Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Jacobs, Ian J, Menon, Usha, Ryan, Andy, Gentry-Maharaj, Aleksandra, Burnell, Matthew, Kalsi, Jatinderpal, Amso, Nazar N, Apostolidou, Sophia, Benjamin, Elizabeth, Cruickshank, Derek, Crump, Danielle N, Davies, Susan K, Dawnay, Anne, Dobbs, Stephen, Fletcher, Gwendolen, Ford, Jeremy, Godfrey, Keith, Gunu, Richard, Habib, Mariam, Hallett, Rachel, Herod, Jonathan, Jenkins, Howard, Karpinskyj, Chloe, Leeson, Simon, Lewis, Sara J, Liston, William R, Lopes, Alberto, Mould, Tim, Murdoch, John, Oram, David, Rabideau, Dustin J, Reynolds, Karina, Scott, Ian, Seif, Mourad W, Sharma, Aarti, Singh, Naveena, Taylor, Julie, Warburton, Fiona, Widschwendter, Martin, Williamson, Karin, Woolas, Robert, Fallowfield, Lesley, McGuire, Alistair J, Campbell, Stuart, Parmar, Mahesh and Skates, Steven J (2015) Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. ISSN 0140-6736

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Abstract

Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial
to establish the eff ect of early detection by screening on ovarian cancer mortality.

Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in
National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computergenerated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032.

Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS,
50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no
screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening
episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in 1282 (0·6%) women:
338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0–14 of 15% (95% CI –3 to 30; p=0·10) with MMS and 11% (–7 to 27; p=0·21) with USS. The Royston-Parmar fl exible parametric model showed that in the MMS group, this mortality eff ect was made up of 8% (–20 to 31) in years 0–7 and 23% (1–46) in years 7–14, and in the USS group, of 2% (–27 to 26) in years 0–7 and 21% (–2 to 42) in years 7–14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly diff erent death rates (p=0·021), with an overall average mortality reduction of 20% (–2 to 40) and a reduction of 8% (–27 to 43) in years 0–7 and 28% (–3 to 49) in years 7–14 in favour of MMS.

Interpretation Although the mortality reduction was not signifi cant in the primary analysis, we noted a signifi cant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7–14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-eff ectiveness of ovarian cancer screening.

Item Type: Article
Keywords: Ovarian Cancer, population screening
Schools and Departments: Brighton and Sussex Medical School > Sussex Health Outcomes Research & Education in Cancer (SHORE-C)
Subjects: R Medicine > R Medicine (General) > R852 Research. Experimentation > R853.C55 Clinical trials
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Kathryn Monson
Date Deposited: 21 Dec 2015 14:55
Last Modified: 07 Mar 2017 09:53
URI: http://sro.sussex.ac.uk/id/eprint/58900

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Project NameSussex Project NumberFunderFunder Ref
UKCTOCSG0543Medical Research CouncilG000073
UnsetUnsetCancer Research UKUnset
UnsetUnsetDepartment of HealthUnset
UnsetUnsetThe Eve AppealUnset