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

By I. Jacobs, U. Menon, Andy Ryan, A. Gentry-Maharaj, M. Burnell, Jatinderpal K Kalsi, N. Amso, S. Apostolidou, E. Benjamin, Derek Cruickshank and 36 more. The Lancet, 2016

821 citations recorded by the source corpus.

Summary 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.

Subfields: Genetics, Oncology, Reproductive Medicine

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Citations in the corpus

Global Cancer in Women: Burden and Trends (2017, background): “…ultrasound plus biomarker testing in the United States and the United Kingdom (also including a risk algorithm study arm) found no mortality bene ﬁ t in average-risk women after about 15 years, although results indicated improvements with longer follow-up; future analyses are planned (94, 95).”
The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded. (2016, background): “Over the past two decades, clinical screening trials, primarily using transvaginal ultrasonography and serum cancer antigen 125 concentrations, have not shown a survival benefit.(87,88) Their goal was to detect stage I disease (confined to the ovary) because studies have shown 90% survival for women”
Biological roles of glycans (2016, background): “The value of such markers for early detection remains unclear (952), a problem known to plague many predictive serum markers (953).”
Ovarian Cancer Statistics, 2018 (2018, neutral): “The UK Collaborative Trial of Ovarian Cancer Screening, another large randomized trial based in the United Kingdom, evaluated TVU combined with a risk algorithm incorporating changes in CA 125 levels and found reduced mortality in average-risk women after 15 years.(79) However, the use of secondary ”
Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening (2018, methodology): “A promising approach to ovarian cancer screening has been demonstrated by the UK Collaborative Trial of Ovarian Cancer Screening, which currently is assessing the efficacy of a multimodal screening strategy (MMS) including annual CA 125 screening using a risk of ovarian cancer algorithm and TVU as a”