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<p>Recurrence after curative-intent surgery for colorectal cancer is a major cause of cancer-related death. Circulating cell-free tumor DNA (ctDNA) is increasingly used in the perioperative setting to detect residual disease. However, the association between preoperative ctDNA, the tumor microenvironment, including tumor-infiltrating lymphocytes, and recurrence is unknown. We explored the association between ctDNA and the tumor microenvironment in patients with non-metastatic CRC undergoing curative-intent surgery. ctDNA was assessed using a tumor-agnostic hypermethylated cfDNA test. Among 140 patients, ctDNA tested positive in 102 (72.9%) before surgery, with 38 (27.1%) tumors classified as immune infiltration high. ctDNA was associated with expression of cancer-metastasis pathways, while immune active phenotypes were associated with immune infiltration high tumors. ctDNA status could identify deficient mismatch repair tumors with an active immune phenotype. The results suggest that a positive ctDNA analysis before surgery is associated with a metastatic tumor microenvironment.</p>

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Preoperative positive ctDNA analysis is associated with the tumor microenvironment, and the risk of recurrence in non-metastatic colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月21日

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  • Mikail Gögenur,
  • Lukas Balsevicius,
  • Sarah Østrup Jensen,
  • Nadia Øgaard,
  • Iben Lyskjær,
  • Tobias Freyberg Justesen,
  • Michael Bzorek,
  • Anne-Marie Kanstrup Fiehn,
  • Line Rosell Walker,
  • Rasmus Dahlin Bojesen,
  • Andreas Weinberger Rosen,
  • Claus Lindbjerg Andersen,
  • Ismail Gögenur

摘要

Recurrence after curative-intent surgery for colorectal cancer is a major cause of cancer-related death. Circulating cell-free tumor DNA (ctDNA) is increasingly used in the perioperative setting to detect residual disease. However, the association between preoperative ctDNA, the tumor microenvironment, including tumor-infiltrating lymphocytes, and recurrence is unknown. We explored the association between ctDNA and the tumor microenvironment in patients with non-metastatic CRC undergoing curative-intent surgery. ctDNA was assessed using a tumor-agnostic hypermethylated cfDNA test. Among 140 patients, ctDNA tested positive in 102 (72.9%) before surgery, with 38 (27.1%) tumors classified as immune infiltration high. ctDNA was associated with expression of cancer-metastasis pathways, while immune active phenotypes were associated with immune infiltration high tumors. ctDNA status could identify deficient mismatch repair tumors with an active immune phenotype. The results suggest that a positive ctDNA analysis before surgery is associated with a metastatic tumor microenvironment.