ctDNA:progress on streamlining cancer diagnosis

In a world first, the NHS has announced it is rolling out ‘blood-test first’ testing for patients with non-small cell lung cancer (NSCLC) in England. The tests have been added to the Genomic Test Directory and hold great potential for streamlining cancer diagnosis and treatment pathways.

What is circulating tumor DNA testing?

A sample of blood is collected, and the test is used to detect fragments of DNA, known as circulating tumour DNA (ctDNA), that break off from tumours, and make their way into the bloodstream. These fragments can be used to more accurately diagnose NSCLC in a shorter time than current methods.

Why is ctDNA testing important?

Traditional tissue biopsies for diagnosis can be difficult to perform and present risks to patients, particularly those who are very unwell. Up to 30,000 patients per year have genomic testing performed on their tissue biopsies, which can provide invaluable information about mutations that could negatively affect treatment success and enable patients to begin targeted therapy more rapidly. Unfortunately, the turnaround time from test to treatment can be several weeks – a timeline that can impact treatment success. The ’blood-test first’ approach using ctDNA can reduce these turnaround times and provide a much more accessible and less invasive method of examining a tumour.

Additionally, the genetics of a tumour are not always the same throughout the whole mass. Tissue biopsies have limited power to detect these differences but ctDNA blood testing can potentially provide a much more detailed understanding of the tumour. By using a more detailed method patients may benefit from personalised treatment pathways that consider these genetic differences and enable more rapid responses to changes in tumour characteristics.

An independent health economic analysis has estimated that this new test could save the NHS up to £11 million per year in lung cancer care. Following pilot testing via the North Thames Genomic Medicine Service and collaborators which saw around 10,000 patients receive the test, it has now been rolled out across the country in what is being heralded as a ‘step-change’ in cancer care. Professor Dame Sue Hill, Chief Scientific Officer for England, sees this test as ‘a great example of the NHS harnessing the power of genomic technological advances to enable the latest groundbreaking treatment to be delivered to patients’.

Are there any considerations for implementation?

Looking ahead there are several questions to be addressed to provide further clarity around this exciting new development:

• Who is eligible for the test?
  • Currently particular patients with radiologically suspected stage III/IV lung cancer or patients with a new histological diagnosis of NSCLC where diagnostic molecular testing has failed are eligible for the test
  • It is unclear how many patients this encompasses and if there are plans to expand testing to patients outside of these criteria.
  • Patients at earlier disease stages may benefit from the prognostic abilities of ctDNA testing.
  • Detection of minimal residual disease (MRD) by ctDNA testing following treatment with curative intent could identify disease recurrence earlier along with informing decisions about the need for adjuvant chemotherapy.
• What does this mean for NHS staff?
  • More testing requires more time for dealing with the results – do clinicians have the capacity for this?
  • Will all eligible patients be able to access testing?
  • Does engagement and understanding among staff need to be supported?
• Long-term clinical utility needs to be demonstrated
  • The use of ctDNA blood tests have been shown to speed up time to treatment and enable targeted therapy, but long-term outcome studies will be needed to demonstrate overall patient outcomes are improved.

The NHS is the first health system in the world to roll out this ctDNA approach. Whilst national implementation may present with some challenges such as capacity, accessibility and engagement, the proposed benefits will be transformative for patient care. There is considerable research and development activity regarding ctDNA and hundreds of clinical trials investigating its use in different cancers. Whilst the ‘high burden’ cancers such as colorectal, NSCLC and breast cancer are investigating ctDNA uses at pace,  there is a growing body of evidence and increasing momentum for the use of ctDNA in other areas such including lymphomas, gastroesophageal, gynaecological and hepatocellular cancers.   We look forward to the announcements of further developments and the realisation of this being expanded to more cancer types and patients.