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Statement of Translational RelevanceDetection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery to identify patients with minimal residual disease (MRD) who will ultimately recur has emerged as a potentially transformative approach in oncology. Early identification of patients with MRD through ctDNA detection could identify patients in whom additional therapy might salvage the chance of cure. To date, ctDNA MRD assays have employed a tumor-informed approach, requiring initial sequencing of tumor tissue to guide ctDNA detection, and thus cannot be used when a patient has insufficient tumor tissue for analysis. Here, we evaluate the first tumoruninformed, plasma-only ctDNA assay integrating genomic and epigenomic signatures to detect MRD in post-operative colorectal cancer (CRC) patients, without requiring parallel tumor sequencing, which produced favorable sensitivity and specificity, comparable to tumor-informed approaches. These data highlight the feasibility and potential clinical utility of plasma-only ctDNA-guided MRD detection.

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In this pilot study of five patients with rectal cancer, transanal endoscopic TME with laparoscopic assistance is feasible and safe, and is a promising alternative to open and laparoscopic TME. Evaluation of long-term functional and oncologic outcomes of this approach is needed before widespread adoption can be recommended.