Early detection in hereditary cancers
Cost-effectiveness model of renal cell carcinoma (RCC) surveillance in hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome which leads to the development of cutaneous and uterine leiomyomata, and renal cell carcinoma (RCC). The risk of RCC is 21% in those with HLRCC by the age of 70 years, with the youngest reported diagnosis at age 11. Surgery is the mainstay for curative treatment of RCC, with a 75% five-year survival rate in patients diagnosed with early-stage disease. Where the disease has metastasised, immunotherapies and targeted therapies are the main treatment options.
HLRCC-associated RCC is very aggressive, with over 60% of symptomatic presentations being at stage three or four of the disease, where mean survival averages at 15.8 months. Thus, it is recommended in individuals with HLRCC who have not developed an RCC, that they receive annual surveillance by means of contrast-enhanced renal MRI (CERMRI).
It has been shown that RCCs detected through imaging surveillance, have all been stage one, which are all treatable through surgical intervention, with individuals alive and disease free at the time of censoring, ranging from 18 months to over 8 years.
We speak to Dr Emma Woodward, ACED Co-Director of Research. Emma undertook a study, with her health economics colleagues, investigating the cost-effectiveness of annual CERMRI surveillance of individuals of different ages with HLRCC versus a no surveillance strategy where symptomatic RCC is diagnosed through the NHS.
“I have a longstanding interest in hereditary cancer genetics. Right since the days of my PhD, I have tried to combine my research with my clinical work and see how we might do things better for individuals or families with or at risk of hereditary cancers.”
– Dr Emma Woodward, ACED Co-Director of Research
Annual renal imaging for members of the population with HLRCC has not previously been evaluated for cost-effectiveness. MRI surveillance for HLRCC is not always used, and as such, there is no current surveillance strategy for HLRCC-associated RCC within the NHS. At present, individuals are identified with symptoms through the healthcare system and undergo curative surgery.
In 2020, in collaboration with colleagues from London, Nottingham and Birmingham, Manchester researchers published the largest single clinical study of HLRCC to date. The findings from this cohort showed that the risk of developing RCC by 70 years of age was 21% and that if surveillance was undertaken, RCCs could be detected at an early stage (Stage 1) where outcomes are much better. For individuals diagnosed with Stage 3 or 4 disease, mean survival was just 15.8 months.
Benefits of determining cost effectiveness of renal screening
Knowing that annual renal MRI surveillance is clinically effective, the researchers then sought to evaluate the cost effectiveness of such a strategy in individuals with HLRCC who had not yet developed an RCC. Dr Emma Woodward teamed up with Dr Alex Thompson, a Health Economist from Manchester Centre for Health Economics (MCHE).
Together, the researchers developed a decision-analytic model which compared the costs and benefits of lifetime CERMRI surveillance versus no surveillance in HLRCC patients at different age starting points: 11, 18, 40 and 60 years. The benefits were measured in life-years gained (LYG), quality-adjusted life years (QALYs) and cost in GBP. This model used the real world data from the 2020 publication and was based on an NHS model of cost-effectiveness.
Outcomes provided by the model showed that RCC screening in patients with HLRCC was cost effective at all age groups modelled. The model showed that in the 40-year-old age group, the surveillance strategy was not only cost-effective, but in fact had a cost saving of £965 per patient. In addition, this age group saw an increase of 0.58 of quality-adjusted life years (QALYs) and an average of 0.3-1.52 life years gained (LYGs). Thus, carrying out this real-world economic analysis highlighted that it is beneficial to carry out lifelong screening of HLRCC patients in terms of cost to the NHS, life-years gained and quality of life for patients for all age groups modelled.
This research was funded by the NIHR Manchester BRC.
Importance for patient outcomes
HLRCC is rare, with older estimates suggesting an occurrence of 1 in 200,000 people while more recent estimates suggest a carrier frequency of 1 in 1,000. Because of its rare classification and low incidence, this hereditary condition has often slipped under the radar of institutions like NICE. With these findings, the benefits of renal imaging for HLRCC carriers are now in the public domain with clear evidence that it is worthwhile for both cost effectiveness and patient outcomes.
Due to the hereditary nature of this condition, it can affect a whole family across an entire spectrum of age groups, and so there’s a great importance to improve patient outcomes in this syndrome. This research is extremely important for people with HLRCC due to the high lifetime risk (21%) of developing RCC. Implementing of a surveillance strategy for people and families with HLRCC would significantly improve outcomes for patients, by picking up tumours at an earlier stage where they can be cured by surgery with a 75% five-year survival rate.
We are very lucky in the North West because we have such a willing patient population and without our patients, we couldn't do any of this work. We’ve got a really good partnership and they're keen for us to think about novel means of early detection.
Dr Emma Woodward
The next stage of this project is to continue thinking about what these results mean for the early detection of RCC. The team have started a pilot exploratory research project called the ELECTRIC study through the International Alliance for Cancer Early Detection (ACED) in collaboration with colleagues in Cambridge, UK and Stanford, USA.
In this pilot, HLRCC patients, together with patients with other hereditary renal cancer predisposition syndromes, who attend hospital each year for their annual imaging scan can also have blood taken for analysis of the platelet RNA signature. The idea behind this is that our platelets produce disease specific RNA signatures, and this can potentially be used as a biomarker for early RCC. Therefore, cohorts of patients with hereditary RCC predisposition undergoing surveillance provide the ideal study group for investigation of this potential early RCC biomarker.
It is hoped that this research will not only help families with hereditary RCC predisposition but provides a blueprint for other studies of novel means of detection in hereditary cancer predisposition families.
These early detection research studies are so important, and we are so fortunate to have such dedicated patients who are only too willing to contribute. The onus is on us to deliver!
Dr Emma Woodward