Title: Effectiveness and cost-effectiveness of gynaecological surveillance for women with Lynch syndrome: systematic reviews and economic evaluation
Funder: Department of Health and Social Care

Abstract: Background_x000D_ Around 1 in 300 people are born with genetic mutations (changes to the DNA in genes which stop them working properly) increasing their risk of developing cancer in their womb and ovaries (for women), as well as in their bowels (men and women). This is called Lynch syndrome (LS). Many women are unaware of this increased risk because of a historical lack of testing for LS, but recent NICE guidance means more women will soon be diagnosed._x000D_ Women diagnosed with LS are often offered surgery to remove the womb and ovaries. This is effective but is not always what women want and it may be unsuitable for women who have had previous surgery or have other health conditions. Surveillance (regular tests to see if a woman has signs of cancer) is an option for women who do not have this surgery. It could cost the NHS £500 per person per year. There are no guidelines on surveillance for womb and ovarian cancer from NICE or other key UK policy makers. As a result there is inconsistent NHS practice – not all women with LS are offered surveillance, which can be distressing as they may not have any other options to manage their risk. A recent meeting of experts including patients highlighted the need for more research on the benefits (effectiveness) and value for money (cost-effectiveness) of surveillance._x000D_ _x000D_ Aims_x000D_ To explore the effectiveness and cost-effectiveness of surveillance to manage and reduce the risk of womb and ovarian cancer for women with LS._x000D_ _x000D_ Methods_x000D_ We will bring together the results of all studies that have explored the effectiveness of surveillance to manage the risk of womb and ovarian cancer in LS and assess how reliable the results are – this is called a systematic review. We will also do a systematic review to find out how cancer, risk-reducing surgery and surveillance affect quality of life. We will estimate cost-effectiveness with a mathematical model, which will include longer term outcomes (such as cancer), quality of life and costs._x000D_ _x000D_ Patient and public involvement (PPI)_x000D_ Tracy Smith, who has LS and is a trustee of the charity Lynch Syndrome UK (LSUK), is part of the research team. She cannot have risk-reducing surgery due to complications of a previous bowel cancer and she has paid for surveillance in the past. Tracy has reviewed this proposal and worked with the LSUK Facebook group to bring their experiences. She will share her expertise and lived experience of LS and surveillance and share insights as a trustee of LSUK and a moderator of their Facebook group (>1900 members and 150 posts per month). She will be part of an advisory group with other experts._x000D_ We will run a workshop at the start of the project with an experienced PPI researcher to bring together women with LS, explain our plans and ask them how they think the research can be improved and how the results should be shared. We will also ask for two women from this workshop to join the advisory group with Tracy._x000D_ The advisory group will meet regularly during the project to make sure the patient voice is heard throughout._x000D_ _x000D_ Sharing the results_x000D_ We will explore how our work can inform guidelines on managing the risk of cancer in LS, identify key questions for research, present findings at the LSUK conference in 2021 (mainly attended by patients), create summaries to share through social media and with relevant organisations (e.g. LSUK, Eve Appeal), write papers for high-quality academic journals and present the work at scientific conferences.

Lay abstract: Research question_x000D_ What is the effectiveness and cost-effectiveness of surveillance for gynaecological cancer in women with Lynch syndrome?_x000D_ _x000D_ Background_x000D_ Lynch syndrome (LS) is a hereditary cancer syndrome which leads to significantly increased risk of colorectal, endometrial and ovarian cancer. To reduce the incidence and mortality of colorectal cancer for people diagnosed with LS, colorectal surveillance is recommended. A lack of comparable evidence has precluded recommendations for gynaecological surveillance. There is inconsistency across the NHS with only some providers offering surveillance. Surveillance includes a number of different technologies, e.g. hysteroscopy, endometrial biopsy, ultrasound and CA125 (a biomarker)._x000D_ _x000D_ Aims and objectives_x000D_ The primary aim is to determine the clinical effectiveness and cost-effectiveness of gynaecological cancer surveillance in women with LS, with secondary aims to investigate which women may benefit most and to identify if further primary research is needed._x000D_ The objectives are to conduct: systematic reviews of clinical and cost-effectiveness studies of gynaecological surveillance (Work Packages 1 and 2); a systematic review of preference-based utility values for relevant gynaecological health states (Work Package 3); an economic evaluation of gynaecological surveillance using an economic modelling approach (Work Package 4)._x000D_ _x000D_ Methods_x000D_ Systematic reviews (WP1-3): These will follow best practice for systematic reviews, including searching multiple bibliographic databases with strategies designed by an information specialist, two reviewers independently screening for eligibility, and assessing study quality using established tools. WP1 and WP2 will share searches and will focus on the population of women with LS. WP1 will consider the effectiveness of surveillance in improving outcomes (e.g. survival, mortality, fertility, cancer stage), the ability of surveillance to detect cancer and the harms associated with surveillance (pain and adverse events). WP2 will consider the cost-effectiveness of surveillance for women with LS. WP3 will estimate the impact of cancer, surveillance and risk-reducing surgery on health-related quality of life using preference-based measures._x000D_ Economic evaluation (WP4): A whole disease model for women with LS will be developed to estimate the cost-effectiveness of surveillance, characterise the uncertainty in cost-effectiveness, identify key factors affecting cost-effectiveness and estimate the value of future primary research. Lifetime costs and QALYs will be modelled for a variety of surveillance strategies and for alternatives, e.g. risk-reducing surgery._x000D_ _x000D_ Timelines for delivery_x000D_ The project will commence on 1 April 2020 and be completed in 18 months. WP1–3 are expected to be completed in the first 7 months (except an update for WP1 in April 2021) to support WP4._x000D_ _x000D_ Anticipated impact and dissemination_x000D_ If surveillance is shown to be effective and cost-effective then women currently unable to access it should be able to do so, lowering their risk of getting or dying from cancer. If surveillance is shown to be ineffective then it can be stopped, saving NHS resources. The research will also help to guide further research through a value of information analysis._x000D_ The results will be disseminated through open access journal publications, patient materials to be shared through social media and relevant organisations, and an open source release of the economic model.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS