Please note that we are no longer recruiting volunters onto the trial as we have achieved our target of 200,000

Large studies performed by our research team and other international teams during the last decade have developed and refined two methods of screening. One method uses ultrasound scanning, similar to the scanning used in pregnancy, to check for any enlargement or abnormality of the ovaries. Ultrasound is currently widely used for diagnosing ovarian cancer in women with symptoms. It has been shown that the ultrasound test can be abnormal in the early stage of many ovarian cancers. This trial will use a method of ultrasound scanning called "transvaginal scan" whereby a probe is inserted into the vagina to see the ovaries. This method of scanning gives a much clearer picture of the ovaries than a transabdominal scan, where the probe is placed on the abdomen. The second method involves a blood test to measure a substance called CA 125. Most women who develop ovarian cancer have high levels of the protein called CA125 in their blood. The CA125 test is therefore currently used to diagnose ovarian cancer in women with symptoms and to monitor women after treatment. It has been shown that the CA125 test can be elevated in the early stage of many ovarian cancers. In addition, the research team believes that it may be possible to identify those women with early ovarian cancer where the CA125 blood test is not elevated by looking for changes i.e. increases in a woman's blood results over time.

Using these tests it seems likely that over 80% of women with ovarian cancer can be identified before they have symptoms. This current very large trial will answer the question whether early detection of ovarian cancer, using these tests can save the lives of women who have ovarian cancer.

Because we do not know if either of the screening methods are able to save lives from ovarian cancer we need to compare both methods of screening with a group of women who will not be screened. This will tell us whether screening can save lives and which method is most effective. This is called a randomised trial. The groups are randomly selected by a computer. Of the 200,000 women who agree to participate half will be screened every year for 6 years and half will be in the control group and followed up with questionnaires without screening. Overall the study will take 10 years to complete. Each participant will be followed up for 6 years. Of the 100,000 women who will be screened 50,000 will be screened with ultrasound and 50,000 with the CA 125 blood test.

The study will also assess the cost implications of the screening methods to the National Health Service (NHS), what anxieties and fears being screened may raise and what complications might arise as a result of screening. This information will be used to make a decision about whether an NHS national screening programme for ovarian cancer should be introduced.

The results will be reviewed by other medical professionals and published in the medical press. Results will probably only be available within a 12 year period. Should either screening method prove to be of benefit the results will be presented to the government as a case for a national screening programme to be implemented. Participants will be notified in writing that the study has been completed and of the outcome. Individuals will not be identified in any publications.

• 50-74 years of age
• Postmenopausal, i.e. you should not have had a period within the past 12 months if you are not taking hormone replacement therapy (HRT). However, if you are taking HRT, you are still eligible to take part, if you have taken it for one year or more
• Not have both your ovaries removed at surgery. You can still take part if only one ovary was removed.
• Not have had surgery, chemotherapy or radiotherapy for any type of cancer within the past 12 months (excluding skin cancer).
• Not currently be taking part in any other screening programme for ovarian cancer.
• Not belong a to a family with a high risk of familial ovarian cancer. Such families have
  1. Two or more first degree relatives (mother, sister, daughter) with ovarian cancer.
  2. One first degree relative with ovarian cancer and one first degree relative with breast cancer diagnosed under 50 years of age.
  3. One first degree relative with ovarian cancer and two first or second first degree (grandmother, grand-daughter, aunt or niece) relatives with breast cancer diagnosed under 60 years of age.
  4. Three first degree relatives with cancer of the large intestine or bowel, with at least one diagnosed before the age of 50 years and at least one first degree relative with ovarian cancer.
  "If you do belong to such a family and are a first degree relative of the person with cancer you may be at slightly higher risk of developing ovarian cancer and require regular screening. If you are concerned about your risk of developing ovarian cancer further information can be obtained from the OVACOME (A support group for ovarian cancer patients and their families, tel: 01992-446306), Cancer BACUP (an information service about cancer, tel: 0808-800-1234) or your GP. "

Women who agree to take part in this study will be sent an information leaflet and an appointment to attend their regional centre for registration. At this appointment, the study will be discussed in greater detail and they will have the opportunity to ask any questions. Women who agree to participate will be asked to sign a consent form. A questionnaire will be completed and eligibility confirmed. A blood sample will be taken. Their General Practitioner will be informed of their participation.

A further questionnaire will be given for completion at home and return by post to assess the psychological implications of screening and the perception of risk of ovarian cancer. This should not take more than 10 minutes to complete. A small number of women, including those who have abnormal results on screening, will be sent repeat questionnaires which also assess the acceptability of the screening methods to complete at home during the course of the study.

For women allocated to either screened group there is no special preparation for either the blood test or the ultrasound scan.

The blood sample taken at the registration visit from women allocated to the CA125 group will be tested. Their potential risk of developing ovarian cancer (ROC) in the year following the blood test will be calculated. The ROC will be recalculated after each blood test. The ROC calculation is looking for changes in blood results over time. For this reason the recommended follow-up may vary during the course of the study but will be one of the following:

• If the ROC is within normal limits women will be asked to return for a further blood test in one year. Most women will fall into this group and be recalled annually throughout the study.
• If there is a slight change in the levels of the blood test the ROC will be classified as intermediate and those women will be asked to return for a repeat blood test 3 months later.
• If the ROC is higher than would be expected (elevated) those women will be sent an appointment for a further blood test and an ultrasound scan of their ovaries. It is important to note that most women who require an ultrasound scan will not have an abnormality of their ovary and will not require surgery. If the ultrasound scan does reveal an abnormality of the ovaries, those women will be referred to a specialist at the regional centre for further tests and surgery to remove their ovaries. This will be arranged in consultation with t he woman and their General Practitioner. Only 1 in 5 of the women who have an abnormal test and have surgery will have ovarian cancer. The others will usually have less serious conditions of the ovary.

Women allocated to the ultrasound group will be sent an appointment for a scan of their ovaries. If no abnormalities are detected on the scan they will be sent an appointment for a further scan in one year. If an abnormality is seen, those women will be sent an appointment for a repeat scan in 6-8 weeks. This is because many of the abnormalities will disappear on their own and need no treatment. If the repeat scan is normal those women will be recalled in one year. If the repeat scan shows that the changes seen in the first scan persist, they will be referred to a specialist at the regional centre for further tests and surgery to remove the ovaries. This will be arranged in consultation with the woman and their General Practitioner. Only 1 in 10 of the women who have an abnormality detected at ultrasound and have surgery will have ovarian cancer. The others will usually have non cancerous conditions of the ovary.

The blood test taken at the registration visit will not be tested but will be stored to be used at some stage in the future to assess potential tests for cancer. As these will be tests in the initial phases of being researched, the results will not be conclusive and therefore women will not be notified of any results.

Women will be notified by post of their recommended follow-up after every blood test or investigation.

• Some women may have ovarian cancer that has not been identified by the test and thus be falsely reassured. If women develop any symptoms that you are concerned about, you should see your doctor as soon as possible.
• CA125 is not a test for all types of cancer. You should continue with all routine screening e.g. smear tests and breast screening, as advised by your GP surgery.
• Women taking part in the study have a 1 in 70 chance of being referred for surgery on the basis of abnormal screening results.
• Of every 1,000 women who take part in this trial 20-30 will have a positive screening test leading to surgery but only 1-2 of these women will actually have ovarian cancer. Most of the other women will be found to have other less serious abnormalities at surgery (eg. ovarian cysts, endometriosis, scar tissue or infection). In a small number of women who undergo surgery no abnormality will be found at all.
• Not all women with ovarian cancer who are identified by the screening test will have early disease, the disease may be more advanced. The screening test may therefore not make a difference to the type of treatment a woman may receive or the outcome of the treatment.
• Having a screening test can create anxiety in some women.

• The only direct benefit of taking part for the women allocated to the questionnaire group is that we will request that they are referred to the specialist at the regional centre if their GP suspects that they may have an ovarian cancer. The participation of these women is however vital to the outcome of the study. Their participation will help decide whether either screening method is of benefit and whether a national screening programme should be implemented.
• If a woman allocated to the screened groups does have ovarian cancer, but no symptoms, there is at least a 80% chance that she would be identified by the test.
• If a woman allocated to the screened groups does not have cancer there is At least a 99.5% chance that the test will be negative and provide reassurance.

What if new information becomes available? There is an independent Data Monitoring and Ethics committee that will assess the trial on an ongoing basis. If any information should become available that makes this study unethical, then this committee will recommend to the Trial Steering Committee which also has an independent chairman and non medical representatives that the study be stopped.

Will taking part in this study be kept confidential? All information which is collected about participants during the course of the research will be kept strictly confidential. Occasionally the research documentation and results will be looked at by the people funding the research programme to check that the study is being carried out properly. Any information about participants which is viewed by people not directly related to the research team will have names and addresses removed so that women cannot be recognised from it.

• Q1. Why did the previous trials not establish the effectiveness of cancer screening?

  A1. The previous trials were not large enough (the single largest trial involved 22,000 women) to establish whether the early detection of ovarian cancer actually saved the lives of the women. These studies did establish was that there are two possible screening methods (a blood test for the substance CA 125 and ultrasound scanning of the ovaries) can effectively detect early ovarian cancer before the women develop symptoms.

• Q2. How will you recruit the 200,000 women needed for the trial and who will they be?

  A2. The 200,000 women in the study will be postmenopausal (12 months without periods) women between the ages of 50 and 74 years who do not have a strong family history of ovarian or breast cancer. They will be invited to take part from health authority registers of 12 regional centres around the UK. Recruitment will take 3 years.

• Q3 Why can women not volunteer for the trial?

  A3. Women will not be allowed to directly volunteer for the trial because
  1. It is important to eliminate all bias so that at the end of the study it is not claimed that screening saved more lives in the trial than it would in reality because the women who volunteered were more informed, had a healthier lifestyle, were from higher socio-economic groups or better organised health authorities.
  2. The number of invited women who actually agree to participate will allow some estimate to be reached of the proportion of women who would participate if ovarian cancer screening were to become a part of the NHS screening programme.

• Q4. How much money is the NHS putting into this trial and why do they need to contribute?

  A4. The NHS will provide about £12 million for the trial from a special research and development fund. All MRC funded research trials are funded in this manner. The MRC provides all the money for the research aspects of the study i.e. the collection and analysis of data while the NHS provides the money for the services which will continue even after the trial is over, if screening becomes standard NHS practise (e.g. the ultrasound and CA 125 blood test).

• Q5. What is a randomised trial?

  A5. This means that if a woman agrees to take part the decision about whether she will be screened and if so with which test, is a random decision. Neither she nor the trial organisers will be able to influence the decision. Randomisation is crucial to prevent bias in interpreting the trial results.

• Q6. What do you expect to get out of the trial?

  A6. At the end of this study we will have information about how many lives ovarian cancer screening can save, how much it will cost, what proportion of eligible women are likely to take part, how women feel about being screened and the complications of screening. This information will be used to make a decision about whether an NHS national screening programme for ovarian cancer should be introduced.

• Q7. Ten years is a long time, is there no likelihood of a cure before then?

  A7. It is hoped that over the next decade, newer drugs and strategies for treating advanced ovarian cancer will emerge. However, it will always be better, both for the individual woman and for the medical team treating her, if the cancer is detected in an early stage when it is confined to the ovaries and this is what we hope screening will achieve.

• Q8. Screening itself can be quite traumatic for many women. How will you deal with that?

  A8. 1. On the individual level, all women will have contact details of trial staff both nursing and medical, at their regional centre with whom they can discuss any worries that their screening results might generate.
  2. On a more formal research basis, a quality of life study is part of the overall trial to ensure that the anxiety generated as a result of screening is continuously monitored. The trial will assess the psychosocial impact of screening on women partaking in the study. The information obtained will be used to help women through the screening process and improve the measures taken to overcome the worries that women may encounter in future screening programmes.

• Q9 When will the recruitment of women start, and when will the trial start?

  A9 The trial will formally start in January 2001 and recruitment will take place in 12 regional centres across the UK. Each of the 12 centres will start recruitment at different times throughout 2001. The first recruitment clinic will be held at the first centre at the beginning of March 2001.

• Q10 What other trials are still under way, or will soon be under way regarding ovarian cancer screening?

  A10 The St Bartholomew's / Royal London study based on a blood test and the ERTOCS (European trial of ovarian cancer screening) study based on an ultrasound scan of the ovaries are the only ovarian cancer screening trials in the general population currently taking place in the UK. Both these trials are closed to recruitment but are continuing to screen participants at least until the end of 2001. It is not envisaged that there will be any other ovarian cancer screening trials in the general population in the UK once UKCTOCS starts. The only other large ovarian cancer screening study in the world is in the USA where screening for ovarian cancer is part of an ongoing screening trial which includes prostate, lung and large bowel cancer (NIH PLCO trial).

• Q11 What will happen to the women who are in the St Bartholomew's / Royal London study and the other UK ovarian cancer screening trial (ERTOCS)?

  A11 Women who are currently enrolled in the St Bartholomew's / Royal London study (pilot study) will continue to be screened as per protocol by the Ovarian Cancer Screening Unit at St Bartholomew's Hospital, London. The same will apply to women taking part in the ERTOCS, the only other ovarian cancer screening trial in the UK.

• Q12 What will happen to women who are found to have ovarian cancer?

  A12 Women who are suspected to have ovarian cancer as a result of screening, will be referred to the gynaecologist specialising in women's cancers in their region for further assessment. If further investigations suggest that an ovarian tumour is present, surgery with removal of the ovaries will be performed with a view to making a diagnosis and treating the ovarian cancer if it was confirmed. Many operations will be performed laparoscopically (keyhole surgery), although some women will require a laparotomy (open surgery).

• Q13 What is the current treatment for ovarian cancer

  A13 Currently, women diagnosed with ovarian cancer, first undergo an operation to remove their ovaries, tubes, uterus, omentum (this is an apron of fat present in the abdomen) and any enlarged lymph glands and other sites of tumour in their abdomen. Except for the minority of women who are found to have cancer confined to their ovaries, all the rest will then have chemotherapy for 6 cycles (this usually takes 18 weeks).

• Q14 The screening will involve either a blood test or an ultra sound test. What will this involve ?

  A14 1. If the woman is randomised to screening using a blood test, then she will have a small amount of blood taken by a nurse at her regional centre (similar to blood taken for routine tests). This will then be sent to the main study centre in London for analysis (of a substance called CA125 which is secreted by most ovarian cancers). She will be informed of her results by a letter. If the test is normal, she will be asked to return in 1 year for a repeat test. This will continue for 6 years. If the test is abnormal, she will be asked to attend for a vaginal ultrasound scan to look at her ovaries. If a swelling is detected in the ovaries, she will then be referred to a gynaecologist specialising in women's cancers for further tests and possibly surgery.
  2. If the woman is randomised to screening using an ultrasound scan test, then she will have a vaginal scan of her ovaries at her regional centre. If the scan is normal, she will be asked to return in 1 year for a repeat scan. This will continue for 6 years. If the test shows a swelling in the ovaries, she will be asked to attend for a second scan in a maximum of 8 weeks. If the swelling has not disappeared, she will be referred to a gynaecologist specialising in women's cancers for further tests and possibly surgery.

• Q 15 Why is there a need for two type of tests?

  A 15 There are two ways of initially screening (blood test and scan) for ovarian cancer. Both can detect ovarian cancer in the early stages. We are studying both types of screening so that at the end of the study it will be possible to decide which type of testing detects more cancers, is more convenient and comfortable for the women, results in lower false positive rates (less women who do not have ovarian cancer being detected as possibly having cancer) and is more cost effective.

• Q16 From the trial results, how will the researchers know which screening method will be the best one to use.

  A16 At the end of the trial, there will be a direct comparison of the results of the two methods of screening. We will know which screening method (blood test or scan) detected more cancers, was more convenient and comfortable for the women, had lower false positive rates (less women who do not have ovarian cancer being detected as possibly having cancer) and was more cost effective.

• Q17 If the trial results show that a screening programme for ovarian cancer is efficient, what is the next stage, and how long will it take before it becomes common practise?

  A17 If the trial results show that a screening programme for ovarian cancer saves lives, it would then be over to the NHS executive and other government bodies to decide about making it available to all women in the same manner as the breast and cervical screening programme.