Ovarian cancer – are we any further forward in earlier detection?

This blog is written by our clinicians and aims to keep patients informed with up to date information on medical conditions. The editor of the blog is Dr Cristina Romete.

Ovarian cancer is the 6th most common female cancer in the UK, with around 7,500 new cases diagnosed each year.  This is equivalent no 20 new cases being diagnosed each day (1).

Unfortunately, it is a condition that is often diagnosed late, with only a third of women surviving more than 10 years after their diagnosis. 

It is thought that at least 1 in 10 ovarian cancers are preventable.  There are over 30 different types of ovarian cancers, however these arise from 3 particular cell types present within the ovaries:

Surface Epithelium – cells covering the outer lining of the ovaries

Germ Cells – cells that are destined to form eggs

Stromal Cells – Cells that release hormones and connect the different structures of the ovaries

One of the main reasons for late diagnosis is that the symptoms of ovarian cancer can be vague and difficult to spot.  Tiredness, persistent bloating, early satiety (feeling full soon after starting a meal), increased frequency of urination, and changes in bowel movements are all possible signs of ovarian cancer – but are often attributed to other causes.

Another reason is that at present, there is no national screening programme for ovarian cancer  – as there is no one single test that can reliably help to detect it in its early stage.

What are the current options for detection?

Examination 

It is essential that any woman presenting with symptoms mentioned above undergoes a clinical examination by a health professional.  This will include an abdominal examination to detect any swellings in the lower abdomen, however it will often be necessary for the clinician to also undertake an internal/bimanual examination.  This involves inserting two gloved fingers into the vagina after lubrication and using the other hand to feel outside on the lower abdomen. This allows the womb and ovaries to be palpated in order to check for swellings that may not be found through simple abdominal examination.  If this is not possible, then the clinician will advise an ultrasound as the next step if appropriate (see later).

Blood Tests

CA-125

A blood test called CA-125 is currently available nationwide, and is often carried out in the community if there is any suspicion of ovarian malignancy.  CA-125 is also known as cancer antigen 125. It is considered a tumour marker, as it is a protein that is found on ovarian cancer cells. However, whilst raised levels can indicate a possibility of cancer, CA-125 levels are also raised in several other non-cancerous conditions, for example endometriosis, fibroids, pregnancy, and even during a woman’s period.  It can also be raised in other cancers and is not specific to ovarian. It is often used as a test after there has been a diagnosis of ovarian cancer in order to monitor treatment success and detect recurrence.   

It is also important to note that not all ovarian cancers will produce this protein – and some will not produce the protein until a later stage.  However, a raised CA-125 along with symptoms mentioned earlier, should lead to further investigations.

HE4/CA-125/ROMA

Another option in blood tests is to include a HE4 blood test. This is not currently available on the NHS, but is available in the private sector and in some secondary care (hospital sectors).  This is a new tumour marker for ovarian cancers (although also expressed in others). Evidence has shown that it is consistently over-expressed in epithelial ovarian cancers, with only minimal production by normal ovarian tissue.

Together, the 2 blood tests have shown to have higher sensitivity and specificity for detection of ovarian cancer when compared with CA-125 alone (2).  Furthermore, an algorithm has also been developed alongside the 2 blood tests (Risk of Ovarian Malignancy Algorithm (ROMA)), which classifies patients as being at low or high risk for malignant disease. 

Imaging Options

One of the next investigations for detection of ovarian malignancy is ultrasound of the abdomen and pelvis.  This can be done by the transabdominal route (over the abdomen) or transvaginal route (whereby the probe is inserted into the vagina) so that the womb and ovaries can be assessed for any abnormalities.  Findings suggestive of ovarian malignancy then warrant an urgent referral to a specialist team who will then likely perform further investigations to gauge the extent of the disease, for example CT scans, laparoscopies (keyhole examination of the pelvic organs) and/or biopsies to find out the tissue type of the cancer.

New possibilities in detection

A recent paper published in the British Journal of Cancer has shown the development of a blood test that could potentially detect the presence of ovarian cancer up to 2 years before current tests.  The test looks for 4 particular proteins in the blood, the presence of which indicated increased chance of the epithelial type of ovarian cancer. However the study involved only a small number of samples and further trials are needed (3).

Similarly, a research group in Adelaide found that they could use an altered bacterial toxin from a common bacterium to look for abnormal sugars that are found only on ovarian cancer cells.

The new blood test detected significant levels of the cancer marker in 90 percent of samples from people with early stage ovarian cancer and from all of the samples from people with more advanced ovarian cancer.  The test appears to be specific, as it did not detect the abnormal sugar in any blood samples from healthy participants who served as a control population (4). Again, further trials are required before this becomes available for widespread use.

In conclusion, the possibility of a screening method for earlier detection of ovarian cancer remains out of reach at present.  The best method at present is ensuring that women of all ages are aware of the various symptoms of ovarian cancer and how it presents – and to consult with their GP if they have any concerns regarding persistent abdominal symptoms.

 

References

(1) https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer#heading-Four

(2) J Ovarian Res. 2019; 12: 28. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review.

Vincent Dochez, Hélène Caillon, Edouard Vaucel, Jérôme Dimet, Norbert Winer, and Guillaume Ducarme.

(3) British Journal of Cancer vol 121, pages 483-489 (2019)

volume 121, pages483–489 (2019)Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel. 

Matthew R. Russell, Ciaren Graham, Alfonsina D’Amato, Aleksandra Gentry-Maharaj, Andy Ryan, Jatinderpal K. Kalsi, Anthony D. Whetton, Usha Menon, Ian Jacobs and Robert J. Graham.

(4) Biochemical and Biophysicial Research Communications.Volume 507, Issues 1-4, December 2018, pages 173-177.

Detection of N-glycolylneuraminic acid biomarkers in sera from patients with ovarian cancer using an engineered N-glycolylneuraminic acid-specific lectin.

L.K.ShewellaJ.J.WangaJ.C.PatonbA.W.PatonbC.J.DayaM.P.Jennings.

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