anchor Nakamura Y, Watanabe J, Akazawa N, et al. "ctDNA-based molecular residual disease and survival in resectable colorectal cancer" (the CIRCULATE-Japan GALAXY observational study). Nat Med. 2024;30(11):3272-3283. A large prospective multicenter observational registry (n=2,240; stage II-III colon cancer and stage IV colorectal cancer undergoing curative-intent resection) measuring tumor-informed ctDNA across the molecular-residual-disease (MRD) window and during/after adjuvant chemotherapy. ctDNA positivity in the MRD window was associated with markedly inferior disease-free and overall survival, and sustained versus transient ctDNA clearance under adjuvant chemotherapy stratified outcomes. The principal observational evidence in the sub-topic's trial spine complementing the DYNAMIC randomized trial: it characterizes the prognostic and predictive behavior of ctDNA/MRD that motivates ctDNA-guided escalation (on positivity) and de-escalation (on sustained clearance/negativity) of adjuvant therapy. Note the population is broader than resected stage II colon cancer (it includes stage III and stage IV); its bearing on the sub-topic's stage II question is via the MRD biology it establishes, not a stage II-specific randomized comparison.

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