UKCTOCS

Long term impact of screening on ovarian cancer mortality in the UK Collaborative Trial of Ovarian Cancer Screening

Does screening for ovarian cancer help save lives by detecting the disease earlier?

What is this study about?

Ovarian cancer is the leading cause of death from gynaecological cancers in the UK. This is related to diagnosis at advanced stage. When women are diagnosed earlier, they have a much better survival – over 90% of Stage I patients are alive five years after diagnosis compared to 4% of Stage IV patients. This suggests that screening may help save lives by detecting the disease earlier.

The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was designed to test this hypothesis. Between April 2001-Sept 2005, 202,638 postmenopausal women, aged 50-74 years were recruited through 13 trial centres in England, Wales and Northern Ireland. Women were randomly allocated to one of three groups (i) control (C ) - no screening (ii) multimodal screening (MMS) - annual blood test for serum CA125 measurement. The results were interpreted using the ‘Risk of Ovarian Cancer Algorithm’, with transvaginal ultrasound as a second line test in case of abnormality (iii) ultrasound screening (USS) – annual and second line tests were transvaginal scans.

Women in the screen arms underwent a total of 673,765 annual screens till 31st December 2011. On 31st Dec 2015 at a median follow-up of 11.1 years per woman the initial mortality analysis was undertaken. Compared to the control group there was significant increase in number of women diagnosed with early stage ovarian cancer in the multimodal but not in the ultrasound group. The average reduction in ovarian cancer deaths was 15% in multimodal group and 11% in ultrasound group compared to control but this was not definitive. The final extent of reduction remains to be determined as the ovarian cancer death rates were increasing in the control group and levelling off in the multimodal and ultrasound groups.

Follow-up will now continue till 31st Dec 2018 when a second mortality and cost effectiveness analysis will be undertaken.

Women are linked via their individual NHS numbers to national cancer and death registries in England, Wales and Northern Ireland as well as administrative databases such as Hospital Episode Statistics and National Cancer Intelligence Network. Records of women identified as having a possible ovarian cancer based on a specified list of disease codes will be retrieved and reviewed by an independent outcomes committee who will confirm final outcome. Data from other national databases such as Hospital Episodes statistics will be used to calculate the cost of screening.

 

The mortality results of UKCTOCS, the largest ever ovarian cancer screening trial, were published in The Lancet in December 2015. In the trial women underwent one of two forms of screening (1) multimodal screening (MMS) based on a yearly CA125 blood test interpreted using the Risk of Ovarian Cancer Algorithm (ROCA) followed by an internal (transvaginal) scan and repeat blood test if the result was abnormal (2) ultrasound screening (USS) based on a yearly internal scan which was repeated if the result was abnormal. They were offered between 7-11 annual screens. The ovarian cancer outcomes till 31st December 2014 of women in the screen groups were compared to those of women in the control (C) group who were not offered any screening.

The trial showed for the first time that multimodal screening results in the detection of significantly more earlier stage ovarian/peritoneal cancers than no screening. It may be possible to prevent 1 in 5 (20%) ovarian cancer deaths if women undergo annual multimodal screening (MMS) but this needs to be confirmed on further follow up.

For every woman found to have ovarian cancer on screening, 2 additional women in the MMS group and 10 additional women in the USS arm had surgery where the ovaries were only found to have benign lesions or were normal. The surgical complication rate of these additional operations was around 3.1% (MMS) and 3.5% (USS) which matches the standard complication rate for such surgery. In addition, while screening did not raise anxiety, levels of worry were higher in women who had abnormal results and required additional 2nd line tests. Rarely women had complications related to having a blood test or an internal scan such as pain, bruising or cystitis.

Our data at this point is not sufficient to recommend a National Screening Programme like for breast and cervical cancer. We estimate that further follow-up of approximately four years is required before we can confirm the reduction in deaths. However, we remain hopeful that following this time period we will be able to provide the National Screening Committee with all the information they need to make a decision as to whether the NHS should have an ovarian cancer screening programme.

The UKCTOCS data provide fresh impetus to continue to pursue screening as an option for reducing mortality in this most lethal of gynaecological cancers. We are greatly indebted to our trial participants, the funding agencies and the many NHS staff who have brought us so far.

Jacobs IJ, Menon U, Ryan A. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 2015; published online Dec 17. (Click the link to access the published scientific article).

A meeting was held at the Royal College of Obstetrics and Gynaecology to present the results. The meeting was recorded and can be viewed by clicking on the following link:-

 

Various media outlets reported on the results

Telegraph

BBC News

Daily Express

The Guardian

Type of study

Randomised trial

Where is it taking place?

13 trial centres in England, Wales and Northern Ireland.

Who is included?

Postmenopausal women, aged 50-74 years