Kidney cancer screening that’s targeted at people at higher risk shows promise and would be acceptable to the public.

Update June 16, 2021

This research briefing describes recent work at the University of Cambridge on kidney cancer screening, led by Dr Juliet Usher-Smith and Professor Grant Stewart.

Kidney cancer is the 7^th most common cancer in the UK and the incidence is projected to rise by 26% between 2014 and 2035, representing one of the fastest accelerating cancers within that timeframe. The disease is usually curable if identified early. A screening programme for kidney cancer might diagnose the disease at an earlier stage, reduce the prevalence of metastatic tumours at diagnosis, decrease the expenditure related to systemic therapies and improve survival.

The case for exploring the potential of a screening programme for this ‘silent’ cancer was first made over 15 years ago. Patients with renal cancer have lobbied for a kidney cancer screening study for many years and consider screening to be one of the major unmet research needs for this condition.

Since then, a growing body of evidence has been published. In 2020, Professor Stewart and Dr Usher-Smith, with colleagues, reviewed that literature against the criteria for screening set by the UK National Screening Committee, published in Nature Reviews Urology [¹]. They showed that kidney cancer meets many, but not yet all, of those criteria and that there remain several important questions to resolve before a large trial can be recommended. Those include establishing the best method for screening and the most appropriate target population, as well as the public acceptability and potential uptake of kidney cancer screening.

This is an area that patients and clinicians have been interested in for decades and now thanks to the funding from Kidney Cancer UK we have a clinical trial which will begin to allow us to answer if we should screen for kidney cancer – Professor Grant Stewart

In recent research, funded by Kidney Cancer UK, Dr Usher-Smith and Professor Stewart’s team at the University of Cambridge have explored public attitudes towards screening for kidney cancer and assessed whether targeted screening of higher risk individuals, called stratified screening, might be possible. They have also looked at what the public would think of a stratified screening programme and are now investigating the possibility of combining kidney cancer screening with lung cancer screening, through the Yorkshire Kidney Screening Trial (YKST).

Kidney Cancer UK CEO, Nick Turkentine, said; “We are proud to be supporting this important research and commend Dr Usher-Smith and Professor Stewart on their work to date. The positive thinking around a potential kidney cancer screening programme and the anticipation that people would attend if they were invited is very encouraging. We look forward to the Yorkshire Kidney Screening Trial to see the level of success the addition of a kidney scan to the lung scan brings.”

Key research findings

Taken together, this body of research shows:

• Kidney cancer meets many, but not yet all, of the criteria for screening set by the UK National Screening Committee;
• Most people think positively about potential kidney cancer screening and anticipate that they would attend if they were invited;
• Urine testing or low-dose computerised tomography (CT) scans combined with lung screening were the preferred test options;
• Several existing risk models are potentially useful in predicting who is more likely to get kidney cancer; and could be used to identify those at higher risk for targeted screening; and
• Using either genetics or risk models to determine eligibility for screening would be acceptable to most.

About the research findings

Most people think positively about potential kidney cancer screening and anticipate they would attend if they were invited.

For a screening programme to be successful, it must be acceptable to the general public and uptake must be high. The team explored attitudes to possible future kidney cancer screening, and to the different tests options that might be used in such a screening programme, through an online survey with 1,021 members of the public and published in BMC Urology [²]. They asked about their views on urine testing, blood testing, ultrasound, low-dose CT scans combined with lung screening and low- dose CT scans of kidneys alone.

Most participants would be ‘very likely’ or ‘likely’ to undergo each of the different screening tests – even though over 80% of people in the survey knew nothing about kidney cancer or had only heard of the condition before participating in the survey.

Urine testing or low-dose computerised tomography (CT) scans combined with lung screening were the preferred test options.

The choice of screening test had a big influence on potential uptake: over 90% of survey respondents said that they would accept an invitation for screening by urine testing, blood testing or low-dose CT combined with lung screening. Intention was lower for ultrasound (89.5%) and low-dose CT of kidneys alone (78.8%).

Analysis of free text responses made by 668 of the UK-based respondents to the survey, published in BMJ Open, [³] revealed that most individuals saw screening as a positive health behaviour and felt the benefits of early detection outweighed any burdens or harms. The lower acceptance of CT (of kidneys alone) and ultrasound was due to concerns about the radiation risks associated with a CT scan and the need to travel to a hospital for the test. Those who responded that they were unlikely to attend screening often cited general concerns about screening, including fear or worry about the results and unnecessary medical interventions. Notably, very few participants appeared to consider the reliability of the screening test, or their own risk of kidney cancer, when deciding whether they would be likely to attend screening.

These findings suggest that optimising the logistics of the screening programme and ensuring that the written information is comprehensive and uncomplicated, for example, around the radiation risk associated with CT scans, will be important. That information should also not be limited to the specific details of kidney cancer screening but should include an explanation of the rationale for screening in general and the potential benefits of early detection.

Several existing risk models are potentially useful in predicting who is more likely to get kidney cancer; and could be used to identify those at higher risk for targeted screening.

The low prevalence of kidney cancer in the general population means that screening everyone above a certain age may be inefficient. Stratification of the population into risk categories – identifying who is more or less likely to get kidney cancer using mathematical models, or risk models – may be the way forward. However, it was unclear if there were any existing risk models that could identify those at highest risk of developing kidney cancer.

In a systematic review of research published in European Urology Focus and led by Dr Hannah Harrison [⁴], the team found a number of risk models that are potentially useful in predicting who is at highest risk of developing kidney cancer. Some of the most promising models for a screening programme use information that could easily be obtained from medical records or self-assessment questionnaires, such as age, smoking status, and body mass index. One notable study also developed a high performing model by combining a blood-based biomarker (Kidney Injury Molecule-1) with age, sex and smoking status; however, this model has not been validated. The researchers are now using the UK Biobank cohort to compare the performance of the models and to estimate the potential public health benefits of using the risk models to determine who is eligible for screening compared to using age or sex alone. They have shown that the best performing models identify those at high risk better than age and sex alone, however, the improvement is small.

The success of any screening programme depends on people taking up the offer of screening. This funding has allowed us to show for the first time that kidney cancer screening is likely to be acceptable to most people and, despite not knowing much about kidney cancer, most would be likely to take it up – Dr Juliet Usher-Smith

Using either genetics or risk models to determine eligibility for screening would be acceptable to most people.

Before a risk-stratified screening programme can be shaped and developed, an essential step is to identify strategies that are acceptable to the public. Analysis of data from the online survey of 668 UK-based respondents, published in Health Expectations, showed that, although men are at higher risk of kidney cancer, using sex or a combination of age and sex, in which only men are invited or men are invited at a younger age than women, was less acceptable than using age alone [⁵]. Up to half of women and a third of men were also not comfortable with using sex alone to determine eligibility for screening.

However, using a genetic risk model, or a complex risk score based on age, sex, BMI, smoking, family history and lifestyle to determine eligibility for screening, is as acceptable as using age alone for both men and women.

Over 70% of participants were comfortable waiting until they were older if the complex risk score or genetics indicated they were low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. This suggests that using estimated risk, from risk models incorporating either lifestyle or genetic risk factors to determine who is eligible for kidney cancer screening, would be acceptable to the majority of individuals and may lead to higher uptake than a programme based only on age.

Next steps

The Yorkshire Kidney Screening Trial

Professor Stewart and Dr Usher-Smith are now investigating the feasibility of combining kidney cancer screening with lung cancer screening. In the Yorkshire Kidney Screening Trial (YKST), people taking part in a pioneering lung screening trial in Leeds (Leeds Lung Health Check) will also be offered screening for kidney cancer, thanks to additional funding from Yorkshire Cancer Research.

This study, led by the team at the University of Cambridge, is the first in the world to assess the feasibility and acceptability of adding kidney cancer screening to lung cancer screening and, if successful, will provide the data to inform a large trial of kidney cancer screening alongside lung cancer screening in the future.

This could be the most important 10-15 second CT scan of someone’s life as well as a key step in the development of kidney cancer screening – Nick Turkentine, CEO, Kidney Cancer UK

Patients who consent will have an extra kidney CT scan immediately following the CT scan of their lungs; this will add 10-15 seconds to the procedure. Clinicians caught Andrew MacNamara’s early stage kidney cancer during his lung scan. He told his story to Yorkshire Cancer Research, saying: “I was lucky that the doctors noticed something out of the ordinary on my lung scan, as they caught the top of the kidney, but I then needed to have a separate scan at hospital to fully check my kidneys. If they can scan the whole of the kidneys with the lungs at the same time that will be fantastic.”

The trial is delivered in partnership with Leeds Teaching Hospitals NHS Trust, the University of Leeds and Leeds City Council.

Dr Juliet Usher-Smith is a University Lecturer in General Practice at the University of Cambridge’s Primary Care Unit and Professor Grant Stewart is Professor of Surgical Oncology at the University of Cambridge and co-leads the Cambridge Urological Malignancies Programme.

Resources

CRUK Urological Malignancies Programme

Kidney Cancer UK

National Screening Committee

University of Cambridge Primary Care Unit

Yorkshire Kidney Screening Trial

References

1 Current evidence on screening for renal cancer. Juliet Usher-Smith, Rebecca K. Simmons, Sabrina H. Rossi, Grant D. Stewart. August 2020. Nature Reviews Urology.

2 Public attitudes towards screening for kidney cancer: an online survey. Laragh L. W. Harvey-Kelly, Hannah Harrison, Sabrina H. Rossi, Simon J. Griffin, Grant D. Stewart, Juliet A. Usher-Smith. October 2020. BMC Urology.

3 Reasons for intending to accept or decline kidney cancer screening: thematic analysis of free text from an online survey. Charlotte Freer-Smith, Laragh L.W. Harvey-Kelly, Katie Mills, Hannah Harrison, Sabrina H. Rossi, Simon J. Griffin, Grant D. Stewart, Juliet A. Usher-Smith. May 2021. BMJ Open.

4 Risk Prediction Models for Kidney Cancer: A Systematic Review. Hannah Harrison, Rachel E. Thompson, Zhiyuan Lin, Sabrina H. Rossi, Grant D. Stewart, Simon J. Griffin, Juliet A. Usher-Smith. July 2020. European Urology Focus.

5 Acceptability and potential impact on uptake of using different risk stratification approaches to determine eligibility for screening: A population-based survey. Juliet A. Usher-Smith, Laragh L. W. Harvey-Kelly, Sabrina H. Rossi, Hannah Harrison, Simon J. Griffin, Grant D. Stewart. Dec 2020. Health Expectations.