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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
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posted on 2023-06-10, 02:19 authored by Usha Menon, Aleksandra Gentry-Maharaj, Matthew Burnell Burnell, Naveena Singh, Andy Ryan, Chloe Karpinskyj, Giulia Carlino, Julie Taylor, Susan K Massingham, Maria Raikou, Jatinderpal Kalsi, Robert Woolas, Ranjit Manchanda, Rupali Arora, Lesley FallowfieldLesley Fallowfield, othersBackground 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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Publication status
- Published
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- Published version
Journal
The LancetISSN
0140-6736Publisher
ElsevierExternal DOI
Issue
10290Volume
397Page range
2182-2193Event location
EnglandDepartment affiliated with
- Sussex Health Outcomes Research & Education in Cancer (SHORE-C) Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-01-17First Open Access (FOA) Date
2022-01-17First Compliant Deposit (FCD) Date
2022-01-17Usage metrics
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