PHG Foundation has been working with the Cellular and Molecular Pathology Initiative
(CM-Path) and Cancer Research UK following a recent workshop to explore the challenges surrounding the use of liquid biopsy in medicine. One year on from our own workshop on the use of ctDNA liquid biopsy in lung cancer services, this has been a valuable opportunity to revisit this area and to consider how the pathology community will have an impact on the delivery of new technologies like liquid biopsy into the health system.
Why the focus on pathology?
Pathology is the cornerstone of the diagnosis of many diseases, particularly cancer. Pathologists play a key role in the handling, processing and analysis of patient samples to diagnose cancer, through histological, cytological or other analyses. The way cancer is diagnosed is changing however – the increasing availability of treatments targeted to tumours with specific genetic mutations means that genetic tests now form a key part of the diagnostic pathway for some cancers. This requires an integrated diagnostic approach and presents an opportunity to boost the use of molecular pathology approaches and support the implementation of innovative diagnostic approaches into healthcare.
These changes are taking place while pathology as a discipline is facing some challenges, in particular an approximate 60% decrease in the number of academic pathology posts since 2000. This matters, since a solid and extensive research base is the foundation for successful delivery of innovations into clinical practice. With an increase in the number of cellular and molecular pathology techniques available in medicine, pathology research is more important than ever.
CM-Path: a boost to academic pathology
In response to this need to boost academic pathology and innovation, the National Cancer Research Institute (NCRI) CM-Path Initiative was set up in June 2016. On 8 March CM-Path held a symposium on liquid biopsy (including analysis of circulating nucleic acids and cells), one of a series of meetings to inform and engage pathologists about innovative oncology research relevant to pathology practice. Given our mutual interest in liquid biopsy, PHG Foundation are working with CM-Path and CRUK to develop a consensus statement exploring the issues discussed at the meeting, including the promise of liquid biopsy as well as the challenges facing implementation, with a focus on the use of ctDNA testing in cancer.
The meeting highlighted key areas of research interest where liquid biopsy could have an impact. For example in metastatic breast cancer studies, ctDNA is being used to monitor patients, select therapy or detect residual disease. In lung cancer, ctDNA testing is being used to detect relapse after treatment, and circulating tumour cells are being used as a means of studying small cell lung cancer, which is currently challenging to treat as the majority of those treated with chemotherapy will relapse.
Challenges, and some progress
Several challenges that will have an impact on awareness and future implementation of liquid biopsy technologies emerged during the day's discussions, echoing the issues we highlight in our September 2017 report on ctDNA testing services in non-small cell lung cancer:
- Engagement: There is still work to be done to engage oncologists, patients and pathologists about testing, its benefits, and how it can be accessed. The multidisciplinary team (MDT), the team responsible for overseeing a patient's care, could be a means for achieving this
- Validation, logistics and procedures: There is uncertainty about the best equipment and methods to use for testing, and a need for effective communication strategies about validation studies to minimise duplication of effort
- Cost: It is not clear how test implementation should be supported and also health economic analyses are required to understand the cost implications of testing
- Ethics: Future testing has the potential to be broader in scope and carried out earlier in the patient journey, possibly as a screening test. The implications of this should be considered
This presents opportunities for the pathology community to place itself at the forefront in helping to manage these issues, not just by engaging in research but also in considering how pathology practice is changing and what pathologists can do to support the implementation of new technologies given their current expertise. The consensus statement will explore these issues in more detail.
The bigger picture
However, there is progress. It is encouraging to see that areas where we made recommendations for action – engagement via the MDT, support for test validation and clarity over funding – have been highlighted by the pathology community as important. As we reported recently, NICE have published a MedTech Innovation briefing on using ctDNA testing of EGFR in NSCLC, which is useful in terms of raising awareness of what the technology does and providing advice on how it can be used. In addition an international External Quality Assurance (EQA) exercise on ctDNA analysis, coordinated by the International Quality Network for Pathology, is ongoing and will help answer questions around the best techniques and methods to use. In the past year, NHS laboratories offering ctDNA testing have been consolidating their services by collecting data on test results and continuing engagement efforts with users.
In the meantime, there is much that we can do to raise awareness about liquid biopsy technologies among clinicians and pathologists and consider how pathology practice can support the implementation of these tests as and when they are ready for use in the clinic. The consolidation of genetic testing services in England into seven genomic laboratory hubs will significantly alter the landscape of genetics services – at this time of great change, it is vital that pathology does not get left behind.