Epidemiology and treatment outcomes of endometrial hyperplasia and cancer: A population-based investigation using routine administrative data

Endometrial cancer is the most commonly diagnosed gynaecological cancer and is the 4th most common cancer in UK women. Endometrial cancer rates have increased substantially; in the UK over 9,000 cases occur annually and rates have increased by over 50% over the past 20 years. Factors associated with prolonged oestrogen exposure are thought to be driving this including the dramatic increase in obesity rates and shifts in reproductive trends, e.g. delaying childbirth until later in life. There is no routine screening for endometrial cancer but endometrial hyperplasia, a recognised precursor, offers an opportunity for prevention, but little is known about its natural history and associated outcomes. Removal of the uterus (hysterectomy) is the primary treatment for endometrial cancer and some types of endometrial hyperplasia but there is a need to evaluate the long-term benefits and risks of fertility-sparing therapies, considering the alarming increases in endometrial cancer in premenopausal women.

This research will answer three primary research questions:
1. Which women are most at risk of progression from endometrial hyperplasia to cancer?
2. What is the impact of non-surgical, fertility-sparing therapies on future cancer risk and reproductive outcomes in endometrial hyperplasia patients?
3. What are the international trends in surgical and non-surgical treatments of endometrial cancer and how do these impact upon survival outcomes?

A pilot endometrial hyperplasia register, located within the Northern Ireland Cancer Registry (NICR), will be utilised and expanded upon to make it one of the world's largest endometrial hyperplasia registers. The register will be linked to NICR records to determine temporal trends in endometrial hyperplasia incidence and progression to endometrial cancer. Medical note reviews will provide details on patient and clinico-pathological factors while additional novel data linkages to drug dispensing and maternity records in Northern Ireland (NI) will be conducted to evaluate, for the first time, population patterns of low-cost progestogen therapies (delivered orally or, more recently via intrauterine devices) in endometrial hyperplasia patients and their long-term impact on clinical outcomes such as hysterectomy, live births and progression to cancer.

Using population-based linked data sources, accessed from established research links, European trends in the use of surgical and non-surgical treatments for endometrial cancer will be determined for the first time according to geography and healthcare systems. Pooled analyses of large endometrial cancer cohorts from the UK, Belgium and the Netherlands will be conducted to evaluate survival outcomes according to non-surgical, progestogen-based therapies. Future research will explore the development of patient decision aid tools to enable better informed joint treatment decision making. The involvement of patients and clinicians throughout will ensure that the research is clinically relevant.

This research programme will generate robust population-level evidence to inform diagnostic, treatment and surveillance strategies for women with endometrial hyperplasia and endometrial cancer and will ultimately lead to better informed clinical decision-making between women and their health care professionals.

The primary beneficiaries of this research include women diagnosed with endometrial cancer (or its precursor endometrial hyperplasia), clinicians, policy makers and healthcare providers.

Improved policy making:
In the short to medium-term, targeted dissemination of research findings to national and international clinical policymakers will be undertaken. By exploiting novel population-wide record linkages, this research will ascertain optimal surveillance and treatment strategies to enable the identification of women most at risk of malignant progression to endometrial cancer, where surveillance and treatment strategies can be better targeted. Evidence from population-representative studies are essential to inform clinical management guidelines so that women and their clinicians can make more tailored decisions regarding the risk-benefit profile of current surveillance and treatments options. The inclusion of European data sources means that the findings from research will likely inform international practice, as well as that within the UK.

Improved health systems:
The research findings will provide national healthcare providers with novel information on UK temporal trends in endometrial hyperplasia incidence on a population-level. This will allow for better informed medium to long-term planning of gynaecological health service needs in the UK (e.g. information systems, workforce, service delivery, technologies), therefore improving allocation of scare resources. The identification of women at low risk of progressing from endometrial hyperplasia to endometrial cancer will likely lead to a reduction in the number of hysterectomies performed in the UK and hence reduced morbidity and associated healthcare costs. In the longer-term, exploration of the development of decision support aids may result in improved communication between healthcare professionals and women with endometrial hyperplasia or cancer, as well as increased quality and efficiency of joint clinical decision making. Future economic beneficiaries will include potential commercial partners, for the development of (digital) treatment decision aids, which will be informed by the findings from the research programme.

Improved knowledge base:
Using secondary data sources, this research programme will generate population-representative evidence for the clinical management of common gynaecological conditions (endometrial cancer and its precursor condition endometrial hyperplasia) which will enable affected women and their health professionals to make better informed decisions regarding their care. For example, the Northern Ireland Hyperplasia Register will be expanded upon to become one of the largest registers of its kind in the world (first in UK) and will provide a unique resource to study the natural history and outcomes from this common condition. Regular stakeholder engagement throughout will ensure that knowledge is exchanged between relevant groups, e.g. patients, clinicians, policy makers, and will ensure that progress is monitored and evaluated throughout. Through our dissemination strategy, the wider UK female population will also benefit from this research through communication and engagement surrounding gynaecological cancer symptom awareness.

Improved capacity to produce and utilise research based on routine health records in order to improve of population health:
This research will increase capacity, in the short, medium and long-term, for population research in the UK that exploits routine health administrative data sources and will provide reliable resources (e.g. databases, IT, human resources) to develop and implement future research. Our dissemination and social media strategy will widely communicate the availability of resources within this fellowship. Moreover, my programme of research will especially raise the profile of gynaecological cancer research (and skills development) within the UK and further afield.