The effect of surgical trauma on circulating free DNA levels in cancer patients-implications for studies of circulating tumor DNA

Mol Oncol. 2020 Aug;14(8):1670-1679. doi: 10.1002/1878-0261.12729. Epub 2020 Jun 16.


Detection of circulating tumor DNA (ctDNA) post-treatment is an emerging marker of residual disease. ctDNA constitutes only a minor fraction of the cell-free DNA (cfDNA) circulating in cancer patients, complicating ctDNA detection. This is exacerbated by trauma-induced cfDNA. To guide optimal blood sample timing, we investigated the duration and magnitude of surgical trauma-induced cfDNA in patients with colorectal or bladder cancer. DNA levels were quantified in paired plasma samples collected before and up to 6 weeks after surgery from 436 patients with colorectal cancer and 47 patients with muscle-invasive bladder cancer. To assess whether trauma-induced cfDNA fragments are longer than ordinary cfDNA fragments, the concentration of short (< 1 kb) and long (> 1 kb) fragments was determined for 91 patients. Previously reported ctDNA data from 91 patients with colorectal cancer and 47 patients with bladder cancer were used to assess how trauma-induced DNA affects ctDNA detection. The total cfDNA level increased postoperatively-both in patients with colorectal cancer (mean threefold) and bladder cancer (mean eightfold). The DNA levels were significantly increased up to 4 weeks after surgery in both patient cohorts (P = 0.0005 and P ≤ 0.0001). The concentration of short, but not long, cfDNA fragments increased postoperatively. Of 25 patients with radiological relapse, eight were ctDNA-positive and 17 were ctDNA-negative in the period with trauma-induced DNA. Analysis of longitudinal samples revealed that five of the negative patients became positive shortly after the release of trauma-induced cfDNA had ceased. In conclusion, surgery was associated with elevated cfDNA levels, persisting up to 4 weeks, which may have masked ctDNA in relapse patients. Trauma-induced cfDNA was of similar size to ordinary cfDNA. To mitigate the impact of trauma-induced cfDNA on ctDNA detection, it is recommended that a second blood sample collected after week 4 is analyzed for patients initially ctDNA negative.

Keywords: bladder cancer; cell-free DNA; circulating tumor DNA; colorectal cancer; trauma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Circulating Tumor DNA / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / surgery*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Wounds and Injuries / blood*


  • Circulating Tumor DNA