Liquid biopsies: towards faster cancer treatment

The rise of precision medicine and targeted cancer treatments

Surgery has long been and continues to be the main first-line treatment for cancers that can be surgically removed. It’s often followed by other established treatments like chemotherapy and radiotherapy, which are used to kill any remaining cancer cells and stop the cancer coming back. In other cases, when surgery isn’t suitable, or a cancer has grown and spread too far to be cut out, doctors might start with chemotherapy or radiotherapy instead. However, those may not always be the most effective options.

Liquid biopsies could help enable more people to access a newer approach to cancer treatment called precision medicine. 

Precision medicine is transforming cancer care by making it possible to tailor therapies to the specific genetic changes that are driving individual cancers to grow and spread. It relies on genomic testing, which allows healthcare teams to see whether a cancer has ‘actionable’ genetic changes. If those changes are present, oncologists can match patients to the corresponding targeted drugs, which are more likely to be successful than standard treatment. 

Genomic testing typically requires a tissue sample (biopsy) from a person’s tumour. But, as it’s not always possible to carry out those procedures, and they can take a long time to return results, liquid biopsies could offer a promising alternative. Easy to obtain liquid samples, such as blood, could be tested instead of solid tumours to identify actionable genetic changes. 

Let’s take a look at how that works and what it could mean.

How could liquid biopsies improve treatment decision making?  

The main advantages of liquid biopsy tests come from the fact they’re fast and non-invasive. 

Many liquid biopsies are designed to detect DNA that tumours shed into the blood. By finding and analysing this circulating tumour DNA (ctDNA), they can uncover the genetic changes that may be driving the growth of the tumour. In effect, they help doctors see what’s going on inside a tumour, and work out how to treat it, from a distance. 

By contrast, depending on the tumour’s location, a normal tissue biopsy might require invasive surgery. That’s much more complicated and uncomfortable. Tissue biopsies may have to be booked in busy operating room schedules, carried out by surgical teams and then assessed to ensure the sample is of a high enough quality for genomic testing. In some cases, they may also need to be repeated.  

In addition, some people may not be able to have these procedures (if, for example, their tumour is hard to access, or they’re too ill for surgery). Without liquid biopsy options, they would have to rely on standard treatments, even when they could qualify for a targeted therapy that may improve outcomes. 

Turnaround times for liquid biopsy samples are also generally faster than they are for traditional tissue biopsies. This is partly due to the ease of sample collection, but the process for sample handling and processing is also much more streamlined. That means liquid biopsy tests can help patients move from diagnosis to treatment more quickly. This can be critical, especially for those with late-stage cancers whose health may decline rapidly.

What are the limitations of using liquid biopsies to guide cancer treatment? 

Research has already shown that liquid samples can provide comparable levels of genetic information to solid tumour biopsies, but they aren’t suitable for every situation. Like all precision medicine tools, they need to be carefully matched to each patient’s specific circumstances.  

In particular, the way liquid biopsies work can make them unsuitable for some tumour types. For example, ctDNA-based liquid biopsy tests can only detect ctDNA in the blood once it reaches a certain level, but not all cancers shed lots of DNA and particularly not in their earlier stages. Even in advanced cancers, ctDNA levels can vary, sometimes leading to scenarios where a test fails to identify an important genetic alteration.  

For those reasons, it’s important to focus on when and where it’s most appropriate to use liquid biopsies.  

The more we can understand about the strengths and weaknesses of different biopsy options, the more we can do to meet the goals laid out in the UK’s genomics strategies. Although there are variations in progress, all four nations have prioritised promoting equitable access to genomic testing and targeted therapies, with clinically meaningful turnaround times. Liquid biopsies are applicable to each area, but implementation is complex, and tissue biopsies will continue to play a vital role in clinical care. Research is only becoming more important as we move away from a one size fits all approach to cancer treatment.  

Where could liquid biopsies make the biggest difference? 

Certain criteria can make liquid biopsies a particularly valuable alternative to traditional tissue biopsies. These include: 

• Tumour types that are often diagnosed at a late stage and/or experience delays to diagnosis. 
• Rapidly progressing cancers requiring swift intervention. 
• Cases where non-invasive options are essential, such as in older patients, children and young people, and those with inaccessible tumours or cancer of unknown primary (CUP), when there is evidence of cancer spread but doctors can’t tell where it started. 

There is lots of ongoing research across various cancer sites which meet some of these criteria.  

Lung cancer is one particularly active (and promising) research area. Many lung cancer patients are diagnosed at later stages, when prognosis is poorer, so reducing the time to treatment is critical. Genomic testing using tissue samples doesn’t work for all lung cancer patients, and some need multiple invasive and time-consuming biopsies before doctors can find the information they need. Offering genomic testing using liquid biopsies could help address some of these issues, increasing access to timely genomic testing so lung cancer patients can begin targeted therapies sooner.

Current UK liquid biopsy pilots and initiatives 

In England and Wales, two key pilot projects are exploring how liquid biopsies might fit into lung cancer care pathways: 

• The NHS England ctDNA Lung Implementation Pilot 
• QuicDNA study 

Both aim to see whether genomic testing using ctDNA-based liquid biopsies can reduce time to treatment and increase the number of people receiving targeted therapies compared to standard care. The pilots are also assessing economic implications and whether ctDNA-based liquid biopsy tests will improve outcomes for cancer patients.

There are also other initiatives working to accelerate and expand the adoption of ctDNA-based tests. The Circulating Tumour Biomarker Testing NHS Genomic Network of Excellence, for example, is using evidence gathered from existing projects, such as the lung pilots, to help expand liquid biopsy testing into the pathways of other cancer types.

There’s also the Stratified Medicine Paediatrics (SMPaeds) programme for children and young people with blood cancers and solid tumours, which is co-funded by Cancer Research UK.  

In SMPaeds1, the research team developed and validated a liquid biopsy to help find targeted therapies for children and young people whose cancers relapse after initial treatment. The new tool can offer more clinical information less invasively and in less time, meaning that it could be used repeatedly to track how cancers respond to treatment, or even remove the need for solid tumour biopsies entirely. SMPaeds2 is now investigating how oncologists can use the two types of biopsy together. 

While the liquid biopsy landscape in the UK is both exciting and promising, there are key barriers to overcome and important steps we need to take to successfully implement them.  

What’s needed for implementation? 

As well as gathering evidence to support use of liquid biopsies in cancer treatment pathways, we also need to consider the wider practicalities and complexities of adopting the technology. There needs to be a clear focus on: 

• developing and implementing guidelines to help clinical teams identify eligible patients early in their treatment journey 
• setting up efficient systems for collecting, transporting, and tracking blood samples to cope with high patient volumes  
• integrating liquid biopsy results directly into patient records to help ensure consistent, high-quality care 
• training healthcare professionals to interpret liquid biopsy genomic results and offering support to help them understand and act on more complex results 
• information governance and data protection
• ensuring equitable access to liquid biopsy testing across all four UK nations

If you’re interested in finding out more, this recent report on the lung pilots offers a detailed overview of some of the important considerations for integrating liquid biopsies into routine care. 

Looking forward with liquid biopsies  

The goal for the use of liquid biopsies in treatment selection is to improve outcomes by getting more patients on the right treatment in a timely manner.  

The potential is clear, but now researchers need to fully investigate the difference liquid biopsies can make in practice. It’s also vital to identify the people who could benefit most from liquid biopsies and ensure the infrastructure is in place to smoothly integrate them into clinical care. At Cancer Research UK, we’re continuing to monitor the evidence as it emerges and advocate for the changes needed for this technology to be adopted in the future.