Early removal of Fallopian tubes and delayed removal of ovaries in women at high risk of ovarian cancer

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-to-prevent-ovarian-cancer-by-removing-the-fallopian-tubes-and-then-the-ovaries-protector (added 10/03/2021)

Background and study aims
Some women have an inheritable fault in their genetic code which increases their risk of developing ovarian cancer. Genes in which a fault may lie are BRCA1/ BRCA2/ RAD51C/ RAD51D/ BRIP1. Some women with a strong family history of ovarian cancer or breast and ovarian cancer may also be at increased risk. There is currently no screening programme for ovarian cancer available on the NHS. Therefore current practice is to offer women at increased risk, once they have completed their family, an operation to remove their fallopian tubes and ovaries. This procedure is called risk-reducing salpingo-oophorectomy. This is the best known way to prevent ovarian cancer in women at increased risk. However, in women who are premenopausal it leads to early menopause. Early menopause has serious health implications. It results in menopausal type symptoms (e.g. hot flushes, changes in mood, reduced sex drive), increased risk of osteoporosis (brittle bones), heart disease, stroke, dementia and sexual problems. Research suggests many ovarian cancers start in the fallopian tube. This has led to the proposal of an alternative strategy to prevent ovarian cancer. This involves having the operation in two stages. The first operation involves removing the fallopian tubes alone. This is called 'early salpingectomy’. The second operation removes the ovaries after natural menopause (average age 51 in the UK). This is called 'delayed oophorectomy’. The advantage of this two-stage alternative is that it offers some protection against ovarian cancer in young women whilst avoiding negative health consequences of early menopause.
The aim of the PROTECTOR study is to assess the impact of this two-stage alternative approach on sexual function. The study also evaluates the impact on quality of life, hormonal well-being, psychological well-being and overall satisfaction. Outcomes from this new approach are compared to the traditional approach of removal of both tubes and ovaries at the same operation. We also compare this to the well-being of women who do not have an operation.

Who can participate?
Women at increased risk of developing ovarian cance, who are aged 30 years and over and have not gone through the menopause.

What does the study involve?
Participants will be given the choice of which arm of the study they wish to be part of:
1. RRESDO (risk-reducing early salpingectomy and delayed oophorectomy): the new, two-stage operation (initial removal of tubes alone, followed by later removal of ovaries at a second operation after natural menopause or sooner if requested).
2. RRSO (risk-reducing salpingo-oophorectomy): removal of both tubes and ovaries at the same time. This is the current standard operation offered on the NHS to prevent ovarian cancer.
3. Controls: no operation involved.
Everyone will be required to complete questionnaires at the start of the study and annually. These ask about medical history, family history, quality of life, sexual function, cancer worry, psychological well-being and how satisfied individuals are with their decision.
All participants will also have a blood test at the start of the study and during follow up for a hormone called FSH. This will provide information on how the ovaries are functioning. Women who decide to have an operation to prevent ovarian cancer (either RRSO or RRESDO) will have a baseline ultrasound scan to look at the ovaries and a blood test for an ovarian cancer marker called CA125.
A small number of women from each study arm will be approached to take part in an optional interview. Interviews will explore views on acceptability, interest, factors influencing decision-making and willingness to undergo the new two-stage operation. Those who go on to have an operation (RRESDO/RRSO), will be contacted 1 year after their operation for a follow-up interview to discuss their satisfaction with the process and their general health and wellbeing.

What are the possible benefits and risks of participating?
Benefits include:
1. The opportunity of having a two staged operation (RRESDO) to prevent ovarian cancer. This is not currently routinely available outside the study. It involves removal of the tubes in the first step followed by removal of ovaries at a later date.
2. Removal of the tubes alone will provide some protection against developing ovarian cancer and also preserve ovarian function which will delay or avoid early menopause. This can prevent the adverse health consequences of early menopause.
3. Participants will be given the choice of deciding which arm of the study they wish to be a part of: RRESDO (new procedure), RRSO (current standard practice), or controls (no surgery).
4. Participants will be contributing to research into preventing ovarian cancer in women at increased risk. Results of this study will help us better understand the impact of the new two stage procedure. This will help develop future clinical care guidelines and plan future care pathways for women at increased risk of ovarian cancer.
Risks:
1. Although there is evidence to suggest removal of tubes alone provides some protection against developing ovarian cancer, the precise extent of this protection is unclear. There is the possibility of getting ovarian cancer despite removal of tubes.
2. It is unclear if a possible benefit of reduced breast cancer risk is lost by not removing ovaries before menopause.
3. The two-stage option (RRESDO) involves two operations instead of one (RRSO: removal of both tubes and ovaries). Each operation has potential complications. As there are two operations this may lead to more complications overall.
4. There is concern that not everyone having their tubes removed initially will go on to have their ovaries removed at a later date. This would mean that these women who don’t do so could still remain at an increased risk of developing ovarian cancer.

Where is the study run from?
Queen Mary University of London (UK)

When is the study starting and how long is it expected to run for?
July 2018 to July 2028

Who is funding the study?
Barts and the London Charity

Who is the main contact?
1. Dr Ranjit Manchanda (scientific)
r.manchanda@qmul.ac.uk
2. Dr Faiza Gaba (public)
f.gaba@qmul.ac.uk

Contact information

Dr Ranjit Manchanda
Scientific

Barts Cancer Institute
Queen Mary University of London
Room 4
Basement
Old Anatomy Building
Charterhouse Square
London
EC1M 6BQ
United Kingdom

ORCID ID	0000-0003-3381-5057
Phone	+44 (0)7979 884575
Email	r.manchanda@qmul.ac.uk

Dr Faiza Gaba
Public

Barts Cancer Institute
ECMC
Queen Mary University of London
Charterhouse Square
London
EC1M 6BQ
United Kingdom

ORCID ID	0000-0003-4081-6883
Phone	+44 (0)20 7882 8491
Email	f.gaba@qmul.ac.uk

Study information

Eligibility

Locations

Countries of recruitment

• England
• Northern Ireland
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

Queen Mary University of London
University/education

Joint Research Management Office
5 Walden Street
London
E1 2EF
England
United Kingdom

Phone	+44 (0)20 7882 7260
Email	sponsorsrep@bartshealth.nhs.uk
Website	http://www.qmul.ac.uk/
"ROR"	https://ror.org/026zzn846

Funders

Funder type

Charity

Results and Publications

Study outputs

Additional files

ISRCTN25173360_PIS_v4_16Apr2018.pdf

Uploaded 02/04/2019

Editorial Notes

10/03/2021: Link to lay summary on CRUK added to the plain English summary.
11/09/2020: Publication reference added.
02/04/2019: The participant information sheet has been uploaded.