Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial
Open accessAbstract
BACKGROUND: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS. METHODS: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032. FINDINGS: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group. INTERPRETATION: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended. FUNDING: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.
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In ovarian cancer, established serum biomarkers are highly specific but insufficiently sensitive to detect early-stage disease and to impact mortality.
“In ovarian cancer, the few established serum biomarkers are highly specific, yet insufficiently sensitive to detect early-stage disease and to impact the mortality rates of patients with this cancer.”
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 [10]
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 [10]
Currently, no screening strategy can identify ovarian cancer at an early enough stage to reduce mortality.
“Currently, no screening strategy can identify disease at an early enough stage to reduce mortality10.”
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 [10]
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- Authors
- Menon, U., Gentry-Maharaj, A., Burnell, M., Singh, N., Ryan, A., Karpinskyj, C., Carlino, G., Taylor, J., Massingham, S. K., Raikou, M., Kalsi, J. K., Woolas, R., Manchanda, R., Arora, R., Casey, L., Dawnay, A., Dobbs, S., Leeson, S., Mould, T., Seif, M. W., Sharma, A., Williamson, K., Liu, Y., Fallowfield, L., McGuire, A. J., Campbell, S., Skates, S. J., Jacobs, I. J., & Parmar, M.
- Affiliations
- MRC Clinical Trials Unit at UCL (GB)
- Barts Health NHS Trust (GB)
- University College London (GB)
- University of Piraeus (GR)
- Queen Alexandra Hospital (GB)
- Queen Mary University of London (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- Belfast City Hospital (GB)
- Ysbyty Gwynedd Hospital NHS Trust (GB)
- St Mary's Hospital (GB)
- University Hospital of Wales (GB)
- Nottingham City Hospital (GB)
- Massachusetts General Hospital (US)
- Brighton and Sussex Medical School (GB)
- London School of Economics and Political Science (GB)
- Harvard University (US)
- UNSW Sydney (AU)
- Corresponding author
- Menon, Usha
- ORCID
- Menon, Usha
- Burnell, Matthew
- Singh, Naveena
- Ryan, Andy
- Karpinskyj, Chloe
- Taylor, Julie
- Raikou, Maria
- Kalsi, Jatinderpal K
- Manchanda, Ranjit
- Arora, Rupali
- Dawnay, Anne
- Leeson, Simon
- Mould, Tim
- Sharma, Aarti
- Williamson, Karin
- Liu, Yiling
- Fallowfield, Lesley
- McGuire, Alistair J
- Campbell, Stuart
- Skates, Steven J
- Jacobs, Ian J
- Parmar, Mahesh
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 397
- Issue
- 10290
- Pages
- 2182-2193
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC8192829
- OpenAlex
- W3162975920
- Cited by
- 730
- References
- 30
- Citations by year
- 2026: 120 · 2025: 146 · 2024: 161 · 2023: 144 · 2022: 130 · 2021: 29
- FWCI
- 99.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- London School of Economics and Political Science Research Online (London School of Economics and Political Science) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Funders
- Cancer Research UK
- National Institute for Health Research
- 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, transvaginal ultrasound, multimodal screening, ovarian cancer mortality, fallopian tube cancer, postmenopausal women, long-term follow-up, screening effectiveness, ovarian cancer incidence, ovarian cancer risk factors
- MeSH terms
- Carcinoma, Ovarian Epithelial, Aged, Female, United Kingdom, Humans, Longitudinal Studies, Middle Aged, Ovarian Neoplasms, Registries, State Medicine, Ultrasonography, CA-125 Antigen, Early Detection of Cancer
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