Contact information
Type
Scientific
Primary contact
Prof Usha Menon
ORCID ID
http://orcid.org/0000-0003-3708-1732
Contact details
Study contact for randomised controlled trial and follow up study
Gynaecological Cancer Research Centre
Department of Women’s Cancer
Institute of Women’s Health
UCL
1st floor
Maple House
149 Tottenham Court Road
London
W1T 7DN
United Kingdom
+44 (0)203 447 2108
u.menon@ucl.ac.uk
Type
Scientific
Additional contact
Prof Ian Jacobs
ORCID ID
Contact details
Study contact for randomised controlled trial only
University of New South Wales
Sydney
NSW 2052
Australia
+61 (0)2 93851000
i.jacobs@unsw.edu.au
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00058032
Protocol/serial number
Current Version 7.1
Study information
Scientific title
UK Collaborative Trial of Ovarian Cancer Screening
Acronym
UKCTOCS
Study hypothesis
Current hypothesis as of 01/10/2015:
Hypothesis 1 – Preclinical detection by screening can reduce mortality from Ovarian Cancer (OC).
Hypothesis 2 - OC mortality can be reduced without unacceptable physical and psychological morbidity.
Hypothesis 3 - OC mortality can be reduced at an acceptable economic cost to the health service.
Hypothesis 4 - If population screening for OC were introduced compliance would be high enough for an impact on overall mortality from OC to be achievable
Original hypothesis:
1. To establish the impact of preclinical detection of ovarian cancer by screening on ovarian cancer mortality
2. To determine the physical morbidity of ovarian cancer screening
3. To determine the resource implications of screening and the interventions which result from screening
4. To record the psychological consequences of screening in the subgroups of true negative, true positive, false negative and false positive screening results
5. To assess the feasibility of population screening for ovarian cancer as reflected by uptake of invitations and compliance rates with annual screening
6. To compare the performance of two screening strategies for ovarian cancer
7. To establish a serum bank for future assessment of novel tumour markers
Ethics approval
North West Medical Research and Ethics Committee, 21/06/2000, ref: 00/8/034
Study design
Part 1: Randomised controlled trial
Part 2: Observational longitudinal follow up study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Condition
Ovarian/tubal and primary peritoneal cancer
Intervention
Randomised controlled trial:
Three groups:
1. A control group (no screening)
2. A multimodal group (annual screening with serum CA125 interpreted using the Risk of Ovarian Cancer Algorithm (ROCA) as the primary test and CA125 and ultrasound as the secondary test)
3. An ultrasound group (annual screening with ultrasound as the primary test and repeat ultrasound in 6 - 8 weeks as the secondary test)
Observational longitudinal follow up study:
Eligible women will be followed up through national cancer and death registries and hospital administrative databases via data linkage using their NHS number till 31st June 2019. Quality of life questionnaires will be send to women newly diagnosed with ovarian cancer
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Randomised controlled trial:
Ovarian cancer mortality at 7 years after randomisation.
Correct as of 04/01/2017:
Death due to ovarian cancer, defined by WHO 2003 criteria, as determined by independent outcomes committee review of patient notes of all women identified through data linkage and postal follow-up to have a ‘possible ovarian cancer’ (pre-specified list of International Classification of Disease codes) till 31st December 2014.
Observational longitudinal follow up study:
Death due to ovarian cancer, defined by WHO 2014 criteria as determined by independent outcomes committee review of patient notes of all women identified through data linkage to have a ‘possible ovarian cancer’ (pre-specified list of International Classification of Disease codes) till 31st December 2018.
Secondary outcome measures
Randomised controlled trial:
Correct as of 04/01/2017:
1. Performance characteristics: Sensitivity, specificity, positive predictive values of the two screening strategies (multimodal and ultrasound) for detection of ovarian cancer diagnosed within one year of last screen. Ovarian cancer diagnosis is based on outcomes review of medical notes of all women who developed ovarian cancer during the trial.
2. Surgical complications in women who underwent false positive surgery and were found to have benign or normal adnexae. This is assessed through central medical note review and assigned by designated trial gynaecological oncologist.
3. Cost-effectivenesss of the multimodal (MMS) and ultrasound screening (USS) strategies separately comparing them to a no-screening arm:
3.1. Incremental cost-effectiveness analysis over the 14 year period of the trial (censorship 31st Dec 2014)
3.2. Incremental cost-effectiveness analysis for the cumulative mortality estimated over a 25-year period by extrapolating beyond the 14 years of the trial
4. Compliance with annual screening: The proportion of women who attended all tests that formed part of an annual screening episode of the total who were eligible for that annual screening episode. Psychological morbidity related to screening - assessed in a separate MRC funded study, UKCTOCS Psychosocial study, PI Prof Dame Lesley Fallowfield.
Added 01/10/2015:
1. Performance characteristics of the two screening strategies (serum CA125 versus ultrasound)
2. Physical morbidity resulting from surgical intervention attributable to screening
3. Psychological consequences of screening
4. Resource implications of screening and the resulting interventions
5. Feasibility of screening, as reflected by compliance rates with annual screening
6. Establish a serum bank for future assessment of novel tumour markers
Observational longitudinal follow up study:
Cost-effectiveness of ovarian cancer screening: This will be assessed using individual patient data from English (Hospital Episodes Statistics), Welsh (Patient Episode Database for Wales) and Northern Ireland hospital administrative databases. The data will be augmented with resource data collected on individual diagnostic tests and treatment through medical record review. All unit costs will be based on NHS Reference Costs with additional costs as reported by the relevant Personal Social Services Research Unit Cost exercise.
Overall trial start date
04/11/2000
Overall trial end date
31/12/2024
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged 50 - 74 years
2. Postmenopausal: either
2.1. Greater than 12 months amenorrhoea following a natural menopause or hysterectomy, or
2.2. Greater than 12 months of hormone replacement therapy (HRT) commenced for menopausal symptoms
Participant type
Healthy volunteer
Age group
Adult
Gender
Female
Target number of participants
200,000: Randomised - 202, 638; Eligible - 202, 546
Participant exclusion criteria
1. History of bilateral oophorectomy
2. Currently active non-ovarian malignancy. Women who have a past history of malignancy will only be eligible if:
2.1. They have no documented persistent or recurrent disease, and
2.2. They have not received treatment for more than 12 months
3. Women who have had an ovarian malignancy in the past
4. Women at high risk of ovarian cancer due to familial predisposition as defined by the eligibility criteria for the UK Familial Ovarian Cancer Screening Study (UKFOCSS)
5. Women participating in other ovarian screening trials
Recruitment start date
17/04/2001
Recruitment end date
29/09/2005
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University College London
London
W1T 7DN
United Kingdom
Trial participating centre
University College London
London
WC1E 6BT
United Kingdom
Trial participating centre
Belfast City Hospital
Belfast
BT9 7AB
United Kingdom
Trial participating centre
St Michael’s Hospital
Bristol
BS2 8EG
United Kingdom
Trial participating centre
University of Wales College of Medicine
Cardiff
CF14 4XN
United Kingdom
Trial participating centre
Derby City General Hospital
Derby
DE22 3NE
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Gateshead
NE9 6SX
United Kingdom
Trial participating centre
Liverpool Women’s Hospital
Liverpool
L8 7SS
United Kingdom
Trial participating centre
Royal Free Hospital
London
NW3 2QG
United Kingdom
Trial participating centre
St Bartholomew’s Hospital
London
EC1A 7BE
United Kingdom
Trial participating centre
Manchester Royal Infirmary
Manchester
M13 9WL
United Kingdom
Trial participating centre
James Cook University Hospital
Middlesbrough
TS4 3BW
United Kingdom
Trial participating centre
Llandudno General Hospital
Gwynedd
LL30 1LB
United Kingdom
Trial participating centre
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
St Mary’s Hospital
Portsmouth
W2 1NY
United Kingdom
Trial participating centre
Gynaecological Cancer Research Centre (Observational longitudinal follow up study only)
Department of Women’s Cancer
Institute of Women’s Health
University College London
Maple House
1st floor
149 Tottenham Court Road
London
W1T 7DN
United Kingdom
Sponsor information
Organisation
University College London (UK)
Sponsor details
Gower Street
London
WC1E 6BT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (UK)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Department of Health (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Eve Appeal (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Randomised controlled trial:
Publications addressing each of the outcomes.
Observational longitudinal follow up study:
1. Gold access publication in 2019
2. The results will be publicised through broadsheet/radio/TV/ women’s magazines/press interviews/ Youtube/facebook.
3. Lay summaries will be provided to ovarian cancer charities for their websites and newsletters
4. Clinical trial registries will be updated
5. Data will be presented at scientific meetings and conferences
7. Full report will be submitted to the HTA journal
Intention to publish date
31/12/2019
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
Core Trial Publications
2008 results in https://www.ncbi.nlm.nih.gov/pubmed/19008269
2009 results in https://www.ncbi.nlm.nih.gov/pubmed/19282241
2011 results in https://www.ncbi.nlm.nih.gov/pubmed/21362184
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25964255
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/26573079
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27353822
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/26707054
Within-trial analysis
2006 results in https://www.ncbi.nlm.nih.gov/pubmed/16827831
2011 results in https://www.ncbi.nlm.nih.gov/pubmed/21362184
2012 results in https://www.ncbi.nlm.nih.gov/pubmed/22911637
2013 results in https://www.ncbi.nlm.nih.gov/pubmed/22791597
2013 results in https://www.ncbi.nlm.nih.gov/pubmed/23456790
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/26095052
Secondary Studies
2007 results in https://www.ncbi.nlm.nih.gov/pubmed/17237735
2011 results in https://www.ncbi.nlm.nih.gov/pubmed/21147030
2011 results in https://www.ncbi.nlm.nih.gov/pubmed/22086897
2012 results in https://www.ncbi.nlm.nih.gov/pubmed/23084519
2012 results in https://www.ncbi.nlm.nih.gov/pubmed/22008610
2012 results in https://www.ncbi.nlm.nih.gov/pubmed/22199143
2012 results in https://www.ncbi.nlm.nih.gov/pubmed/22596242
2012 results in https://www.ncbi.nlm.nih.gov/pubmed/23169294
2013 results in https://www.ncbi.nlm.nih.gov/pubmed/23652307
2013 results in https://www.ncbi.nlm.nih.gov/pubmed/24129231
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/24122770
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/25067956
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/25290619
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/24589827
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/25252818
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/24879829
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25304359
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25290539
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/26035703
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25597499
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25316052
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25848938
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/24938522
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/26573598
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/26819954
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27829038
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27903971
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/26815306
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27091764
2017 results in https://www.ncbi.nlm.nih.gov/pubmed/28659136
2018 results in https://www.ncbi.nlm.nih.gov/pubmed/29587697
UKCTOCS Psychosocial study
2010 results in https://www.ncbi.nlm.nih.gov/pubmed/20648018
2014 results in https://www.ncbi.nlm.nih.gov/pubmed/24865441
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/26222482
Reproductive/lifestyle factors descriptive study:
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28264823
Complementary and alternative medicine/non-pharmacological interventions use for menopausal symptoms:
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28326899
The effect of ovarian cancer screening on sexual activity and functioning:
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28324886
Publication citations
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Results
Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A, Lewis S, Davies S, Philpott S, Lopes A, Godfrey K, Oram D, Herod J, Williamson K, Seif MW, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso NN, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Singh N, Dawnay A, Skates SJ, Parmar M, Jacobs I, Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)., Lancet Oncol., 2009, 10, 4, 327-340, doi: 10.1016/S1470-2045(09)70026-9.
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Results
Jacobs I, Gentry-Maharaj A, Burnell M, Manchanda R, Singh N, Sharma A, Ryan A, Seif MW, Amso NN, Turner G, Brunell C, Fletcher G, Rangar R, Ford K, Godfrey K, Lopes A, Oram D, Herod J, Williamson K, Scott I, Jenkins H, Mould T, Woolas R, Murdoch J, Dobbs S, Leeson S, Cruickshank D, Skates SJ, Fallowfield L, Parmar M, Campbell S, Menon U, Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort., Lancet Oncol., 2011, 12, 1, 38-48, doi: 10.1016/S1470-2045(10)70268-0.
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Results
Sharma A, Gentry-Maharaj A, Burnell M, Fourkala EO, Campbell S, Amso N, Seif MW, Ryan A, Parmar M, Jacobs I, Menon U, , Assessing the malignant potential of ovarian inclusion cysts in postmenopausal women within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a prospective cohort study., BJOG, 2012, 119, 2, 207-219, doi: 10.1111/j.1471-0528.2011.03038.x.
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Results
Gentry-Maharaj A, Taylor H, Kalsi J, Ryan A, Burnell M, Sharma A, Apostolidou S, Campbell S, Jacobs I, Menon U, Validity of self-reported hysterectomy: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)., BMJ Open, 2014, 4, 3, e004421, doi: 10.1136/bmjopen-2013-004421.
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Results
Sharma A, Beveridge HA, Fallowfield LJ, Jacobs IJ, Menon U, Postmenopausal women undergoing transvaginal ultrasound screening prefer not to have chaperones, BJOG, 2006, 113, 8, 954-957.
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Results
Menon U, Gentry-Maharaj A, Ryan A, Sharma A, Burnell M, Hallett R, Lewis S, Lopez A, Godfrey K, Oram D, Herod J, Williamson K, Seif M, Scott I, Mould T, Woolas R, Murdoch J, Dobbs S, Amso N, Leeson S, Cruickshank D, McGuire A, Campbell S, Fallowfield L, Skates S, Parmar M, Jacobs I, Recruitment to multicentre trials--lessons from UKCTOCS: descriptive study, BMJ, 2008, 337, a2079, doi: 10.1136/bmj.a2079.
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Results
Burnell M, Gentry-Maharaj A, Ryan A, Apostolidou S, Habib M, Kalsi J, Skates S, Parmar M, Seif MW, Amso NN, Godfrey K, Oram D, Herod J, Williamson K, Jenkins H, Mould T, Woolas R, Murdoch J, Dobbs S, Leeson S, Cruickshank D, Campbell S, Fallowfield L, Jacobs I, Menon U, Impact on mortality and cancer incidence rates of using random invitation from population registers for recruitment to trials, Trials, 2011, 12, 61, doi: 10.1186/1745-6215-12-61.
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Results
Sharma A, Apostolidou S, Burnell M, Campbell S, Habib M, Gentry-Maharaj A, Campbell S, Amso N, Seif MW, Fletcher G, Singh N, Benjamin E, Brunell C, Turner G, Rangar R, Godfrey K, Oram D, Herod J, Williamson K, Jenkins H, Mould T, Woolas R, Murdoch J, Dobbs S, Leeson S, Cruickshank D, Fourkala E-O, Ryan A, Parmar M, Jacobs I, Menon U, Risk of epithelial ovarian cancer in asymptomatic women with ultrasound-detected ovarian masses: a prospective cohort study within the UK collaborative trial of ovarian cancer screening (UKCTOCS), Ultrasound Obstet Gynecol, 2012, 40, 3, 338-344, doi: 10.1002/uog.12270.
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Results
Gentry-Maharaj A, Sharma A, Burnell M, Ryan A, Amso NN, Seif MW, Turner G, Brunell C, Fletcher G, Rangar R, Fallowfield L, Campbell S, Jacobs I, Menon U, Acceptance of transvaginal sonography by postmenopausal women participating in the United Kingdom Collaborative Trial of Ovarian Cancer Screening, Ultrasound Obstet Gynecol, 2013, 41, 1, 73-79, doi: 10.1002/uog.12262.
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Results
Sharma A, Burnell M, Gentry-Maharaj A, Campbell S, Amso NN, Seif MW, Fletcher G, Brunel C, Turner G, Rangar R, Ryan A, Jacobs I, Menon U; United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), Factors affecting visualization of postmenopausal ovaries: descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), Ultrasound Obstet Gynecol, 2013 , 42, 4, 472-477, doi: 10.1002/uog.12447.
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Results
Gentry-Maharaj A, Fourkala EO, Burnell M, Ryan A, Apostolidou S, Habib M, Sharma A, Parmar M, Jacobs I, Menon U, Concordance of National Cancer Registration with self-reported breast, bowel and lung cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening, Br J Cancer, 2013, 109, 11, 2875-2879, doi: 10.1038/bjc.2013.626.
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Results
Sharma A, Burnell M, Gentry-Maharaj A, Campbell S, Amso NN, Seif MW, Fletcher G, Brunell C, Turner G, Rangar R, Ryan A, Jacobs I, Menon U, Quality Assurance and its impact on ovarian visualisation rates in the multicentre United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), Ultrasound Obstet Gynecol, 2015 , doi: 10.1002/uog.14929.
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Results
Menon U, Ryan A, Kalsi J, Gentry-Maharaj A, Dawnay A, Habib M, Apostolidou S, Singh N, Benjamin E, Burnell M, Davies S, Sharma A, Gunu R, Godfrey K, Lopes A, Oram D, Herod J, Williamson K, Seif MW, Jenkins H, Mould T, Woolas R, Murdoch JB, Dobbs S, Amso NN, Leeson S, Cruickshank D, Scott I, Fallowfield L, Widschwendter M, Reynolds K, McGuire A, Campbell S, Parmar M, Skates SJ, Jacobs I, Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening, J Clin Oncol, 2015 , 33, 18, 2062-2071, doi: 10.1200/JCO.2014.59.4945.
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Results
Gentry-Maharaj A, Karpinskyj C, Glazer C, Burnell M, Ryan A, Fraser L, Lanceley A, Jacobs I, Hunter MS, Menon U, Use and perceived efficacy of complementary and alternative medicines after discontinuation of hormone therapy: a nested United Kingdom Collaborative Trial of Ovarian Cancer Screening cohort study, Menopause, 2015, 22, 4, 384-390, doi: 10.1097/GME.0000000000000330.