The long-term impact on deaths and cost-effectiveness of screening for ovarian cancer using a blood test and ultrasound

ISRCTN	ISRCTN22488978
DOI	https://doi.org/10.1186/ISRCTN22488978
ClinicalTrials.gov (NCT)	NCT00058032
Protocol serial number	Current Version 9.0
Sponsor	University College London (UK)
Funders	Medical Research Council (UK), Cancer Research UK, Department of Health (UK), The Eve Appeal (UK), Health Technology Assessment Programme

Submission date: 06/04/2000
Registration date: 06/04/2000
Last edited: 14/03/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-screening-the-general-population-for-ovarian-cancer

Contact information

Prof Usha Menon
Scientific

MRC Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
University College London
90 High Holborn, 2nd Floor
London
WC1V 6LJ
United Kingdom

ORCID ID	0000-0003-3708-1732
Phone	+44 (0)20 7670 4649
Email	u.menon@ucl.ac.uk

Prof Ian Jacobs
Scientific

Study contact for randomised controlled trial only
University of New South Wales
Sydney
NSW 2052
Australia

Phone	+61 (0)2 93851000
Email	i.jacobs@unsw.edu.au

Study information

Primary study design	Interventional
Study design	Part 1: Randomised controlled trial Part 2: Observational longitudinal follow up study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and the long-term impact of screening on ovarian cancer mortality in UKCTOCS
Study acronym	UKCTOCS and LTFU UKCTOCS
Study objectives	Current hypothesis as of 24/08/2020: 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. Previous 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(s)	North West Medical Research and Ethics Committee (renamed to North West – Haydock), 21/06/2000, ref: 00/8/034
Health condition(s) or problem(s) studied	Tubo-ovarian cancer
Intervention	Current intervention as of 24/08/2020: 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/ROCA 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) Participants will be followed up through national cancer and death registries and hospital administrative databases via data linkage using their NHS number and follow-up questionnaires. Quality of life questionnaires will be sent to women newly diagnosed with ovarian cancer. Previous 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 sent to women newly diagnosed with ovarian cancer
Intervention type	Other
Primary outcome measure(s)	Current primary outcome measure as of 24/08/2020: UKCTOCS: Ovarian cancer mortality at 7 years after randomisation. 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) up to 31st December 2014. Long term impact of screening on ovarian cancer mortality in UKCTOCS (LTFU UKCTOCS): 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) up to 30th June 2020. Previous primary outcome measure as of 04/01/2017: Randomised controlled trial: Ovarian cancer mortality at 7 years after randomisation. 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.
Key secondary outcome measure(s)	Current secondary outcome measures as of 24/08/2020: UKCTOCS: 1. Performance characteristics: Sensitivity, specificity, positive predictive values of the two screening strategies (multimodal and ultrasound) for detection of ovarian cancer diagnosed within 1 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. LTFU UKCTOCS: Cost-effectiveness of ovarian cancer screening: This will be assessed using individual patient datafrom 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 relevantPersonal Social Services Research Unit Cost exercise. Previous secondary outcome measures as of 04/01/2017: Randomised controlled trial: 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. 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. Previous secondary outcome measures as of 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
Completion date	31/12/2024

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	50 Years
Upper age limit	74 Years
Sex	Female
Target sample size at registration	200000
Total final enrolment	202638
Key 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
Key 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
Date of first enrolment	17/04/2001
Date of final enrolment	29/09/2005

Locations

Countries of recruitment

United Kingdom
England
Northern Ireland
Wales

Study participating centres

UKCTOCS Coordinating Centre - UCL (2001-2018

Gynaecological Cancer Research Centre
Department of Women's Cancer
Institute for Women's Health, UCL
London
W1T 7DN
United Kingdom

University College London - Tumour Marker Laboratory (2001-2012)

London
WC1E 6BT
United Kingdom

Belfast City Hospital

Belfast
BT9 7AB
United Kingdom

St Michael’s Hospital

Bristol
BS2 8EG
United Kingdom

University of Wales College of Medicine

Cardiff
CF14 4XN
United Kingdom

Derby City General Hospital

Derby
DE22 3NE
United Kingdom

Queen Elizabeth Hospital

Gateshead
NE9 6SX
United Kingdom

Liverpool Women’s Hospital

Liverpool
L8 7SS
United Kingdom

Royal Free Hospital

London
NW3 2QG
United Kingdom

St Bartholomew’s Hospital

London
EC1A 7BE
United Kingdom

Manchester Royal Infirmary

Manchester
M13 9WL
United Kingdom

James Cook University Hospital

Middlesbrough
TS4 3BW
United Kingdom

Llandudno General Hospital

Gwynedd
LL30 1LB
United Kingdom

Nottingham City Hospital

Nottingham
NG5 1PB
United Kingdom

St Mary’s Hospital

Portsmouth
W2 1NY
United Kingdom

UKCTOCS Coordinating Centre - MRC CTU at UCL (since 2018)

Institute of Clinical Trials & Methodology
University College London
London
WC1V 6LJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The individual participant data that underlie the results reported in The Lancet May 2021 article, after de-identification will be available upon request beginning 12 months after publication from the MRC CTU at UCL (mrcctu.datareleaserequest@ucl.ac.uk). Researchers will need to state the aims of any analyses and provide a methodologically sound proposal. Data requestors will need to sign a data access agreement, cover administrative costs and in keeping with patient consent for secondary use, obtain ethical approval for any new analyses.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2006		Yes	No
Results article	results	01/05/2007		Yes	No
Results article	results	13/11/2008		Yes	No
Results article	results	01/04/2009		Yes	No
Results article	results	10/08/2010		Yes	No
Results article	results	01/01/2011		Yes	No
Results article	results	01/03/2011		Yes	No
Results article	results	01/11/2011		Yes	No
Results article	results	01/01/2012		Yes	No
Results article	results	10/04/2012		Yes	No
Results article	results	05/06/2012		Yes	No
Results article	results	01/09/2012		Yes	No
Results article	results	01/11/2012		Yes	No
Results article	results	01/01/2013		Yes	No
Results article	results	15/01/2013		Yes	No
Results article	results	28/05/2013		Yes	No
Results article	results	01/10/2013		Yes	No
Results article	results	26/11/2013		Yes	No
Results article	results	03/03/2014		Yes	No
Results article	results	01/05/2014		Yes	No
Results article	results	30/05/2014		Yes	No
Results article	results	27/06/2014		Yes	No
Results article	results	01/08/2014		Yes	No
Results article	results	24/09/2014		Yes	No
Results article	results	01/12/2014		Yes	No
Results article	results	15/01/2015		Yes	No
Results article	results	01/02/2015		Yes	No
Results article	results	17/03/2015		Yes	No
Results article	results	01/04/2015		Yes	No
Results article	results	01/04/2015		Yes	No
Results article	results	20/06/2015		Yes	No
Results article	results	01/07/2015		Yes	No
Results article	results	01/07/2015		Yes	No
Results article	results	14/07/2015		Yes	No
Results article	results	01/10/2015		Yes	No
Results article	results	10/01/2016		Yes	No
Results article	results	01/02/2016		Yes	No
Results article	Key results discussing primary analysis	05/03/2016		Yes	No
Results article	results	01/04/2016		Yes	No
Results article	results	01/06/2016		Yes	No
Results article	results	15/06/2016		Yes	No
Results article	results	25/06/2016		Yes	No
Results article	results	09/11/2016		Yes	No
Results article	results	03/01/2017		Yes	No
Results article	results	06/03/2017		Yes	No
Results article	results	11/04/2017		Yes	No
Results article	results	01/06/2017		Yes	No
Results article	results	28/06/2017		Yes	No
Results article	results	27/03/2018		Yes	No
Results article	results	15/04/2020	16/04/2020	Yes	No
Results article	results	01/10/2019	22/07/2020	Yes	No
Results article	results	25/01/2021	27/01/2021	Yes	No
Results article	results on ultrasound strategy performance	18/02/2021	08/03/2021	Yes	No
Results article	Key long term follow up results	05/06/2021	13/08/2021	Yes	No
Results article	Exploratory analysis	01/09/2023	04/09/2023	Yes	No
Results article	Ovarian cancer symptoms in pre-clinical invasive epithelial ovarian cancer	17/11/2023	20/11/2023	Yes	No
Results article	Key primary and secondary outcome results	11/05/2023	14/03/2025	Yes	No
Other publications	update	01/03/2021	03/03/2021	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results				No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

14/03/2025: The following changes were made:
1. The study overall end date was changed from 31/12/2024 to 30/06/2020.
2. Publication reference added.
07/02/2025: Internal review.
20/11/2023: Publication reference added.
04/09/2023: Publication reference added.
13/08/2021: Internal review.
07/06/2021: IPD sharing statement added.
02/06/2021: Publication reference added and protocol/serial number updated from 7.1 to 9.0.
17/05/2021: PubMed address and total final enrolment added.
13/05/2021: Publication reference added.
08/03/2021: Publication reference added.
03/03/2021: Publication reference added.
27/01/2021: Publication reference added.
07/09/2020: The public title has been changed from "UK Collaborative Trial of Ovarian Cancer Screening" to "The long-term impact on deaths and cost-effectiveness of screening for ovarian cancer using a blood test and ultrasound".
24/08/2020: The following changes have been made:
1. The scientific title has been changed from "UK Collaborative Trial of Ovarian Cancer Screening" to "UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and the long-term impact of screening on ovarian cancer mortality in UKCTOCS".
2. The acronym has been changed from "UKCTOCS" to "UKCTOCS and LTFU UKCTOCS".
3. The study hypothesisis has been changed.
4. The ethics approval has been updated to reflect the new name for the ethics committee.
5. The trial setting has been changed from 'Hospitals' to 'Other'.
6. The condition has been changed from "Ovarian/tubal and primary peritoneal cancer" to "Tubo-ovarian cancer".
7. The intervention has been changed.
8. The primary outcome measure has been changed.
9. The secondary outcome measures have been changed.
10. The trial website has been updated.
11. The participant information sheet link has been updated.
12. The trial participating centre information for UCL has been updated.
13. The publication and dissemination plan has been changed.
14. The intention to publish date has been changed from 31/12/2019 to 31/01/2021.
15. The NIHR HTA programme has been added as a funder.
16. One of the scientific contact's details have been updated.
22/07/2020: Publication reference added.
16/04/2020: Publication reference added.
15/02/2019: Publication reference added.
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
15/02/2018: Publication references added.
23/03/2017: Publication references added.
10/01/2017: All publication references to date have been added.
04/01/2016: The trial record has undergone a significant update to incorporate a longitudinal follow up study. This involves additions to the study design, interventions and outcome measures fields. In addition, the outcome measures of the original study have been updated and the publication and dissemination plan and trial participating centre for the follow up study has been added (all other sites are for the original randomised controlled trial).
27/01/2016: Publication reference added.
01/10/2015: The following changes were made to the trial record:
1. The overall trial end date was changed from 03/11/2012 to 31/12/2024.
2. Cancer Research UK, Department of Health and The Eve Appeal were added to the list of funders.