January 9, 2024

expert reaction to novel proteomics-based plasma test for early detection of multiple cancers

A study published in BMJ Oncology looks at proteomic-based plasma test for early detection of multiple cancers. 

Professor Richard Sullivan, Director at the Institute of Cancer Policy and Co-Director of the Centre for Conflict & Health Research at King’s College London, said:

“There is a lot of hype around multi-cancer early detection tests (MCEDs), and multiple companies and platforms are entering this market. However, the clinical utility of this technology, whether for routine symptomatic patient assessment or screening, is a very long way from being proven.

“The hurdles for this technology delivering clinically meaningful benefits are so significant that this entire approach to early detection and screening may fail. Rigorous clinical evaluation is needed. The results presented in this study are very preliminary and a great deal more research will be needed to know whether this has any applicability in the real world of cancer care.”

Dr Thomas Round, General Practitioner and Academic Clinical Research Fellow at King’s College London, said:

“Early detection is a key objective for improving cancer outcomes, and there is a lot of interest in multi-cancer early detection (MCED) tests in screening for cancer signals before symptoms develop.

“This new paper reports the use of a form of MCED, testing plasma proteins rather than cell-free DNA. This is an interesting approach, though there are some limitations for this paper, such as the relatively small sample size of 440 for this observational study.

“There needs to be further larger scale research, both observational and ideally a randomised trial into this specific test, including in different populations before the authors assert there can be ‘integration into healthcare system and eventual inclusion into check ups’. While this is interesting work in the rapidly developing field of MCED tests, this study shows the need for further trials in the area of early cancer detection.”

Dr Mangesh Thorat, Honorary Senior Lecturer, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, Queen Mary University of London​, said:

“Rapid technological improvements have made multiple cancer early detection (MCED) tests a realistic possibility with several such assays in various stages of development and evaluation. This preliminary, essentially a proof-of-concept study without any external validation data, presents one such assay based on plasma protein levels. Many questions like biological underpinning of the assay as well as the design and replication of the assay in much needed future studies remain unanswered. However, the interesting aspects of this assay are a much higher sensitivity for stage I cancers than other similar assays in development and gender-specific performance differences which are biologically and clinically relevant. If the assay performance in future well-designed sequential studies is anywhere close to what this preliminary study suggests, then it could really be a game changer.”

Professor Stephen W. Duffy, Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, said:

“This paper provides results for a proteomic based plasma test in discriminating 18 types of cancer in 396 patients from 44 healthy subjects. The results suggest good sensitivity, including to early stage cancers, and low false positive rates. Identification of the site of tumour origin was less accurate, but nevertheless impressive. However, there are two major caveats. The first is the small number of cancers of any specific type, and the even smaller number of stage I cancers. Of the 396 tumours, only 25% were at stage I, so there is considerable uncertainty around the finding of good accuracy for early stage disease. The second and more important reservation is that the modelling which produces tests like this can involve overfitting and therefore overestimation of accuracy. Before making any firm conclusions about the quality of this test, it is essential to see its performance on an independent set of cancers and healthy subjects.”

Professor Paul Pharoah, Professor of Cancer Epidemiology, Department of Computational Biomedicine, Cedars-Sinai Medical Center, said:

“Simple blood tests that can detect many different cancers in the early stages (test is sensitive) and do not generate false positives (test is specific) are a holy grail for early detection.  Many such tests have been developed or are in development.  This paper reports on the initial results of the development of one such test.  While the results show some promise, it is far too soon to be confident that this test will turn out to be useful for early cancer detection. 

“The researchers own summary of their findings is “this study serves as a proof of concept for the potential utility of proteomic analysis in the early detection of various cancers” and “It is important to note that this study represents an initial exploration into the field of proteomics-based cancer detection, and further validation in larger population cohorts is necessary to establish the reliability and generalisability of our findings”.  In other words, these sort of tests might be useful, but much more data are needed to say one way or the other.

“There are some basic scientific reasons that limit the interpretation of these results.  First, the number of samples used in the study is very small and so the results will not be statistically robust.  Second, the same samples that were used to develop the test were used to evaluate the accuracy of the test.  This will guarantee that the test does well.  The test must be evaluated in completely independent samples before it is possible to say anything definitive about how accurate it is.”

‘Novel proteomics-based plasma test for early detection of multiple cancers in the general population’ by Bogdan Budnik et al. was published in BMJ Oncology at 23:30 UK time on Tuesday 9th January.

DOI: 10.1136/bmjonc-2023-000073

Declared interests

Prof Pharoah: No conflicts of interest.

Prof Duffy: No conflicts of interest.

Dr Thorat: Dr. Thorat previously served as the Deputy Director (Clinical) for Cancer Prevention Trials Unit (KCL) which is involved in NHS Galleri trial. Dr. Thorat has not had any involvement in this trial.

For all other experts, no reply to our request for DOIs was received.