Lung cancer test predicts survival in early stages better than current methods

Researchers at UCLH, the Francis Crick Institute, and the UCL Cancer Institute have shown that a test called ORACLE can predict lung cancer survival at the point of diagnosis better than currently used clinical risk factors. This could help doctors make more informed treatment decisions for people with stage 1 lung cancer, potentially reducing the risk of the cancer returning or spreading.

The ORACLE test involves taking a tumour sample via biopsy, then analysing the tumour for the presence of a specific set of 23 genes, known to predict lung cancer mortality. This analysis looks at how ‘strongly’ each of these genes is expressed in the tumour, then generates a numerical risk score, to represent the risk of the tumour spreading.

If introduced in clinical practice, this risk score would be considered alongside other risk factors, such as tumour stage, to help guide oncologists and patients make better informed decisions around surveillance and the use of chemotherapy.

The biopsy procedure for patients would be the same as current practice. But use of the new ORACLE test using the biopsy sample would improve risk prediction.

For the research, published in Nature Cancer, and supported by the BRC, the team tested ORACLE in 158 people with lung cancer as part of the Cancer Research UK-funded TRACERx study. They found that ORACLE could better predict patient survival than currently used clinical standards like tumour stage.

ORACLE was developed in 2019 in research by the TRACERx consortium – a collaboration involving UCLH – to overcome the lack of biological markers in lung cancer, which can indicate to doctors who might be at a greater risk of their cancer coming back or spreading to another part of the body.

This is particularly important for people with stage 1 lung cancer, who are normally given surgery without chemotherapy. For a quarter of stage 1 patients, their cancer returns, suggesting they may have benefitted from more frequent monitoring or chemotherapy.

In current practice, when doctors take a sample from a tumour, they typically only capture less than 1% of the tumour. This means they may miss signs of risk present in other parts of the tumour.

ORACLE overcomes this by looking at genes that are expressed in all parts of the tumour, which are predictive of risk.

The next steps for the researchers are to compare people with high ORACLE scores receiving standard care and those receiving more surveillance or chemotherapy to determine if the test improves survival, even for people diagnosed at the earliest stage.

Prof Charles Swanton, medical oncologist at UCLH, Principal Group Leader of the Cancer Evolution and Genome Instability Laboratory at the Crick, Chair in Personalised Cancer Medicine at the UCL Cancer Institute, and Chief Investigator of the CRUK TRACERx study, said: “Lung cancer is the leading cause of cancer-related death throughout the world, so it’s clear we need better markers to accurately classify tumours and predict who is at high risk. We’re now working with the Translation team at the Crick and industry partners to progress ORACLE into a test which could hopefully be used in the clinic as soon as possible.