Are Non-invasive Multi-cancer Early Cancer Detection Tests the Future?

Current cancer screening methods are effective for detecting early stage cancers and even preventing some cancers, but their effectiveness has only been demonstrated for a handful of cancers, and for many cancers, there are no screening tests clinically available. In addition, the majority of the screening methods are not ideal, resulting in suboptimal compliance and the occurrence of preventable cancers. A screening test that is convenient, safe, accurate and that can screen for multiple cancers is an ideal screening test that would address many of the shortcomings of the current tests. Multi-cancer detection tests (MCD) have the potential to meet these challenges and have engendered substantial enthusiasm in light of this. Using advances in DNA sequencing technology, cancer epigenetics and artificial intelligence, they are able to detect a large number of cancers predominantly via the patterns of methylated DNA alterations, DNA sequence alterations, and DNA fragment patterns of cell free DNA in the plasma and can accurately distinguish the cancer site of origin. Of note, some of the tests also combine circulating free DNA (cfDNA) with protein-based markers. However, for the majority of early stage cancers, the sensitivity is modest and below that of most of the current standard of care cancer screening tests. Furthermore, the clinical utility of screening for many of the cancers detectable by MCD tests remains to be proven. Here we describe the features of MCD tests, review the current data supporting their potential to be used in the clinic for cancer screening, and discuss the knowledge gaps surrounding understanding their clinical utility, with a focus on GI cancer screening.