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Lancet. 2016 Mar 5;387(10022):945-956. doi: 10.1016/S0140-6736(15)01224-6. Epub 2015 Dec 17.

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

Author information

1
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; University of New South Wales, Sydney, NSW, Australia; Centre for Women's Health, Institute of Human Development, University of Manchester, Manchester, UK. Electronic address: i.jacobs@unsw.edu.au.
2
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK. Electronic address: u.menon@ucl.ac.uk.
3
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK.
4
Obstetrics and Gynaecology, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK.
5
Research Department of Pathology, Cancer Institute, University College London Hospital, London, UK.
6
Department of Gynaecological Oncology, James Cook University Hospital, Middlesbrough, UK.
7
Clinical Biochemistry, University College London Hospital, London, UK.
8
Department of Gynaecological Oncology, Belfast City Hospital, Belfast, UK.
9
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Malomatia (Information, Communication and Technology QATAR) Qatari Shareholding Company, Qatar.
10
Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK.
11
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK.
12
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; School of Medical Sciences, Bangor University, Bangor, Gwynedd, UK.
13
Department of Gynaecology, Liverpool Women's Hospital, Liverpool, UK; Women's Hospital, Hamad Medical Corporation, Doha, Qatar.
14
Department of Gynaecological Oncology, Royal Derby Hospital, Derby, UK.
15
Department of Gynaecological Oncology, Llandudno Hospital, Gwynedd, UK.
16
Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK; Derriford Hospital, Plymouth, Devon, UK.
17
Department of Gynaecological Oncology, University College London Hospital, London, UK; Department of Gynaecological Oncology, Royal Free Hospital, London.
18
Department of Gynaecological Oncology, St Michael's Hospital, Bristol, UK.
19
Department of Gynaecological Oncology, St Bartholomew's Hospital, London, UK.
20
Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
21
Central Manchester Foundation Trust, St Mary's Hospital, Manchester, UK; Institute of Cancer Sciences, University of Manchester, Manchester, UK.
22
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Department of Gynaecological Oncology, University Hospital of Wales, Heath Park, Cardiff, UK.
23
Department of Pathology, Barts Health National Health Service Trust, London, UK.
24
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Public Health England, London, UK.
25
Department of Gynaecological Oncology, Nottingham City Hospital, Nottingham, UK.
26
Department of Women's Cancer, Institute for Women's Health, University College London, London, UK; Department of Gynaecological Oncology, Queen Alexandra Hospital, Portsmouth, Hampshire, UK.
27
Sussex Health Outcomes Research and Education in Cancer, Brighton and Sussex Medical School, University of Sussex, Sussex, UK.
28
Department of Social Policy, London School of Economics, London, UK.
29
Create Health Clinic, London, UK.
30
Medical Research Council Clinical Trials Unit at University College London, London, UK.
31
Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Erratum in

Abstract

BACKGROUND:

Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect 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 computer-generated 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 flexible parametric model showed that in the MMS group, this mortality effect 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 different 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 significant in the primary analysis, we noted a significant 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-effectiveness of ovarian cancer screening.

FUNDING:

Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

PMID:
26707054
PMCID:
PMC4779792
DOI:
10.1016/S0140-6736(15)01224-6
[Indexed for MEDLINE]
Free PMC Article

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