Potential of ovarian cancer screening to save lives

Here, Dr Seif, shares his experiences and insights gained as Manchester Lead for the iconic UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) trial.  Dr Seif was also on the ultrasound subcommittee and publication writing group for the study.

An estimated 240,000 women worldwide are diagnosed with ovarian cancer each year.
Of these over 140 are likely to die of the condition.  Ovarian cancer has been described as the silent killer as the indigestion, swollen stomach and other symptoms associated with the condition only appear at a late stage (stage 3/4).  By this time the cancer has grown larger, is starting to spread, and the only treatment option available is chemotherapy, which brings a poor quality of life – including a loss of appetite, diarrhoea, nausea – and just a 10–15% chance of survival.

In comparison, the survival rate for those treated at stage 1, where the cancer is isolated to the ovaries, is over 80%, so we knew that the ability to detect the cancer earlier was key to better outcomes for women.

The UKCTOCS study is part of a programme of work that started 30 years ago based on the hypothesis that a protein called CA125, in combination with ultrasound, could present the basis of a screening test.  UKCTOCS was a 15-year study of 200,000 post-menopausal women with no symptoms of ovarian cancer aged 50 to 74 years from across 13 centres in the UK.

My team at Saint Mary’s Hospital was delighted to be the Manchester centre for UKCTOCS.  We have a strong track record in gynaecological research and introduced the UKCTOCS trial in Manchester in 2001.

CMFT responsible for the largest clinical study ever in the North West

As one of the largest trials ever performed, centres across the UK first needed to recruit a large number of women to participate in the study and then needed to scale up their capacity to provide the regular assessment visits required.

In Manchester, we successfully recruited 16,500 women into the study.  This success is in part due to the willingness and generosity of participants at Saint Mary’s Hospital, who gave up their time.  Our foresight to employ and comprehensively train highly qualified sonographers especially for this study also brought efficiencies to our ability to deliver the study.  The study involved coordinating a large number of technical specialities – research nurses, sonographers, and administrative staff, including financial management.

Our agile approach to resourcing the study delivery team in Manchester and NIHR support key to success

The support of the NIHR also played a vital role: the NIHR / Wellcome Trust Manchester Clinical Research Facility provided a dedicated clinic which could accommodate the high footfall of participants.  The CRF delivered the protocol and quality assurance required for the study,, and NIHR-funded nursing staff supported the delivery of the assessment visits.

What do the study results mean for patients?

The study demonstrated:

• Increased accuracy of a new statistical calculation (Risk of Ovarian Cancer Algorithm; ROCA) to interpret changing levels in women’s blood of a protein called CA125 in predicting a woman’s individual risk of developing cancer, compared to the conventional screening method which uses a fixed ‘cut-off’ point for CA125.  The new method detected cancer in 86% of women with invasive epithelial ovarian cancer (iEOC), whereas the conventional test used in previous trials or in clinical practice would have identified fewer than half of these women (41% or 48% respectively).
• A impact on mortality rates between the screening and control arms, which became more evident after the first seven years of the trial.  The study suggests that screening reduces the number of women dying from ovarian cancer by around 20%.

The research team are now following up the study for three more years to establish the full impact of an ovarian cancer screening programme.  Estimates from the results so far are promising, but the exact figures remain uncertain.

The ROCA has been licensed to Abcodia Ltd, a UCL spin out company, with which Dr Seif has a paid consultancy role.