Clear cell renal cell carcinoma (RCC) gets its name from how it looks under a microscope. The cancer cells look pale or see-through — a little like bubbles. Among adults, clear cell RCC is the most common subtype of renal cell cancer. After a diagnosis, doctors need to figure out how far the cancer has spread and how fast it may grow. They do this by staging (checking how advanced the cancer is) and grading (checking how abnormal the cancer cells look). This helps show whether the cancer is likely to grow and spread fast.

In this article, we’ll explain what staging and grading mean, how doctors use them to understand the risk of cancer getting worse, and how this information helps determine treatment options. Whether you’ve been diagnosed with clear cell RCC or are supporting a loved one with kidney cancer, this guide can help you know what to expect.

What Is Clear Cell Renal Cell Carcinoma?

Clear cell RCC is a type of kidney cancer that starts in the renal cortex — the outer part of the kidney where blood is filtered. It begins in the epithelial cells, which line the tubules (tiny tubes) inside the kidney. Clear cell RCC accounts for about 75 percent to 85 percent of all renal cell carcinomas.

This type of cancer usually forms a single mass (lump). However, sometimes there can be more than one tumor in the same kidney or one in each kidney. Under the microscope, the tumor cells look clear or pale because they store fat and sugar.

Clear cell RCC is different from other subtypes of renal cell carcinoma, like papillary RCC and chromophobe RCC. These subtypes are less common, act differently, and may need different treatments.

How Common Is Clear Cell RCC?

Clear cell RCC mostly affects older adults, with the average age at diagnosis around 64. Clear cell RCC is almost twice as common in males as in females, according to StatPearls, an online source of educational materials for healthcare professionals.

Each year, about 295,000 cases of clear cell RCC are diagnosed worldwide. Incidence — the number of new diagnoses — has been rising, but thanks to newer and more effective treatments, the number of deaths is going down. Clear cell RCC accounts for up to 2.6 percent of all cancer-related deaths.

Risk Factors for Clear Cell RCC

Doctors don’t always know why a person develops clear cell RCC, but certain factors can make it more likely. One of the biggest risk factors is a condition called von Hippel-Lindau disease — a rare genetic condition caused by a change in a cancer-fighting gene. People with this disease may get clear cell RCC at a younger age and have tumors in other parts of the body, such as the adrenal glands.

Other common risk factors for clear cell RCC include:

• Smoking or using tobacco products
• A high body weight
• High blood pressure
• Kidney failure that requires dialysis (a treatment that does the work of the kidneys)
• Family history of kidney cancer
• Long-term use of certain pain medicines, such as acetaminophen and aspirin

Workplace exposure to certain chemicals, such as cadmium or asbestos, may also raise the risk. Having one or more of these factors doesn’t mean someone will definitely get cancer, but knowing about them helps doctors understand who might be more likely to develop clear cell RCC.

How Aggressive Is Clear Cell Renal Cell Carcinoma?

Clear cell RCC can behave in different ways. Some tumors grow slowly and stay in the kidney. Others grow faster or spread to other parts of the body, a process known as metastasis. To figure out how aggressive the cancer is, doctors use two main tools: staging and grading.

Staging of Clear Cell RCC

Cancer staging shows how large the tumor is and whether it has spread. Doctors use a system called TNM, which stands for “tumor, nodes, and metastasis.” Kidney cancer stages range from 1 to 4. A lower number means the cancer has not spread, and a higher number means the cancer is more advanced. Here’s a simple breakdown:

• Stage 1 — The tumor is 7 centimeters (about 2.75 inches) or smaller and only in the kidney.
• Stage 2 — The tumor is larger than 7 centimeters but is still just in the kidney.
• Stage 3 — The tumor has spread to nearby blood vessels or tissues around the kidney. It may also be in nearby lymph nodes but hasn’t reached other organs.
• Stage 4 — The cancer has spread far from the kidney to places like the lungs, liver, bones, or brain. This is called distant metastasis. It may also have grown beyond Gerota’s fascia (the kidney’s outer covering) or into the adrenal gland.

Stage 4 RCC is also called metastatic renal cell carcinoma.

Tumor Grading of Clear Cell RCC

Tumor grading describes how abnormal the cancer cells look and how likely they are to grow or spread. Doctors check this by taking a bit of tumor tissue during a biopsy or surgery and looking at the sample under a microscope.

Low-grade (grade 1) tumors look the most like normal cells, whereas high-grade (grade 4) tumors look the most unusual. Clear cell RCC is graded from 1 to 4:

• Grade 1 — Tumor cells look almost like normal kidney cells. These tumors are less aggressive and tend to grow more slowly.
• Grade 2 — Cells look slightly abnormal and grow a little faster.
• Grade 3 — Cells are more irregular and are more likely to grow and spread.
• Grade 4 — Cells look very abnormal and may be sarcomatoid (spindle-shaped) or rhabdoid (rod-shaped). These are signs of a fast-growing, aggressive tumor.

Staging and grading are not the same — stage tells where the cancer is, and grade tells how it might act. Together, they help your oncology (cancer care) and urology (urinary system and kidney care) teams decide on the best treatment. Options may include surgery like partial nephrectomy (removing part of the kidney) or medicines like immunotherapy.

How Does Clear Cell Renal Cell Carcinoma Progress?

Clear cell RCC often starts as a single tumor in one kidney. In the early stages, the primary tumor (original tumor) may grow slowly and stay in the kidney. Sometimes, however, the cancer progresses, which means it becomes more aggressive and spreads. The cancer might grow larger, move into nearby areas, or spread to other parts of the body. Getting the right treatment early can help prevent the risk of progression.

Doctors check for signs of progression using imaging tests like CT scans, blood tests, and regular follow-up visits. Tumors that are bigger, are high-grade, or show signs of necrosis (dead tissue inside) may be more likely to progress or lead to a worse outcome.

Your oncologist (cancer doctor) will explain your cancer’s stage, grade, and risk of progression. They’ll also talk with you about what it means for your care and treatment options. You don’t have to make these decisions alone — your healthcare team will help guide you. You can also turn to your support system, like family, friends, and cancer support groups, for extra help along the way.

Talk With Others Who Understand

On MyKidneyCancerTeam, the social network for people with kidney cancer and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with kidney cancer.

Have you been diagnosed with clear cell renal cell carcinoma? What tests led to your diagnosis? Share your story in the comments below, or start a conversation by posting on your Activities page.