inlyta (axitinib), Cometriq (cabozantinib), Votrient (pazopanib), Nexavar (sorafenib), and Sutent (sunitinib).
• Vascular endothelial growth factor (VEGF) inhibitors: These cancer drugs, such as Avastin (bevacizumab), helps prevent the growth of new blood vessels, including ones that feed the tumor cells.

What Is the Survival Rate for Clear Cell Renal Cell Carcinoma?

The prognosis for people with ccRCC has improved over time with the introduction of newer medicines and advanced surgical methods. The five-year survival rate for people with ccRCC is 50%–69% (the percentage of people who are still alive five years after diagnosis). The long-term prognosis is affected by several factors, including:

• Age: Advanced age is associated with more aggressive forms of kidney cancer and lower survival rates.
• Size of tumor: One study found that survival rates were higher in people with tumors less than 4 centimeters and lower in those with tumors that were 7 centimeters. When the tumor is larger or has spread to other parts of the body, treatment is more difficult, and the five-year survival rate drops to about 10%.
• Timing of diagnosis: People diagnosed early in their disease have an even greater five-year survival rate of 70%–94%.

Summary

Clear cell renal cell carcinoma, or ccRCC, is the most common form of kidney cancer. Symptoms of kidney cancer may not be noticeable until it is more advanced. There are several treatment options to remove or destroy cancer cells in the kidney. Within the past few years, new immunotherapy drugs have harnessed the power of the immune system to fight kidney cancer and provide hope to diagnosed patients.