Research

Hype or hope? Screening test promises early detection for haematological cancers


A blood test for circulating cell-free DNA (cfDNA) may offer early detection screening for most types of cancer, but the predictions have been met with scepticism from some cancer specialists.

In a paper published in Annals of Oncology, US researchers said the results obtained with their multi-cancer early detection (MCED) test showed it was accurate enough to be rolled out for population screening.

The test, developed and marketed by healthcare company GRAIL uses cell-free DNA (cfDNA) sequencing in combination with machine learning to detect cancer signals across multiple cancer types and predict cancer signal origin (CSO).

In a validation study involving 2823 people with cancer and 1254 people without cancer the specificity for cancer signal detection was reported as 99.5% and sensitivity was 51.5%. Overall accuracy of cancer signal origin prediction in true positives was 88.7%.

Overall sensitivity for hematologic malignancies was 55.1%, and the sensitivity of cancer signal origin prediction was 52.4% for lymphoid cancers and 72.3% for plasma cell neoplasms.

The sensitivity of the test increased with stage, ranging from 16.8% for stage I through 40.4%  for stage II, 77.0% for stage III and 90.1% for stage IV cancers.

The researchers said the test could detect cancer signals across more 50 cancer types and its Stage I-III sensitivity was 67.6% for 12 cancers that accounted for two-thirds of cancer deaths in the US (anal, bladder, bowel, oesophageal, stomach, head and neck, liver and bile duct, lung, ovarian and pancreatic cancers, lymphoma and cancers of white blood cells such as multiple myeloma).


If used in population screening, the researchers estimated the tests’ positive predictive value (PPV) as 44.4% among people most likely to develop cancer, those aged 50-79, and the negative predictive value (NPV) was 99.4%.

“Taken together, these results demonstrate that this targeted methylation-based MCED test has high specificity that is generalizable across study populations, detects cancer signals across a broad range of cancer types with diverse biologic features (including those that currently lack screening tests), and provides accurate CSO prediction that may inform patient management,” they concluded.

“These results support that this blood-based MCED test may complement existing single-cancer screening tests and result in reduced cancer mortality.”

However, the response from cancer researchers and oncologists has been sceptical, with many warning that population screening with the test would be costly and lead to overinvestigation and overtreatment.

Prof Paul Pharoah, Professor of Cancer Epidemiology, University of Cambridge, said the only valid way to evaluate the performance of a screening test is by randomised controlled trial, with real endpoints such as mortality.

“Who is going to bear the cost of the investigation of individuals with a positive test many of whom will not have a detectable cancer?” he said.

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