Published on 25 September 2023
Project Manager
Lynch Syndrome Optimal Pathways – Quality Improvement Project
By Grace Garner, Cheshire and Merseyside Cancer Alliance Project Manager
What is Lynch syndrome?
Lynch syndrome is an inherited genetic condition that causes people to have an increased risk of developing certain types of cancer.
There is a high risk of bowel cancer, with women having the additional high risk of gynaecological cancers including endometrial (womb) and ovarian cancer. There is also a small increase in the likelihood of developing a few other cancer types as shown in the diagram below.
Having Lynch syndrome does not mean a person will definitely go on to develop cancer, but it does mean they have an increased risk.
There are low-cost treatments and services available to help people with Lynch syndrome manage and reduce their risk of developing cancer. These include symptom awareness and regular surveillance appointments to support early detection, preventative medicines such as aspirin, lifestyle changes and options for surgery where appropriate.
In addition, people with Lynch syndrome have colorectal cancers that are more responsive to immunotherapy treatment options. This demonstrates the importance of the prompt timing of the initial tumour test which can inform treatment options.
What causes Lynch syndrome?
Lynch syndrome is caused by an alteration in one of five different genes: MLH1, MSH2, MSH6 and PMS2, which known as mismatch repair (MMR) genes, as well as the EPCAM gene. These genes normally help protect us from developing cancer by detecting and correcting errors that can occur during DNA replication.
If there is an alteration in one of these genes which prevents DNA repair, more errors build up in our DNA which can lead to abnormal growth and the development of cancer.
Project background
An estimated 175,000 people have Lynch syndrome in the UK but fewer than 5% of individuals know they have the condition (Bowel Cancer UK). Increasing the identification and diagnosis of Lynch syndrome is a top priority for NHS England (NHSE) as it is estimated that doing so could save over 300 lives annually in England.
The NHS Long Term Plan (LTP) is focussed on improving outcomes for cancer patients through earlier diagnosis with the ambition that by 2028 the proportion of cancers diagnosed at stage one and two will rise to three-quarters of cancer patients. For example, if all people with colorectal cancer and their family members were tested for Lynch syndrome and enrolled into appropriate surveillance pathways, in 2028 we would expect up to 380 more colorectal cancers to be diagnosed early. That equates to a 0.9%-point increase against the LTP ambition.
A simple initial screening test of the biopsy tumour tissue can be used to test for Lynch syndrome. This test looks for changes in the MMR genes and if abnormal, patients will have the option for genetic testing.
Since 2017, the National Institute for Health and Care Excellence (NICE) has recommended that all people with colorectal cancer are tested for Lynch syndrome using immunohistochemistry (IHC) or microsatellite instability (MSI) testing (DG27). In October 2020, NICE also recommended testing for Lynch syndrome in people who are diagnosed with endometrial cancer using immunohistochemistry (IHC) (DG42).
Despite this, pathways did not exist for pathology labs to undertake the volume of testing and compliance needed for all people eligible under the NICE guidelines across Cheshire and Merseyside, which was also reflected in the national picture.
Led by the NHSE and NHS Genomic Medicine Service Alliances (GMSA), a quality improvement project has been developed to ensure effective and fast diagnostic pathways are in place for colorectal and endometrial cancers nationally. The aims are to:
- Meet the NHS Long Term Plan ambition to diagnose cancer at an early stage.
- Increase the identification and diagnosis of Lynch syndrome.
- Improve cancer prevention through identification of individuals at risk through genetic cascade testing and support risk reduction.
- Implement stratified medicine to provide optimal treatment and surveillance services.
There was, therefore, an opportunity to align pathways and processes across Cheshire and Merseyside to drive standardisation, equity of access for testing and clinical benefit at a regional level.
Cheshire and Merseyside Cancer Alliance (CMCA) continues to work with the North West Genomic Medicine Service Alliance, Cheshire and Merseyside Pathology Network and clinical services to implement and sustain the optimal Lynch syndrome pathway for colorectal and endometrial tumour groups.
The project was split into two stages. Firstly, to ensure the initial tumour testing is carried out on biopsy samples reflexively (automatically without request) and secondly, to set up mainstreaming services within hospital trusts for genetic testing which would alleviate additional pressures on clinical genetics departments where resource is already stretched.
Cancer Alliance project – stage one
The regional preference across Cheshire and Merseyside pathology departments is for the initial tumour testing to be by IHC, a method of testing using antibodies to check for certain antigens (markers) in the tissue sample, which can be done within pathology laboratories. This negated the logistical issues and longer turnaround times of results for the alternate MSI testing to be carried out at regional genetics centres.
The top three barriers to implementing the Lynch syndrome optimal pathway were reported as:
- Lack of funding available for IHC tests
- Laboratory capacity at some sites
- Education in multidisciplinary teams (MDTs) for mainstreaming
Funding
NHSE funding was provided to each cancer alliance in England to facilitate this pathway and CMCA worked with key stakeholders to decide how best to spend this funding.
Whilst many options were considered, the majority of funding has been provided for initial tumour testing per capita diagnosed, based on diagnostic figures provided by pathology hubs. The remaining funding has been utilised as part of stage two in the optimal pathway for mainstreaming and sustainability.
The NHSE funding is transformational and, therefore, non-recurrent. It is the national
expectation that from April 2024, local commissioners within Integrated Care Boards (ICBs) will work with their providers to commission IHC reflex testing for all colorectal and endometrial cancers. CMCA is continuing to facilitate these conversations regarding sustainability and is supporting trusts as needed.
Capacity
Taking into account the capacity issues that some sites faced, the pathology model was re-designed slightly into testing ‘hubs’. The model included five main testing sites that the nine trust pathology laboratories divided into and was approved by key stakeholders.
Education
Working with secondary care trusts and the multidisciplinary teams (MDTs) for colorectal and endometrial cancers, a ‘Lynch champion’ has been appointed within each team. The champions are responsible for ensuring the initial tumour testing is carried out on each patient where appropriate and act as a safety net as pathways are being embedded. Detailed national education resources have been created for various workforce groups including primary care, histopathologists and those in MDTs. Teaching webinars have also been well received in our region which have been promoted to raise awareness, update on project progress and to provide educational resources and support.
Stage one of the optimal pathway is now successfully embedded across Cheshire and Merseyside. Reflex testing for all colorectal and endometrial cancers for Lynch syndrome is in place across the sub-region and pathways are working efficiently.
It has been difficult to quantify the success due to national testing figures running two years behind and, therefore, not reflecting current practice and acknowledging improvement. However, each trust was asked to complete an audit to provide to NHSE which reported an improvement in testing in Cheshire and Merseyside from a baseline of less than 20% compliance in November 2019, to above 90% compliance in December 2020.
Cancer Alliance project – stage two
If the initial tumour testing is suggestive of Lynch syndrome, this needs to be confirmed by a genetic or germline test which requires patient consent and a blood sample.
Currently, those patients whose tests suggest Lynch syndrome is present are referred to clinical genetics services to discuss their family history, consent and provide a blood sample for germline testing.
A truly mainstreamed clinical pathway, on the other hand, would mean the patient consent and blood sample would be taken in hospital trusts by the clinical team. Only those patients with a germline variant present (or those with discordant IHC and germline tests) would then be referred to clinical genetics services for further discussion, surveillance and cascade testing for family members, who also may test positive for this inherited condition.
If a parent has Lynch syndrome caused by a variant in one of the mismatch repair genes, each child has a 50% chance of inheriting Lynch syndrome. Therefore, identification of people with Lynch syndrome and their family members will offer cancer risk reducing options and support earlier diagnosis.
The mainstreaming pathway would be most beneficial to patients and more efficient overall. However, it is recognised that many clinicians are hesitant to undertake germline testing consent at present and there is a requirement for education and training to set up these clinics.
A proportion of the transformational funding for this work was contributed to a regional lead Lynch specialist nurse role. This person, now in post, is providing training to consultant and nursing colleagues across the region for them to confidently undertake germline consent and is supporting in the setting up of these local clinics.
This is likely to be completed this autumn across Cheshire and Merseyside, which is a great leap forwards in embedding the optimal pathway for colorectal and endometrial cancers.
The NW GMSA is also leading on the development of a regional expert centre which will support colleagues across the region on complex cases and hold regular MDT meetings to discuss and agree next steps for individuals.
CMCA also contributed a small amount of the funding to an MDT coordinator post as this will be vital for sustainability of the downstream pathway.
Surveillance
People diagnosed with Lynch syndrome will be registered to the Bowel Cancer Screening Programme and be offered a colonoscopy every two years.
The screening can be offered from the age of 25 or 35 until 75 years of age. If family members are also diagnosed with Lynch syndrome, they will be offered regular colonoscopies too.
This allows any growths (polyps) to be removed and cancer to be picked up early, when there is a good chance of successful treatment. If bowel cancer is diagnosed at the earliest stage, more than nine in ten people will be successfully treated.
The Cancer Alliance will continue learn from and share learning with colleagues across the country to support the sustainability of th
ese optimal pathways as they are embedded across our region.
Professor James Hill, deputy clinical lead for the North West Genomic Medicine Service Alliance, said: “Grace Garner and her colleagues in the Cheshire and Merseyside Cancer Alliance have done a great job in achieving the national target for compliance with the Lynch syndrome project.
“This will result in the effective and timely diagnosis of Lynch syndrome in patients with colorectal and endometrial cancer and greatly improve their care and the care of their families.”
Dr Zahed Khan, Consultant in Medical Oncology at The Clatterbridge Cancer Centre, said: “I am really happy that the test in relation to Lynch syndrome is now being done routinely for all patients diagnosed with colorectal cancer in our network.
“This allows us to identify those with Lynch syndrome and tailor their treatment approach, as well as appropriate genetic counselling extending to family members and targeted surveillance that will help diagnose other cancers, hopefully in early stage, leading to better overall outcomes.”
For more information on Lynch syndrome, see: