Nov ’25 – The rollout of ctDNA testing: what this means for patients and healthcare professionals
In this blog, consultant medical oncologist Dr Matthew Krebs, clinical lead for cancer genomics in the North West of England, explains the impact of recent changes to lung cancer testing in England.
Following a successful pilot, NHS England has made circulating tumour DNA (ctDNA) testing available for all eligible patients who have a suspected diagnosis of advanced non-small cell lung cancer (NSCLC).
This change promises to significantly reduce the wait time for genetic testing results, allowing tailored treatments to be introduced more quickly for patients.
In this blog, Matthew explains what this change means and the effect it will have on patients and healthcare professionals.
What is ctDNA testing and how does it work?
Circulating tumour DNA (ctDNA) testing, sometimes known as a ‘liquid biopsy,’ is a method of detecting fragments of cancer DNA which are released from tumours into a person’s bloodstream. In ctDNA testing, a simple blood sample can be analysed for these pieces of DNA.
Advanced sequencing technology is then used to look for genetic alterations in the DNA, including ALK rearrangements, which drive growth in specific cancers.
If these features are identified, a patient can be prescribed targeted therapies which are far more effective in treating specific cancers than more standard treatments.
What are the advantages of ctDNA testing?
The most significant advantage of ctDNA is its speed. Following a simple, non-invasive blood test, results can be delivered within two weeks – much more quickly than genomic testing from tissue which takes three to four weeks.
This gives the multi-disciplinary team (MDT) all the information they need to make decisions about treatment ina a quicker time frame.
What do the changes mean in practice?
Until now, a treatment plan for a patient with lung cancer has relied solely on a tissue biopsy. When lung cancer is suspected, doctors take a small sample of the tumour. Part of this sample goes to the histopathology lab, where pathologists confirm whether cancer is present and identify the type. Another part is sent to the regional genomics hub, where molecular testing is carried out to look for specific genetic alterations, such as ALK rearrangements, that can guide treatment decisions.
From May 2025, following a successful pilot, ctDNA testing has been added into the lung cancer diagnostic process in England. The test has been added to the NHS’s National Genomic Test Directory, which means clinicians can order it for eligible patients.
If a scan suggests that a patient has advanced non-small cell lung cancer they will now be offered a ctDNA test early on, alongside the tissue biopsy. The test can usually deliver results in around two weeks.
In the past, the first MDT meeting often happened before genetic test results were available, which could delay treatment decisions. With ctDNA testing, the team is more likely to have the results in time, helping them plan the best treatment pathway without unnecessary delays.
Does ctDNA testing remove the need for a biopsy?
It is important to note that ctDNA testing does not replace the need for a tissue biopsy. A biopsy is still needed to confirm the presence, type and grade of the cancer, and to be used for genetic testing should the ctDNA fail (for example, if there is not enough cancer DNA in the blood sample).
While the processes are still being smoothed out in practice, the ultimate intent is that if the ctDNA detects a mutation, targeted treatment can be started and genetic tissue testing will no longer be needed. If the ctDNA result is inconclusive, the genetic testing can still be carried out from the tissue sample.
CtDNA testing also offers an extra layer of reassurance. In instances where a biopsy doesn’t provide enough tissue for genetic testing, or if a patient is too unwell and/or the tumour site is too difficult to access, ctDNA testing means patients can still access appropriate treatment without delay.
What are the challenges and limitations of ctDNA testing?
While some hospital trusts have been using ctDNA testing during the NHS England pilot, to others it remains new. As with any new technology, introducing or scaling up this testing will require new infrastructure, processes and training, which means there may be implementation challenges while these new systems are embedded.
Another factor to consider is the sensitivity of ctDNA testing. Not all tumours release enough DNA into the bloodstream to be detected by the test, which can lead to a false negative result. In practice, there are three scenarios on the basis of ctDNA results:
A positive ctDNA result (showing an actionable genomic alteration) provides the information needed to guide targeted treatment. Tissues genomic testing is not required
An informative negative ctDNA result means there is enough ctDNA present and no actionable genomic alternation has been found. Standard treatment can be prescribed and tissue testing is not required.
An uninformative negative ctDNA result means there is insufficient ctDNA present and does not rule out the presence of mutations, so tissue testing is still needed to be certain.
Will ctDNA testing only be carried out during diagnosis?
For now, ctDNA is only being rolled out by NHS England to support diagnosis and treatment selection. However, there is potential for it to be used in other ways in future, including monitoring the progress and status of cancer, and checking a patient’s response to treatment.
Key takeaways for patients
CtDNA testing is carried out via a blood sample, making it quicker and less invasive than a tissue biopsy.
A positive result can often guide treatment immediately.
An uninformative negative result doesn’t rule out mutations; tissue testing would still be needed.
Results are usually available within 2-3 weeks, faster than traditional tissue testing.
Key takeaways for healthcare professionals
ctDNA testing is recommended alongside tissue biopsy for advanced NSCLC.
Check your local guidelines to find out the correct sample collection and handling guidelines.
Be aware of false negatives due to low tumour DNA shedding.
Consider ctDNA results together with imaging and tissue data for treatment decisions.
The national genomic test directory outlines which tests are commissioned by the NHS in England, and which patients will be eligible for a test. Access the directory here: National genomic test directory
Scotland, Wales and Northern Ireland each have their own arrangements for requesting genomic tests. Find out more about how to request genomic testing in the devolved nations here: Genomic testing in the devolved nations
Understanding the ALEX study: what it means for patients and healthcare professionals
In this blog, Senior Clinical Research Fellow Dr Federico Monaca, explains the the results of a clinical trial based in ALK therapy regimes.
The ALEX study is one of the most influential clinical trials in the field of ALK‑positive lung cancer. It compared two targeted therapies – alectinib and crizotinib – as first‑line treatment for people with advanced ALK‑positive non‑small cell lung cancer (NSCLC).
This large, global phase III trial focused primarily on progression‑free survival, while also assessing outcomes in the brain, overall survival and safety. A total of 303 adults with stage III/IV ALK‑positive NSCLC (ECOG 0-2) took part, including individuals with asymptomatic brain metastases.
Key findings from the ALEX trial
With more than nine years of follow‑up, the results show a clear and sustained benefit for patients treated with alectinib.
Median overall survival reached 81.1 months with alectinib compared with 54.2 months for crizotinib — a 22% relative reduction in the risk of death, although the study was not powered for a formal comparison of overall survival.
Alectinib more than tripled median progression‑free survival (34.8 vs 10.9 months). The survival advantage was seen in patients with and without baseline brain metastases, reinforcing the importance of early and effective systemic and intracranial disease control.
The risk of cancer spreading or progressing in the brain was significantly lower with alectinib.
Rates of severe (grade 3–5) side effects were similar between treatment groups, but the pattern of side effects differed. Long‑term use of alectinib did not reveal unexpected safety concerns.
What do the results mean in practice?
The ALEX study firmly positions alectinib as a leading first‑line treatment option for advanced ALK‑positive NSCLC, alongside other next‑generation ALK inhibitors such as lorlatinib.
Alectinib’s predictable and generally well‑tolerated safety profile makes it particularly appealing for patients who may need treatment over many years. At the same time, its strong systemic and intracranial activity provides confidence that the disease can be controlled effectively from the outset.
Importantly, ALEX has become a benchmark for future drug development. Newer, fourth‑generation ALK inhibitors are now being tested directly against alectinib in first‑line trials, and its outcomes are frequently used as the standard against which emerging therapies are measured.
What patients need to know
For someone newly diagnosed with ALK‑positive advanced NSCLC, the ALEX results offer reassurance about what modern targeted therapy can achieve.
Alectinib can keep cancer controlled for a median of nearly three years.
Around half of patients were still alive at seven years.
It provides far stronger protection against brain metastases than older treatments like crizotinib.
Side effects are generally manageable, even with long‑term use.
In practical terms, many people can expect their cancer to be managed as a long‑term condition. Treatment discussions with an oncologist may include whether alectinib, lorlatinib or another ALK inhibitor is the best first‑line option based on individual needs and preferences.
What healthcare professionals need to know
For clinicians, ALEX reinforces alectinib’s role as a cornerstone of first‑line therapy for ALK‑positive NSCLC — particularly for patients with existing CNS involvement or those at high risk of developing brain metastases.
When choosing between available ALK inhibitors, the combination of:
prolonged progression‑free survival
strong intracranial efficacy
a well‑established safety profile
makes alectinib a compelling alternative to lorlatinib, rather than a therapy that has been superseded by it.
ALEX has also set the performance threshold for next‑generation ALK TKIs. Ongoing trials with fourth‑generation agents now use alectinib as the active comparator, and future treatment strategies will likely evolve based on how these newer drugs measure up against the ALEX standard.
