What Could Liquid Biopsy Do for Oncology in the UK and What Is Needed to Realise Its Potential?

Cancer is a major global health burden causing
10 million deaths in 2020
. In the UK, there are nearly
375,000 new cancer cases per year
,
almost half caught only at later stages
, and only a 50 percent 10-year survival rate. The ability
to detect and diagnose cancer earlier
and better is a central part of
policy efforts
to tackle this disease and to improve patient prognosis and outcomes.
Blood tests offer hope with better and quicker cancer diagnosis, in the form of liquid biopsy. A
liquid biopsy is a test
conducted on a blood sample to search for live cancer cells or pieces of DNA from circulating (dead) tumour cells (ctDNA) or to look for tumour DNA in cell free DNA (
cfDNA
, released from cells in the body).
Diagnosing cancer through blood samples in this way could improve access to cancer testing in primary care settings and aid
earlier cancer detection and diagnosis
, including potentially in asymptomatic and at-risk groups. That could enable quicker referrals for staging and grading cancers and thus
timely access to treatments
. Blood samples could also potentially be collected more often than tumour biopsies can be carried out, and could also
be more acceptable for patients and improve their experience
.
In theory, blood-based tests could thus help with tackling bottlenecks for hospital scans. However, if more people are diagnosed through liquid biopsy and if these tests do not replace imaging but help triage or complement it, there could be an increase in demand for imaging to follow up.
Blood-based tests may enable pan-cancer diagnostics, which can potentially detect multiple cancers based on a single blood sample.
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Blood-based tests may also enable pan-cancer diagnostics, which can potentially detect multiple cancers based on a single blood sample. These have had some
promising clinical trial results
, and prompted growing interest in testing
wider-scale adoption in health
systems
. Other technologies in development can capture live circulating tumour cells (CTCs). CTCs allow additional analysis of cancers because replication of cells is used to understand mutations and metastasis mechanisms, new and novel therapy design, and therapy testing. Liquid biopsy is also being considered for ongoing follow-up monitoring, such as testing for the presence of cancer after chemotherapy or surgery.
What needs to be done to prepare health systems for routine use of liquid biopsy?
The possibilities are exciting, but for liquid biopsy to be routinely used in the UK National Health System (NHS), four key challenges will need to be addressed.
First, there are still issues to overcome related to test accuracy and when testing is appropriate, balancing test utility versus risk of errors or overtreatment
. There are
trade-offs to contend with
between diagnostic sensitivity (how likely it is that a test will produce a positive result in the case of a cancer) and diagnostic specificity (likelihood of wrongly identifying a cancer when it is not present). Even a small percentage of false positives or false negatives can put pressure on services. Aside from causing undue anxiety for patients, false positives can increase referral waiting times for all patients and could result in unnecessary, invasive, and costly follow-up procedures, which need to be balanced against the benefits of quicker tests for others. Although liquid biopsy tests may enable earlier detection, unless treatment appropriateness can be tailored in a personalised way to cancer type, stage, and need of specific treatment, there can be risks of
overtreating or subjecting patients to unnecessary side effects
.
Second, routine use of these tests requires appropriate infrastructure to be in place, from testing laboratories to wider health systems capacity for liquid biopsy
. The United Kingdom has
genomic testing laboratories
, but these facilities can be located far away from services where samples are taken from patients. As ctDNA has a short shelf-life, timely sample processing is key. Transport times and storage logistics can
create challenges
in their own right. There are some efforts, such as by
Royal Marsden NHS Foundation Trust
, to bring specialised liquid biopsy testing facilities that are usually located offsite to NHS sites so that samples can be processed in the hospital setting. In addition, while the
Genomic Laboratory Hubs
and
Genomic Medicine Service
alliances are building platforms and assay panels for testing for multiple cancer markers,
there are constraints in their capacity
—both in terms of staff and facilities—to deal with possibly significant increases in demand for testing with liquid biopsies for cancer.
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Third, the NHS and diagnostic labs must have enough appropriately trained and skilled staff, supported with clear guidance and quality control processes.
A skilled workforce
will be needed to collect, prepare, store, and process blood samples, as well as to analyse results, especially lab scientists and bioinformaticians.
Appropriate quality control
is also essential in test preparation, test conduct, and analysis. Evidence-based, expert-vetted
guidelines
for collecting, processing, keeping, and quality-assuring blood biospecimens for clinical assays have been developed in the United States by the National Cancer Institute Biospecimen Evidence-Based Practices and in Europe through the European Liquid Biopsy Society, with limited similar efforts in the United Kingdom.
Extra skills and capacity might be required to appropriately interpret the results of tests (including multi-analyte tests). This could mean specialised groups of medical experts
('molecular tumour boards')
that can apply molecular analysis to evaluate a single patient's hard-to-treat cancer, aiming to tailor that person's clinical and care pathway and help to give them the right targeted treatment. Clear guidelines and training for health care hospital staff like pathologists, nurses, and oncologists on
how liquid biopsy testing would fit into the clinical workflows
would also be needed, if these technologies are to be embedded into the NHS at scale. Primary care health professionals involved with screening people at risk and making onward referrals would also need to understand the overall patient care pathway and workflows.
Fourth, decisionmakers need to see evidence of real-world cost effectiveness.
Although there are some promising insights from clinical trials, real-world evidence on the cost effectiveness of liquid biopsy tests for use in oncology is still limited.
Based on
trial data
, some tests demonstrate promising results for identification of early-stage cancers. They range in sensitivity at stage 1 cancer at 16.8–99 percent, at stage 2 at 40.4–97 percent, at stage 3 at 62–99 percent, and at stage 4 at 57–98 percent. Trial data also show tests range in specificity at 58–>99 percent. In addition, a recent
systematic literature review
on the health economic evidence for liquid biopsy assays in cancer found that liquid biopsy was found to be cost effective in 75 percent of studies.
Although there are some promising insights from clinical trials, real-world evidence on the cost effectiveness of liquid biopsy tests for use in oncology is still limited.
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Evidence
suggests that, in comparison with standard-of-care or no-screening scenarios, liquid biopsy is cost effective in screening and early detection of gastric, colorectal, brain, and breast cancers, and as an approach to treatment selection for lung cancer. However, there are methodological issues in the current literature with many studies not reporting on any of the modelling challenges they may have faced. For instance, there could be challenges related to uncertainty or considering economic evaluation of tests in combination with treatments and challenges. Policymakers will need to see health economic analysis of test performance not only in trial environments, but also in real-world implementation contexts and test impacts on patient outcomes, clinical care pathways, and health service utilisation. Further research is also needed to better understand
whether some cancer types are more likely to benefit
from liquid biopsy tests than others.
There are efforts in the United Kingdom to improve the evidence base on
real-world implementation
success factors, such as patient and clinician acceptability, uptake, experience, and impact on health service delivery. Learning from NHS pilots will be key to decisions about wider scale roll-out of these innovative technologies. It will be important to ensure patients and clinicians are well informed about the potential and opportunities, but challenges and limitations associated with liquid biopsy tests are also part of the conversation about the future of using liquid biopsies in tackling the United Kingdom's cancer burden.
Overall, liquid biopsy for cancer has the potential to provide better and quicker testing for cancer, helping to improve diagnosis and treatment and improving cancer outcomes overall. As potential useful tests emerge, now is the time to consider what is needed to put them into everyday practice across the NHS. Addressing the four key issues of appropriateness, infrastructure, skills, and cost effectiveness will lay the foundations for making best use of these tests to address the challenge of cancer overall.
Mark L Cabling is an analyst in the Health and Well-Being research team at RAND Europe. Sonja Marjanovic is director of the health care innovation, industry, and policy portfolio at RAND Europe. The authors thank Nick Fahy for his helpful advice.
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