While circulating tumor DNA (ctDNA) may guide adjuvant therapy in stage II-III colon cancer, detection largely hinges on systemic tumor shedding. In a secondary analysis of three prospective ctDNA studies, peritoneal metastases occurred in up to 9.4% of patients, were predominantly isolated, and were enriched among ctDNA-negative recurrences. Molecular and clinical data demonstrate reduced ctDNA levels in peritoneum-only disease, identifying a surveillance blind spot with direct implications for high-risk patients.
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