Molecular residual disease: Charting a new path for treating resectable solid tumors

Molecular residual disease (MRD), detected via circulating tumor DNA (ctDNA) after curative-intent surgery, identifies resectable solid tumor patients at high recurrence risk, thereby enabling enriched trials with larger effect sizes and smaller samples. Yet enrichment narrows the eligible population and thus challenges conventional randomized designs. We propose an MRD Registry as an external control cohort that integrates quantitative ctDNA data with outcomes to validate ctDNA dynamics as response indicators-facilitating efficient MRD-based trial design and accelerating novel therapy development.