Minimal Residual Disease Detection After Cancer Treatment Cannot Reliably Guide Therapy Decisions

After cancer surgery or chemotherapy, tiny amounts of remaining cancer (minimal residual disease or MRD) often recur months to years later. ctDNA blood tests can detect MRD, but sensitivity varies by cancer type, and it's unclear whether MRD-guided treatment decisions improve outcomes compared to standard protocols.

Circulating tumor DNA (ctDNA) can detect MRD at levels as low as 0.01% variant allele frequency using tumor-informed approaches (Signatera by Natera, RaDaR by Inivata). However, sensitivity varies: ~90% for colorectal cancer but only 50-70% for early-stage breast and lung cancers where tumor shedding is lower. Randomized trials are underway testing MRD-guided adjuvant therapy (DYNAMIC, circulate, BESPOKE CRC) but results are mixed. The key question: should MRD-negative patients skip chemotherapy? The risk of false negatives means some cancers would be missed.

Why It Matters

~50% of cancer patients who undergo curative-intent surgery will experience recurrence. Adjuvant chemotherapy is given to ~1M+ cancer patients/year in the US, but only 3-5% actually benefit (the rest are cured by surgery alone or will recur regardless). MRD testing could spare hundreds of thousands from unnecessary chemo while ensuring those who need it get it.

Startup Approach

Develop ultra-sensitive MRD detection platform combining ctDNA with ctRNA, exosome analysis, and immune signatures to achieve >95% sensitivity across cancer types. Or build a clinical decision support platform that integrates MRD results with tumor genomics, imaging, and patient factors to generate personalized treatment recommendations.

NIH Funding

NCI funds MRD research through NCTN (National Clinical Trials Network). NCI Cancer Moonshot supports early detection technologies. NCTN trials (DYNAMIC, BESPOKE) are NIH-supported.

Who's Working On It

Natera (Signatera MRD test), Guardant Health (Guardant Reveal), Foundation Medicine/Roche, NeoGenomics, Inivata (RaDaR)