Validation of disease indicator could substantially change cancer clinical practice

Presence of tumour DNA in the blood – a biomarker or indicator of disease first identified by a BRC-supported consortium – can predict which cancer patients are most likely to relapse after having a tumour surgically removed and most likely to benefit from immunotherapy.

The findings published in Nature mean in future there could be a substantial change in cancer clinical practice, with immunotherapy only given where there is residual disease after surgery, meaning treatment would be more personalised.

Use of personalised cancer fingerprints to identify the presence of circulating tumour DNA (ctDNA) was identified as a possible biomarker of disease by the TracerX cancer research consortium in 2017 involving UCLH, the Francis Crick Institute, UCL Cancer and Cancer Research UK and led by Prof Charles Swanton of UCLH and the Crick in collaboration with industry-partners Natera.

Since development of the biomarker it has been thought that presence of ctDNA in the blood may be predictive of who will relapse post-surgery. This latest research validates this idea.

Importantly presence of ctDNA can be identified before any evidence of a relapse can be found via imaging. And it can be collected non-invasively from a single blood draw.

In the latest research, a team led by Prof Tom Powles from Barts Cancer Institute showed that ctDNA can identify which patients with urothelial carcinoma – a cancer of the urinary system – are most at risk of relapse, and who may benefit most from therapy with a monoclonal antibody called atezolizumab after surgery.

The researchers analysed results of a clinical trial published earlier this year called IMvigor010 in which some patients with urothelial cancer were given atezolizumab. The IMvigor010 trial did not find significant benefit in use of the drug. Patients in the trial had been randomly assigned either to receive atezolizumab or not.

But when researchers in this latest study analysed the findings of the IMvigor010 trial in detail, they found that presence of ctDNA soon after cancer surgery was associated with relapse, and that for patients positive for ctDNA shortly after surgery, atezolizumab improved survival rates.

The research team also reported supporting findings from a separate 2019 study called ABACUS in which atezolizumab was associated with a reduction of ctDNA levels.

More research is needed, but if the findings from the latest research are validated across tumour types, it could lead to a significant change in practice across cancer care.

TRACERx (Tracking Cancer Evolution through Therapy) is the first study to look at the evolution of cancer in real time and immense detail. Researchers are following patients all the way from diagnosis through to either disease relapse or cure after surgery, tracking and analysing how their cancer develops.