Cancer DNA is detectable in blood years before diagnosis

Some thoughts on this as someone working on circulating-tumor DNA for the last decade or so:

- Sure, cancer can develop years before diagnosis. Pre-cancerous clones harboring somatic mutations can exist for decades before transformation into malignant disease.

- The eternal challenge in ctDNA is achieving a "useful" sensitivity and specificity. For example, imagine you take some of your blood, extract the DNA floating in the plasma, hybrid-capture enrich for DNA in cancer driver genes, sequence super deep, call variants, do some filtering to remove noise and whatnot, and then you find some low allelic fraction mutations in TP53. What can you do about this? I don't know. Many of us have background somatic mutations speckled throughout our body as we age. Over age ~50, most of us are liable to have some kind of pre-cancerous clones in the esophagus, prostate, or blood (due to CHIP). Many of the popular MCED tests (e.g. Grail's Galleri) use signals other than mutations (e.g. methylation status) to improve this sensitivity / specificity profile, but I'm not convinced its actually good enough to be useful at the population level.

- The cost-effectiveness of most follow on screening is not viable for the given sensitivity-specificity profile of MCED assays (Grail would disagree). To achieve this, we would need things like downstream screening to be drastically cheaper, or possibly a tiered non-invasive screening strategy with increasing specificity to be viable (e.g. Harbinger Health).

I guess the problem is a mismatch between detection capability and treatment capability? We seem to be getting increasingly good at detecting precancerous states but we don't have corresponding precancer treatments, just the regular cancer treatments like chemo or surgery which are a big hit to quality of life, expensive, harmful etc.

Like if we had some kind of prophylactic cancer treatment that was easy/cheap/safe enough to recommend to people even on mild suspicion of cancer with false positives, we could offer it to positive tests. Maybe even just lifestyle interventions if those are proven to work. That's probably very difficult though, just dreaming out loud.