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Screening

Why screening for ovarian cancer may be important

Early stage ovarian cancer confined to the ovaries (stage I) has an extremely good outlook and can often be successfully treated. Unfortunately most ovarian cancers are not recognised at an early stage for a number of reasons.

First, cancer of the ovary usually develops after the menopause when the ovaries are inactive and abnormal function of the ovary is not therefore readily noticed.

Second, the ovaries are located deep inside the pelvis and are inaccessible to examination.

Finally, even when symptoms do occur they are usually vague, non-specific symptoms which could be due to a host of other causes. For these reasons by the time most women with ovarian cancer develop significant symptoms and their cancer is diagnosed it has spread outside the ovaries to the pelvis (stage II), the abdomen (stage lll) or more distant sites (stage IV) and is far more difficult to treat successfully. This information suggests that an effective method of screening to detect early stage ovarian cancer may save the lives of many women who develop the cancer.

What screening tests are available?

Three potential methods of screening for ovarian cancer have been assessed:

1. Internal examination can be performed to identify enlarged ovaries. Although internal examination can detect large ovarian tumours even experienced doctors are not able to reliably detect ovarian cancer at an early stage. Internal examination is not regarded as an effective method for early detection of ovarian cancer.

2. CA 125 is a protein released into the circulation in high levels in most women with ovarian cancer. The CA 125 blood test is frequently used to diagnose ovarian cancer in women who have symptoms and to monitor women after and during treatment of ovarian cancer. It is important to recognise that CA 125 is also produced by many normal tissues and levels in the bloodstream can therefore also be raised in normal situations (e.g. pregnancy, menstruation) and benign conditions as well as ovarian cancer. The CA 125 test is easily and quickly performed on a small blood sample sent to the laboratory.

3. Ultrasound scanning is the same technique as is used in pregnancy and can be used to visualise the size and texture of the ovaries. In ovarian cancer the ovaries increase in size and the texture becomes abnormal due to formation of cysts and solid growths. Unfortunately some of these abnormal features also occur in benign ovarian tumours and other conditions in the pelvis. So, as with CA 125, it is important to realise that ultrasound results can be abnormal even when there is no cancer present. Ultrasound scans can be performed either by placing a probe on the abdomen or by inserting a probe into the vagina.

How effective are the screening tests?

There is no doubt that screening can detect ovarian cancer early. A number of large-scale studies have been performed to look at the possibility of using either CA 125 or ultrasound to screen for ovarian cancer. Two of the largest studies of screening for ovarian cancer have been performed in the UK.

The King's College Study investigated the role of ultrasound in over 5,000 women and demonstrated that ultrasound can detect ovarian cancer at an early stage. The Royal London/St Bartholomew's Hospital Study assessed the use of CA 125 in combination with ultrasound in 22,000 women. This study revealed that it was possible to detect ovarian cancer before any symptoms developed. However, both these studies were small and could not provide information on whether detecting the ovarian cancer by screening saved the lives of the women.

It is still uncertain whether screening actually saves lives from ovarian cancer. Although screening with CA 125 and/or ultrasound can detect ovarian cancer early, it is important to be aware that this does not necessarily mean that screening will save lives. It is possible that even though screening detects cancer early it is not early enough to make a difference. Screening will only be worthwhile if it detects ovarian cancer sufficiently early to make treatment more effective. Large studies are in progress at present to determine whether screening saves lives.

AT PRESENT IT IS UNCLEAR WHETHER OR NOT SCREENING SAVES THE LIVES OF WOMEN WHO DEVELOP OVARIAN CANCER.

What are the problems with screening for ovarian cancer?

False positive results are often found.
The major problem with screening for ovarian cancer is that both the CA 125 test and ultrasound scanning can be abnormal in a proportion of women who do not have cancer of the ovary. These sorts of results, known as 'false positives', are a serious problem as they can cause a great deal of anxiety. Even worse, if the abnormalities persist, it may ultimately be necessary to perform an operation to remove the ovaries and tubes in order to exclude the possibility of ovarian cancer which turns out to have been unnecessary. As ovarian cancer is relatively uncommon it works out that more abnormal screening results are due to false positive findings than are due to cancer.

False negative results can occur.
Most women find a normal screening result reassuring. However, it should be recognised that neither CA 125 or ultrasound will pick up every case of ovarian cancer. 'False negative' results do occur and a small number of women will be falsely reassured.

What studies are in progress?

Studies of women in the general population.

An extremely ambitious study of ovarian cancer screening has been set up in the UK. The study is called UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) and involves 202,638 women aged 50-74 years from 13 regional centres. UKCTOCS is a randomised trial, which means that women who agree to take part were randomly allocated to be screened with either CA 125 or ultrasound, or to a control group who are followed up without screening. This randomisation is essential in order to obtain clear answers about how effective ovarian cancer screening is at saving lives.The study will finish in 2014 and will eventually provide information about the number of lives which can be saved by screening, the financial cost of screening, the psychological impact of screening and the problems caused by false positive results.

UKCTOCS is being co-ordinated by the research team at the Gynaecological Cancer Research Centre at University College Hospitall and is funded jointly by the Medical Research Council, Cancer Research UK and the Department of Health. Unlike previous screening studies, women did not volunteer to take part in UKCTOCS. Participation was by invitation from population registers to ensure that the results are representative of the whole population.

The UK Familial Ovarian Cancer Screening Study.- UKFOCSS

A national study is just being launched to assess and refine screening amongst women with a strong family history of ovarian cancer. A strong family history involves two or more close relatives with ovarian cancer or 1 relative with ovarian cancer and a relative with breast cancer which occurred at a young age (<50 years). Women who think that they fall into this category should ask their GP for advice and may be referred to a specialist genetics centre for the family history to be confirmed. Most regional genetics centres will know how to enrol eligible women into the familial screening study which involves a CA 125 test every four months and an ultrasound scan once a year.

The UK Familial Ovarian Cancer Screening Study.- UKFOCSS

A national study is just being launched to assess and refine screening amongst women with a strong family history of ovarian cancer. A strong family history involves two or more close relatives with ovarian cancer or 1 relative with ovarian cancer and a relative with breast cancer which occurred at a young age (<50 years).

Women who think that they fall into this category should ask their GP for advice and may be referred to a specialist genetics centre for the family history to be confirmed. Most regional genetics centres will know how to
enrol eligible women into the familial screening study which involves an annual CA 125 test and ultrasound scan.

Screening and you

Many women are concerned about their risk of developing ovarian cancer, particularly if they have a friend or relative who has developed the cancer. It is understandable that many women with this first-hand experience of ovarian cancer wish to be screened. Currently the guideline in most countries state that screening should not be undertaken until more is learned about the pros and cons on screening. It is important to be aware of the limitations and disadvantages of current screening techniques that have been outlined above. Broad guidelines are provided below but the decision made by an individual woman will understandably be heavily influenced by her experience of ovarian cancer.

Women <50 years with no family history.
The risk of ovarian cancer to women less than 50 years of age is small and the risk of a false positive screening result is high. Screening is not recommended for this group of women.

Women >50 years with no family history.
There is at present no evidence that screening is of value to women in this age group and, as outlined above, there are definite disadvantages associated with screening. For this reason routine screening is not recommended. Women in this group may, however, be participating in one of the ongoing general population screening trials mentioned above.

Women with a weak family history.
Many women in this group will have one close relative who has developed ovarian cancer and will be understandably anxious about their own risk. The risk to women in this group is slightly but not greatly increased and the value of screening is uncertain. Most centres do offer advice and counselling to women with a weak family history. Ultimately the decision about screening must be an individual one after a careful explanation of the pros and cons. Women with a weak family history may be participating in the general population screening trials.

Women with a strong family history.
Women with a strong family history as outlined above are at substantially increased risk of ovarian cancer and may wish to participate in the UK Familial Ovarian Cancer Screening Study. This group of women should have access to expert advice about prevention as well as screening through referral to a specialist centre. They may then be offered participation in the UK Familial Ovarian Cancer Screening Study.