A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early stage and amenable to treatment in up to half of cases, suggests a modelling study published in the open access journal BMJ Open.
Incorporating the test, formally known as a multi-cancer early detection test, or MCED for short, either yearly or biennially, could therefore improve outcomes for patients by intercepting disease progression, suggest the researchers.
Currently, only a few cancers can be reliably screened for-those of the breast, bowel, cervix (neck of the womb), and lung for those at high risk. While effective at lowering death rates from these diseases, these screens can also result in false positive results and overdiagnosis, say the researchers.
The optimal interval at which screening will pick up the most cancers at an early stage (I and II) while at the same time avoiding unnecessary testing and treatment still isn’t clear.
To inform future clinical trials, the researchers drew on a previously published disease progression model for many different cancers. They used this to predict the impact of regular screening with an MCED test on the time of cancer diagnosis and patient death for different screening schedules among 50-79 year olds in receipt of usual care.
The screening schedules modelled ranged from 6 months to 3 years, but with an emphasis on annual and biennial screening for two sets of cancer growth scenarios. These were ‘fast’, where tumours remain at stage I for between 2 and 4 years before progressing; and ‘fast aggressive’ where tumours remain at stage 1 for between 1 and 2 years, with decreasing periods of time for progression to successive stages.
Cancer types included were those of the anus; bladder; breast; cervix; bowel/rectum; food pipe (oesophagus); gallbladder; head and neck; kidney; liver/ bile-duct; lung; ovary; pancreas; prostate; sarcoma (soft tissues/bone); stomach; thyroid; urothelial tract, and uterus, as well as leukaemia, lymphoma, melanoma, blood cancers (myeloid neoplasm, immune cell cancers (plasma cell neoplasm).
The researchers drew on MCED test characteristics from a recently published report and patient outcomes from population cancer data from the US Surveillance, Epidemiology and End Results (SEER) programme.
Their analysis showed that all MCED screening intervals had more favourable early-stage diagnostic rates than usual care alone. There was a larger impact on stage shift for tumours with ‘fast’ growth than for tumours with ‘fast aggressive’ growth.
But annual MCED screening under the fast tumour growth scenario was associated with a higher number of diagnoses: 370 more cancer signals were detected per year per 100,000 people screened, with 49% fewer late-stage diagnoses, and 21% fewer deaths within 5 years than usual care.
While biennial MCED screening was able to shift the stage at diagnosis and avert deaths, it was not as effective as annual screening: 292 more cancer signals were detected/year/100,000 people screened; 39% fewer late-stage diagnoses; and 17% fewer deaths within 5 years than usual care.
Annual MCED screening prevented more deaths within 5 years than biennial screening for the fast tumour growth scenario. But biennial screening had a higher positive predictive value: 54% compared with 43%. In other words ,it picked up more cancers for each completed test.
And it was more efficient at preventing more deaths within 5 years per 100,000 tests-132 compared with 84, although it prevented fewer deaths per year, so was less effective.
Given that 392 people are diagnosed each year with an aggressive cancer that would kill them within 5 years, earlier diagnosis through biennial MCED screening could have averted 54 (14%) of these deaths. But annual MCED screening could have avoided 84 (21%) fewer deaths, say the researchers.
“Based on the performance characteristics from a case control study, both annual and biennial screening with an MCED test have the potential to intercept 31–49% of cancers at stage I-II that would otherwise present at stage III-IV,” they estimate.
“Of these, approximately equal numbers would be detected at stage I and at stage II: 14% stage I and 16% stage II to 23% stage I and 26% stage II.”
The researchers acknowledge that their estimates assume 100% compliance with the recommended screening schedule and 100% accuracy of confirmatory follow up tests, and so represent the upper bounds of potential benefits of MCED cancer screening.
It is also assumed that a reduction in the number of late-stage cancer diagnoses would automatically reduce death rates from the disease. And they point out: “The optimal choice of screening interval will depend on assessments of real-world cancer survival and the costs of confirmatory testing after MCED screening.
“However, both annual and biennial MCED screening intervals have the potential to avert deaths associated with late-stage cancers when used in addition to current guideline-based cancer screening.”
Rous, B., et al. (2025). Assessment of the impact of multi-cancer early detection test screening intervals on late-stage cancer at diagnosis and mortality using a state-transition model. BMJ Open. doi.org/10.1136/bmjopen-2024-086648.
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