Uterine clear cell cancer is a rare and aggressive type of endometrial cancer with a generally unfavorable outlook. Treatment involves a combination of surgery, chemotherapy, and radiation therapy.

Uterine cancers start in the uterus (womb). Most diagnoses of uterine cancer affect the endometrium, which is the inner lining of the uterus.

The most common type of endometrial cancer is called adenocarcinoma. However, there are rarer types of endometrial cancer as well. One of these is clear cell cancer.

This article provides details on clear cell cancer, including its symptoms, diagnosis, treatment, and more.

Clear cell uterine cancer is a rare type of endometrial cancer. It’s typically referred to as uterine clear cell carcinoma (CCC) and is estimated to make up fewer than 5% of uterine carcinomas.

Endometrial cancers are divided into two types:

  • Type 1 endometrial cancers are not typically aggressive and are linked to an increased exposure to estrogen.
  • Type 2 endometrial cancers are less common than type 1 endometrial cancers and are not associated with estrogen levels. However, these cancers are much more aggressive.

CCC is a type 2 endometrial cancer. This means it’s more likely to grow and spread quickly and has a less favorable outlook.

As with other types of uterine cancer, the most common symptom of uterine CCC is abnormal vaginal bleeding or discharge. This typically occurs after menopause but can also include bleeding between periods or irregular periods.

Other potential symptoms of uterine cancer in general include:

Uterine cancers such as CCC happen when cells in the uterus start to grow and divide out of control. This results from genetic changes that affect cell growth and division.

Genetic changes can be either inherited or acquired. Therefore, you may be at an increased risk of uterine cancer if it runs in your family. Certain genetic syndromes, such as Lynch syndrome, can also increase your risk of uterine cancer.

Known risk factors for uterine cancer include:

A 2020 study also found that, in comparison to members of other racial groups, Black people were about twice as likely to receive a diagnosis of uterine CCC. While genetics may play a role, disparities in healthcare access and socioeconomic status may also be involved.

If a doctor suspects that you have uterine cancer, they’ll order a transvaginal ultrasound. This helps them visualize your uterus and the surrounding tissues, such as your fallopian tubes, ovaries, and bladder.

Analysis of an endometrial tissue sample is necessary to confirm a diagnosis of uterine CCC. Healthcare professionals usually collect this sample using one of the following methods:

If these methods detect cancer, further tests can help characterize it. To help determine how far the cancer has spread, your doctor may order imaging tests such as:

Because uterine CCC is a more aggressive cancer type, it’s more likely to have spread beyond the uterus at the time of diagnosis.

One of the main treatment options for CCC is surgery. Because CCC is much more aggressive than other endometrial cancers, surgery may be more extensive and involve the removal of your:

After surgery, you’ll likely have chemotherapy, radiation therapy, or both. These treatments can kill any remaining cancer cells and help prevent the cancer from coming back.

Sometimes, doctors do not perform surgery for CCC. This can happen if the cancer has spread to more distant tissues (metastasized) or if you choose not to have surgery. In these situations, you may receive chemotherapy, radiation therapy, or both.

Immunotherapies with chemotherapy

In a 2023 study, researchers found that adding the immunotherapy drug pembrolizumab (Keytruda) to chemotherapy improved overall survival. And another 2023 study found that the immune therapy drug dostarlimab (Jemperli) showed similar positive results when added to chemotherapy treatment.

Targeted therapies

Targeted therapies may be used for high risk or advanced uterine cancer. For example, a 2018 study found that people with HER2-positive clear cell uterine cancer may benefit from targeted drugs such as trastuzumab (Herceptin).

Uterine CCC is more aggressive than other more common types of endometrial cancer. Therefore, it’s associated with a less favorable outcome.

Research has found that the following factors are associated with worse outcomes for uterine CCC:

  • older age at diagnosis
  • deep invasion into the muscle layer of the uterus
  • more advanced stage at diagnosis, which can include spread to:
    • surrounding blood and lymphatic vessels

One 2017 study of 165 people with uterine CCC found that the 5-year overall survival rate was 58%. Two 2021 studies found that the median overall survival times after diagnosis for the groups studied were 40 months and 56 months.

Uterine CCC can also come back after treatment. This is called recurrence. In a 2023 study of 156 people with CCC, 39 people (25%) experienced a recurrence.

Uterine CCC is a rare type of cancer that can affect the endometrium, the inner lining of the uterus. It’s more aggressive than more common types of endometrial cancer, growing and spreading more quickly.

Many times, uterine CCC is diagnosed when it has already spread outside of the uterus. Treatment typically involves some combination of surgery, chemotherapy, and radiation therapy.

The outlook for uterine CCC is generally unfavorable. However, this can depend on many factors, such as the cancer stage, the cancer’s response to treatment, and your age and overall health. Be sure to ask your oncology team about your individual outlook.