Clear cell ovarian cancer: what it is, how it is treated and the outlook

Most ovarian cancers are epithelial, meaning they start in the surface layer of the ovary or the nearby fallopian tube. Within that group there are several types that look different under the microscope and behave differently. Ovacome, the UK ovarian cancer support charity, describes clear cell carcinoma as an uncommon type of epithelial ovarian cancer. It makes up about 5 to 10 in every 100 ovarian cancers in the western world, but about 1 in 4 in East Asia.

The Eve Appeal puts the share at around 13% of epithelial ovarian cancers and says that people diagnosed with clear cell cancer are often younger, with an average age at diagnosis of 55 compared with 64 for serous carcinoma. It explains that the name comes from the appearance of the cancer cells, which contain glycogen and look clear under the microscope. Ovacome adds that the cause is likely to be different from the most common type, high grade serous cancer, and that it may develop from other ovarian tumours called adenofibromas.

Ovacome says that a family history of clear cell ovarian cancer may increase the risk, that there is an association with Lynch syndrome, an inherited condition that increases the risk of several cancers, and that it may be more common in people with a history of endometriosis. The Eve Appeal says endometriosis has been associated with 33% to 37% of clear cell ovarian cancers, while stressing that for the majority of people with endometriosis it does not lead to a cancer diagnosis.

The Eve Appeal also notes that, unlike high grade serous and endometrioid cancers, clear cell cancers have no link with family history in its account, and that 85% have wild-type TP53 with fewer BRCA1 and BRCA2 germline changes than high grade serous cancers. The two charities therefore describe the family-history picture slightly differently. If you have a relevant family history, a GP or clinical genetics service can explain what applies to you.

Ovacome says that symptoms of clear cell ovarian cancer are often experienced at an earlier stage than other types. People may notice a lump in the abdomen or pain or discomfort. It also warns of an increased risk of deep vein thrombosis and pulmonary embolism (a blood clot in the lungs), which can be the first sign of the cancer.

In ovarian cancer generally, the CA125 blood test is used as part of diagnosis. Ovacome states that CA125 is not always raised in clear cell cancers, so it may be less reliable in this type. Scans, surgery and examination of the removed tissue by a pathologist therefore play a larger part in reaching and confirming the diagnosis. Any persistent bloating, abdominal pain, feeling full quickly or needing to pass urine more often than usual should be discussed with a GP, as in all suspected ovarian cancer.

According to Ovacome, the first treatment for clear cell carcinoma is the same as for other, more common forms of ovarian cancer: surgery, usually a total abdominal hysterectomy, removal of both ovaries and fallopian tubes and removal of the omentum, a fatty sheet of tissue covering the abdominal organs. Lymph glands in the pelvis and the back of the abdomen may also be removed to show the stage, and fluid from the abdomen is tested for cancer cells. A pathologist examines the tissue.

After surgery chemotherapy with two drugs, carboplatin and paclitaxel, is likely to be offered. Ovacome explains the aim: where all visible cancer has been removed, to reduce the risk of the cancer returning, and where it cannot be completely removed, to lengthen the time until it returns. It also says clear cell tumours respond less fully to chemotherapy, so the benefit may be smaller. The Eve Appeal gives the standard as debulking surgery followed by six cycles of carboplatin and paclitaxel, and notes that response rates in recurrent disease range between 1% and 9%.

For stage 1a cancer, which is within one ovary or fallopian tube and has not spread, Ovacome says fertility-sparing surgery may be possible, removing the affected ovary and tube while leaving the womb and other ovary so that pregnancy may still be possible.

Ovacome reports that a trial of a different treatment to carboplatin and paclitaxel found no advantage, so carboplatin and paclitaxel remain standard. Research suggests chemotherapy might be avoided for cancer confined to the ovary where lymph nodes have been assessed, and that radiotherapy or intraperitoneal chemotherapy may be effective, although the latter is not part of routine practice. Trials of nintedanib, pembrolizumab and an ATR inhibitor were in progress when the page was written.

The Eve Appeal says that PARP inhibitors, used in BRCA-altered cancers, may have limited use here, and that the most frequent changes in clear cell cancers are in the ARID1A gene, which may offer future treatment opportunities. Because clear cell cancer is rare, Ovacome notes that trials are only open in a few centres, but you may be able to be referred to one.

Being diagnosed with a rarer type of ovarian cancer can feel isolating, as there is less published information and fewer people with the same diagnosis. Ovacome offers an online support group for people with rarer types of ovarian cancer, and both Ovacome and the Eve Appeal provide specialist nurse information services. It is reasonable to ask your oncology team to explain how your type differs from the more common types, what the aim of each treatment is and whether a trial is suitable.

Ovarian cancer treatment in the UK is usually delivered through specialist gynaecological oncology teams on the NHS. Private care is available alongside or instead, but because clear cell cancer is rare, the experience of the multidisciplinary team, access to trials and the pathology review all matter, so it is worth asking how a private opinion would connect with your NHS team.