Multi-cancer earlier detection tests: implications for screening programmes

Identifying cancers at an earlier stage, when there are more treatment options, often leads to improved survival. Screening asymptomatic populations can be an effective way to detect cancers at an earlier stage, thereby improving outcomes. However, the benefits of screening must outweigh the potential harms.

The UK National Screening Committee (UK NSC) has recommended screening programmes for breast, bowel, and cervical cancers, which have been rolled out across the UK. Targeted lung screening was also recently recommended by the UK NSC and is currently being rolled out in England. The three established programmes save thousands of lives each year. At present, each of them is separate and utilises different technologies for testing.

The recent emergence of multi-cancer earlier detection tests (MCEDs) represents an exciting progression in screening test technology. They could lead to iterative improvements to the UK’s individual screening programmes, or they could change the entire cancer screening paradigm by making it possible to screen for multiple cancers at once. 

This is the second article in our multi-cancer test (MCT) explainer series. Last time, we took a closer look at what exactly MCTs and MCEDs are, what they could do for cancer screening, and how far they are from being ready for use in the NHS. Now, we’re investigating the specific ways MCEDs could be used as part of screening programmes and the key questions they raise. 

The potential for cancer screening offered by MCEDs

There are many different ways that MCEDs could contribute to cancer screening. We’re focusing on four of them in particular. 

1. One potential use of this technology is as a replacement test in current site-specific screening programmes. Many MCEDs are based on a blood draw. They have a potential advantage (if they perform well), as, in comparison to certain tests, such as mammography, they may be cheaper and easier to administer and more accessible to patients. That may also make them more acceptable to the public.

2. As we discussed in the previous article, no test is perfect, and there is always room for improvement. A second potential use of MCEDs is as an additional screening test within the current programmes, which can be combined with the existing test to give better information. For example, while mammography is a good screening test, it cannot differentiate between sub-types of breast cancer. It’s possible that MCEDs could be developed to be used alongside mammography to help differentiate different breast cancers and offer tailored management. 

3. A third potential use is as part of risk stratified screening, which is also being discussed as a mechanism to improve screening programmes. Risk stratified screening tailors the frequency of screening intervals and the types of screening tests offered to a person’s risk of developing cancer. Cancer risk can be calculated using different information, including medical history, lifestyle, socioeconomic status, and clinical indicators from other tests. Results of MCED analysis could potentially feed into this process and contribute to risk assessment.

4. Current screening programmes are for individual cancers, which means that many people require multiple appointments and tests for cancer screening. As such, perhaps the most transformative potential use for MCEDs is as part of a multi-cancer screening programme. MCEDs have the potential to be used to more efficiently screen for lots of different cancers at the same time, including those for which screening is not currently offered, such as rarer cancers.  

What’s needed to change screening programmes? 

Setting up and delivering a screening programme is far from a simple task. Decisions need to be made on who will be invited to participate and how the programme will run to make sure it helps reduce cancer mortality without disrupting the NHS’s ability to provide care elsewhere.  

Those decisions can’t be made without a very deep understanding of how a specific screening test functions, but that’s not the only important consideration. Screening programmes also need to consider how to identify people eligible for the test and implement a protocol for administering it, as well as clear pathways for any necessary follow-up tests or treatments. 

The current screening programmes are continuously monitored and can be modified. We have recently seen changes in the tests offered as part of the bowel cancer and cervical cancer screening programmes, for example. However, given the complexities of setting up and delivering screening, these changes were only made after careful consideration of the impact of any modification.   

The tests used in existing programmes can only be modified if there is evidence showing the new test performs as well as or better than the existing one. The practicality and usability of the different tests also need to be compared. In addition, as any MCED that might be suitable for screening is likely to be a blood test, the health system will also need to consider how this changes screening delivery pathways.   

Making modifications that might bring the current screening programmes together into a multi-cancer screening programme (i.e. by replacing the different tests with a single test) is more complex. The current screening programmes are offered to different groups of people (e.g., women between the ages of 50 and 70 are invited for breast screening, while people aged 54 to 74 are invited for bowel screening). If they are combined, determining how to make a feasible programme is an issue. There would also need to be sufficient evidence showing that the test works well across these population groups for these cancers.  

Further complexity arises when considering including cancers that the NHS doesn’t currently screen for in a multi-cancer screening programme. This would require the development of an entirely new screening programme that absorbs the elements of existing programmes (if it’s deemed the MCED is better than existing tests) and introduces additional elements for cancers that previously did not have a screening test.  

In this case, introducing a new multi-cancer screening programme utilising MCEDs would require close consideration of a range of factors, including:  

• who will be eligible for screening 
• which cancers should be included as part of the programme  
• how people who participate in screening are going to be managed
• how to deliver an equitable programme

Designing and evaluating multi-cancer screening programmes and MCEDs

There’s no precedent for screening for multiple cancers at once, and we still don’t know the best way to design this type of programme. There are several questions that need to be addressed within this design process, and experts from across a range of disciplines should be engaged to create a programme that can be successfully adopted by the health system and engaged with by the public.   

Questions to be addressed include:  

• how to absorb and limit disruption to successful existing programmes 
• how to design onward referral and diagnostic pathways, considering the fact that increased demand will create a need for extra capacity in diagnostic and treatment workforce, kit and estate 
• how to design public invitation and other engagement materials for this novel programme and test, given the potential for different levels of acceptability across demographic groups 

A crucial part of implementing any new test or programme is making sure it can be effectively evaluated. One of the special complexities of MCEDs comes from the fact that they might perform differently for different types of cancer. That means we also need to have a clear plan for assessing their diagnostic accuracy across each cancer site separately, as well as evaluating the cost-effectiveness, benefits and risks of the test overall. In practice, it may also mean that different safety netting mechanisms (which ensure timely reappraisal of a patient’s condition) will be needed across cancer sites. Different MCEDs are likely to perform differently, too, so each one needs to be evaluated independently to determine whether it should be used in a multi-cancer screening programme. To do this, we will need to build clear consensus around which parameters (such as test sensitivity and specificity) will be evaluated for each cancer site, how these thresholds will be applied to the test overall (including in cost-effectiveness analysis) and how we can get timely information on the benefits of using MCEDs as part of a screening programme. 

As such a screening programme would likely have a big impact on how the entire health system operates, another fundamental consideration is health economics. For example, a positive MCED test result could add costs by increasing the number of follow-up diagnostics required without an associated improvement in outcomes. For this reason, a full health economic assessment is vital to determine whether a new screening programme will be cost-effective as well improving patient outcomes. Health systems have a finite amount of money to spread across all programmes and services to drive improvements in patient outcomes, so any new screening programme must be designed to mitigate unintended consequences on the wider health system.  

Preparing for the future 

Findings from the ongoing NHS England Galleri trial should provide initial evidence the health service can use to start answering some of the key questions around the use of MCEDs. The study has recruited around 140,000 people aged 50 to 77 to test GRAIL’s Galleri multi-cancer blood test as a potential MCED screening test. It’s an early step towards understanding how well these tests function and where patients with a positive MCED result should be referred to, as well as the impact on onward diagnostic testing and care pathways, and patient behaviour. 

For all that the NHS-Galleri trial might teach us, there are many other companies developing MCEDs and we don’t yet know which one might be the most beneficial tool for a screening programme. It’s only the first in the series of studies we’ll need to inform how these tests can be used for cancer screening.  

With MCED trials already underway and innovation moving at a fast pace, health system leaders, the UK NSC, industry and the cancer research community need to begin discussing how to evaluate such trials (as we’ve laid out above) and plan for the adoption of these types of technologies. To this end it is encouraging to see that the UK NSC has set up a task group to review the evidence and formulate its position on the evaluation of MCEDs for screening. 

What’s next? 

Whatever happens in the early trials of MCEDs for cancer screening, it’s clear we’re at the beginning of a long journey. Even if, after fully evaluating all the benefits and risks, the UK decides to implement a MCED-based screening programme, we won’t have reached the end of that road. The technology that underpins MCEDs will evolve, and other innovations will also shape cancer screening, diagnosis and care, so the impact of a multi-cancer screening programme is likely to change over time. Continued horizon scanning, assessment and evaluation of the evidence will help us make sure we’re making the best decisions.