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.