Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial
Open accessAbstract
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.
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Longitudinal CA125 measurements combined with transvaginal ultrasonography improve positive predictive value for ovarian cancer detection, but the benefit of screening is still elusive.
“Longitudinal CA125 measurements combined with transvaginal ultrasonography, result in improved PPV for ovarian cancer detection, but the benefit of screening is still elusive9,10.”
From Detection of ovarian cancer via the spectral fingerprinting of quantum-defect-modified carbon nanotubes in serum by machine learning (2022) · cites this paper as [9]
Model performance of the sensor technology exceeds the results of the current best clinical screening test using longitudinal CA125 and second-line transvaginal ultrasonography (87% vs 84% clinical sensitivities at 98% specificity).
“Model performance of the sensor technology exceeds the results of the current best clinical screening test using longitudinal CA125 and second-line transvaginal ultrasonography9 (87% vs 84% clinical sensitivities at 98% specificity).”
From Detection of ovarian cancer via the spectral fingerprinting of quantum-defect-modified carbon nanotubes in serum by machine learning (2022) · cites this paper as [9]
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- Authors
- Jacobs, I. J., Menon, U., Ryan, A., Gentry-Maharaj, A., Burnell, M., Kalsi, J. K., Amso, N. N., Apostolidou, S., Benjamin, E., Cruickshank, D., Crump, D. N., Davies, S. K., Dawnay, A., Dobbs, S., Fletcher, G., Ford, J., Godfrey, K., Gunu, R., Habib, M., Hallett, R., Herod, J., Jenkins, H., Karpinskyj, C., Leeson, S., Lewis, S. J., Liston, W. R., Lopes, A., Mould, T., Murdoch, J., Oram, D., Rabideau, D. J., Reynolds, K., Scott, I., Seif, M. W., Sharma, A., Singh, N., Taylor, J., Warburton, F., Widschwendter, M., Williamson, K., Woolas, R., Fallowfield, L., McGuire, A. J., Campbell, S., Parmar, M., & Skates, S. J.
- Affiliations
- University of Manchester (GB)
- University College London (GB)
- Cardiff University (GB)
- James Cook University Hospital (GB)
- University College Hospital (GB)
- Belfast City Hospital (GB)
- Queen Elizabeth Hospital (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Bangor University (GB)
- Liverpool Women's Hospital (GB)
- Royal Derby Hospital (GB)
- Derriford Hospital (GB)
- St Michael's Hospital (GB)
- St Bartholomew's Hospital (GB)
- Massachusetts General Hospital (US)
- University Hospital of Wales (GB)
- National Health Service (GB)
- Public Health England (GB)
- Nottingham City Hospital (GB)
- Queen Alexandra Hospital (GB)
- Brighton and Sussex Medical School (GB)
- London School of Economics and Political Science (GB)
- MRC Clinical Trials Unit at UCL (GB)
- Harvard University (US)
- Corresponding author
- Jacobs, Ian J
- Menon, Usha
- ORCID
- Jacobs, Ian J
- Menon, Usha
- Ryan, Andy
- Burnell, Matthew
- Kalsi, Jatinderpal K
- Amso, Nazar N
- Apostolidou, Sophia
- Dawnay, Anne
- Gunu, Richard
- Karpinskyj, Chloe
- Leeson, Simon
- Lopes, Alberto
- Mould, Tim
- Rabideau, Dustin J
- Sharma, Aarti
- Singh, Naveena
- Taylor, Julie
- Warburton, Fiona
- Widschwendter, Martin
- Williamson, Karin
- Fallowfield, Lesley
- McGuire, Alistair J
- Campbell, Stuart
- Parmar, Mahesh
- Skates, Steven J
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 387
- Issue
- 10022
- Pages
- 945-956
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC4779792
- OpenAlex
- W2214802907
- Cited by
- 1,048
- References
- 40
- Citations by year
- 2026: 35 · 2025: 70 · 2024: 116 · 2023: 82 · 2022: 99 · 2021: 111 · 2020: 103 · 2019: 114 · 2018: 105 · 2017: 129 · 2016: 78 · 2015: 2 · 2014: 2
- FWCI
- 119.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Lancet (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- London School of Economics and Political Science Research Online (London School of Economics and Political Science) (acceptedVersion)
- London School of Economics and Political Science Theses Online (London School of Economics and Political Science) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- Funders
- Medical Research Council (G9901012 and G0801228)
- Cancer Research UK (C1479/A2884)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- ovarian cancer screening, ovarian cancer mortality, multimodal screening, transvaginal ultrasound, CA125, early detection, postmenopausal women, screening effectiveness, bilateral oophorectomy
- MeSH terms
- Aged, Algorithms, Female, United Kingdom, Humans, Membrane Proteins, Middle Aged, Ovarian Neoplasms, Proportional Hazards Models, Outcome Assessment, Health Care, CA-125 Antigen, Early Detection of Cancer
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