ISRCTN - ISRCTN22488978: UK Collaborative Trial of Ovarian Cancer Screening

Plain English Summary

http://cancerhelp.cancerresearchuk.org/trials/a-study-looking-at-screening-the-general-population-for-ovarian-cancer

Trial website

http://www.instituteforwomenshealth.ucl.ac.uk/womens-cancer/gcrc/ukctocs

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

http://www.instituteforwomenshealth.ucl.ac.uk/womens-cancer/gcrc/ukctocs/files/UKCTOCS_Patient_information_sheet.pdf

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

http://www.ucl.ac.uk/jro

Funders

Funder type

Research council

Funder name

Medical Research Council (UK)

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/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

Publication citations

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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text
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.
- PubMed Abstract
- Publisher Full Text

Additional files

Editorial Notes

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.