Lynch syndrome and endometrial cancer: How our research led to new NICE guidance

The publication of a new national health guideline on Lynch syndrome and endometrial (womb) cancer is an important step forward for women’s health, Lynch syndrome diagnosis, and cancer prevention. At The University of Manchester, I worked on the clinical research – led by my colleagues Professors Emma Crosbie and Gareth Evans – that built the medical evidence for this significant policy change. This is the story of how it came about.

The background

In 2015, we began calling for the automatic testing of women with womb cancer for a condition known as Lynch syndrome. Lynch syndrome is an inherited health condition that greatly increases an individual’s chances of developing womb, bowel, and other cancers.

In a series of videos for our #LetsTalkLynch campaign, where we partnered with Policy@Manchester and The Eve Appeal to spread awareness of this research, we argued that testing women with womb cancer for Lynch syndrome was important for a number of reasons:

• In women with Lynch syndrome, womb cancer often develops before bowel cancer – it is therefore potentially the first symptom a woman has Lynch syndrome. And so testing wombs cancers means we diagnose women with Lynch syndrome earlier. In turn, once diagnosed, these women can be enrolled in cancer risk reducing strategies such as colonoscopies (camera tests within the bowel), which greatly reduces their risk of dying from future cancers.
• Because Lynch syndrome is genetic, every diagnosis can lead to ‘cascade testing’ of family members, allowing more people to be diagnosed before they develop cancer. This empowers people to know about, and takes steps to manage, their own cancer risk

Our research showed that Lynch syndrome is as prevalent in womb cancer cases as it is in bowel cancer cases. In both, just over 3% of patients are likely to have Lynch. This is important because the body that sets national health guidance for England and Wales (NICE – the National Institute for Health and Care Excellence) had already published a guideline calling for Lynch syndrome testing for everyone diagnosed with bowel cancer.

Engaging with NICE

In 2018, we made contact with NICE and they agreed to a preliminary meeting. We explained our research had made clear the benefits of the universal testing for Lynch syndrome in womb cancer. The team at NICE warmly invite us to formally notify them of this evidence and advised us on the process with the aim of creating a new guideline.

We went through the early steps of engagement, preparing a Medical Technology Innovation Briefing (or, ‘Medtech’) laying out why it is important to conduct this testing, how the tests can be conducted, and the evidence on costings and acceptability (to patients) of testing. This MedTech was heavily informed by the research we had carried out at the University of Manchester. This briefing then led to NICE creating a committee tasked with scoping the topic and with developing a guideline.

The research team here did not take part in the committee’s work or guideline creation process, in order to ensure the neutrality and integrity of the process. In all, it took around 18 months, with a slight delay due to COVID-19 at the end.

Ultimately, the guideline (NICE Diagnostic Guidance 42) was published in the early hours of Wednesday, 28 October 2020.

The Guideline

The guideline follows the recommendations that led on from our research, that all women should be offered the Lynch syndrome test when they are diagnosed with womb cancer. By doing so, our research estimates that this guideline will enable:

• An additional 1,000 diagnoses of Lynch syndrome in England and Wales every year (that is, the total of womb cancer patients that test positive, plus the an average of three family members who test positive through ‘cascade testing’)
• Each of those individuals will hopefully receive risk-reduction advice, and enter into regular surveillance (such as colonoscopies) to pick up any future bowel cancer as quickly as possible. This is important as cancers found early are far more survivable.
• Each female family member who receives a Lynch syndrome diagnosis through a cascade test, will also have access to advice on life style, family planning and risk reducing surgery in the form of removal of the womb, tubes and ovaries at time best suited to the individual.

Given the genetic specificities of cancers, it is impossible to put a number on ‘lives saved’, but we know that, of that 1,000 additional people per year, many will go on to have their cancers detected sooner than would otherwise have been the case. With bowel cancer in particular, those early detections will massively increase the likelihood of surviving the disease. In addition, those who have risk reducing surgery will not go on to get womb cancer or ovarian cancer themselves.

We can also say that, with the advice and surveillance programmes that a Lynch syndrome diagnosis leads to, that those 1,000 people per year will find their life expectancy improved to the same level as someone without the condition.

All of this points towards a huge breakthrough in women’s health, cancer screening/detection, and survivability which can follow from the publication of this guideline.

The Future

This is, of course, not the end of the story. NICE guidelines are the ‘best practice’ standard that our health services should conform to, but they are neither mandatory or legally enforceable. The next step will be for us, as well as cancer charities, political leaders, and members of the public, to make the case to our healthcare commissioners (who pay for the services offered in hospitals) that this new NICE guideline should become standard practice.

One model for this next phase comes from the fantastic work of Bowel Cancer UK, who did not stop with the publication of NICE DG27 (Lynch syndrome testing in bowel cancer diagnoses) but have continued to drive the argument for adopting this guideline across the country. We hope that the publication of the guideline that our work has informed (DG42) will add new voices and new urgency to all existing calls for widespread Lynch syndrome testing as a matter of course.

Throughout this process, NICE have been open, engaging, and clearly dedicated to achieving the best outcomes, treatments, and quality of life for patients here in the UK. The process, although daunting at first, has shown the importance of regular and proactive contact between researchers, clinicians, and policymakers.

Our case is an example of how all of these groups, working together, have achieved something of genuine value for the individuals and families that we are here to help.

About the Author

Dr Neil Ryan worked with Professors Emma Crosbie and Gareth Evans as a doctoral researcher at The University of Manchester. As a result of his contribution to research on Lynch syndrome and endometrial cancer and his work on national policy engagement, Neil was awarded both the Faculty of Biology, Medicine and Health PGR Student of the Year award, and the University’s Distinguished Achievement Medal, in 2020. After his PhD research, Neil moved to Bristol where he works in gynaecology and obstetrics in the NHS.